| |
Important Note: The following information
is provided for your education. It should not be relied upon
for personal diagnosis or treatment. If you believe that a particular
therapy applies to you or someone you care about, be sure to
consult a doctor before trying it.
ADHD Research: 2002-2006
J Child Adolesc Psychopharmacol. 2006 Oct;16(5):611-9.
Atomoxetine for Attention-Deficit/Hyperactivity Disorder Symptoms
in Children with Pervasive Developmental Disorders: APilot Study.
Troost PW, Steenhuis MP, Tuynman-Qua HG, Kalverdijk LJ, Buitelaar JK, Minderaa
RB, Hoekstra PJ.
Department of Psychiatry, University Medical Center Groningen, University of
Groningen, The Netherlands.
Objective: This pilot study examined the effects of atomoxetine on
attention-deficit/hyperactivity disorder (ADHD) symptoms and autistic features
in children with pervasive developmental disorders (PDD). Method: Twelve
children (aged 6-14 years) with PDD accompanied by ADHD symptoms entered a
10-week open-label study with atomoxetine (1.19 +/- 0.41 mg/kg/day). Response
was assessed by using parent and clinician rating scales with change in the
ADHD-Rating Scale (ADHDRS) as primary outcome measure. Results: Atomoxetine
reduced ADHD-symptoms as measured by the ADHDRS (44% decrease vs. baseline, p <
0.003), the Conners' Parent Rating Scale-R:S (CPRS-R) (25% in the subscale
"Cognitive Problems," p < 0.028; 32% in "Hyperactivity," p < 0.030; and 23% in
"ADHD index," p < 0.023). We found a reduction of 21% (p = 0.071) for changes in
the subscale "Hyperactivity" of the Aberrant Behavior Checklist (ABC). No change
was found in any of the other ABC subscales, nor in the subscale "Oppositional"
of the CPRS-R. Five patients (42%) discontinued because of side effects.
Gastrointestinal symptoms, irritability, sleep problems, and fatigue were the
most frequent side effects. Conclusions: These preliminary findings indicate
that atomoxetine may be a promising new agent in the treatment of ADHD symptoms
in children with PDD. However, children with PDD may have a higher vulnerability
for some of the known side-effects of atomoxetine.
-----
J Child Adolesc Psychopharmacol. 2006 Oct;16(5):599-610.
Open-label atomoxetine for attention-deficit/ hyperactivity
disorder symptoms associated with high-functioning pervasive developmental
disorders.
Posey DJ, Wiegand RE, Wilkerson J, Maynard M, Stigler KA, McDougle CJ.
Department of Psychiatry and Christian Sarkine Autism Treatment Center at the
Indiana University School of Medicine, Indianapolis, Indiana.
Objective: The aim of this study was to conduct an initial evaluation of the
efficacy of atomoxetine for attention-deficit/hyperactivity disorder (ADHD)
symptoms in children with pervasive developmental disorders (PDDs). Method:
Children with PDDs and a nonverbal IQ of >/=70 received atomoxetine (target dose
1.2-1.4 mg/kg/day) during the course of an 8-week, open-label, prospective
study. Standardized assessments of efficacy and tolerability were collected at
regular intervals during the trial. Results: Sixteen children and adolescents
(mean age 7.7 +/- 2.2 years, age range 6-14 years) with autistic disorder (n =
7), Asperger's disorder (n = 7), or PDD not otherwise specified (n = 2) received
atomoxetine (mean dose 1.2 +/- 0.3 mg/kg/day). Twelve participants (75%) were
rated as "much" or "very much improved" on the Clinical Global
Impressions-Improvement scale. The most significant improvement was seen in the
area of ADHD symptoms as measured by the SNAP-IV and Aberrant Behavior Checklist
(effect size = 1.0-1.9). Improvements of lesser magnitude (effect size =
0.4-1.1) were seen in irritability, social withdrawal, stereotypy, and
repetitive speech. There were no significant changes on the Conners' Continuous
Performance Test. Atomoxetine was well tolerated with the exception of 2
participants (13 %) who stopped medication due to irritability. Weight decreased
by a mean of 0.8 kg during the 8-week trial. Conclusions: Placebo-controlled
studies are indicated to determine atomoxetine's efficacy for ADHD symptoms in
PDDs.
-----
J Child Adolesc Psychopharmacol. 2006 Oct;16(5):549-560.
Clinical Effects and Adverse Reactions of Off-Label Use of
Aripiprazole in Children and Adolescents with Developmental Disabilities.
Valicenti-McDermott MR, Demb H.
Children's Evaluation and Rehabilitation Center, R.F. Kennedy Center of
Excellence in Developmental Disabilities, Albert Einstein College of Medicine,
Bronx, New York.
Objective: The aim of this study was to report on the clinical efficacy and side
effects of aripiprazole in treating behavioral symptoms of children with a
developmental disability (DDs). Design/methods: A retrospective chart review of
the first 32 children treated with aripiprazole at an urban clinic for children
with DD was conducted. Results: Ages ranged from 5 to 19 years; 9 (28%) were
female. Twenty four had diagnoses within the autistic spectrum and 18 had mental
retardation (MR). Other disorders included: attention-deficit/hyperactivity
disorder/disruptive behavior disorders (n = 13), mood disorders (n = 7),
reactive attachment (n = 2), and sleep disorders (n = 2). Target symptoms
included aggression, hyperactivity, impulsivity and, self-injurious behaviors.
Twenty eight of the children were switched from another antipsychotic. The mean
daily aripiprazole starting dose was 7.1 +/- 0.32 mg (0.17 mg/kg/day) and the
mean daily maintenance dose was 10.55 +/- 6.9 mg (0.27mg/kg/day). Aripiprazole
had been used for a period between 6 and 15 months. Improvement in target
symptoms was found in 56%. When treating a child with MR, the concomitant
presence of an autistic spectrum diagnosis predicted a worse outcome. Side
effects were reported in 16 (50%), with the most frequent being sleepiness (n =
6). Mean body mass index (BMI) rose from 22.5 to 24.1 (p = 0.003) over the
follow up period, with changes in the BMI z scores. These changes were more
pronounced in children younger than 12 years. Conclusions: These results with
aripiprazole in this difficult-to-treat population suggest that this medication
warrants controlled studies of its effectiveness and safety.
-----
J Nutr Health Aging. 2006;10(5):377-385.
Effects of Nutrients (in Food) on the Structure and Function of
the Nervous System: Update on Dietary Requirements for Brain. Part 1:
Micronutrients.
Bourre JM.
J.M. Bourre, Member of the French Academy of Medicine. INSERM, U705 ; CNRS, UMR
7157 ; Universites Paris 7 et 5, Department of Neuro-pharmaco-nutrition. Hopital
Fernand Widal, 200, rue du Faubourg Saint-Denis, 75475 Paris cedex 10. Mail :
jean-marie.bourre@fwidal.inserm.fr.
The objective of this update is to give an overview of the effects of dietary
nutrients on the structure and certain functions of the brain. As any other
organ, the brain is elaborated from substances present in the diet (sometimes
exclusively, for vitamins, minerals, essential amino-acids and essential fatty
acids, including omega- 3 polyunsaturated fatty acids). However, for long it was
not fully accepted that food can have an influence on brain structure, and thus
on its function, including cognitive and intellectuals. In fact, most
micronutrients (vitamins and trace-elements) have been directly evaluated in the
setting of cerebral functioning. For instance, to produce energy, the use of
glucose by nervous tissue implies the presence of vitamin B1; this vitamin
modulates cognitive performance, especially in the elderly. Vitamin B9 preserves
brain during its development and memory during ageing. Vitamin B6 is likely to
benefit in treating premenstrual depression. Vitamins B6 and B12, among others,
are directly involved in the synthesis of some neurotransmitters. Vitamin B12
delays the onset of signs of dementia (and blood abnormalities), provided it is
administered in a precise clinical timing window, before the onset of the first
symptoms. Supplementation with cobalamin improves cerebral and cognitive
functions in the elderly; it frequently improves the functioning of factors
related to the frontal lobe, as well as the language function of those with
cognitive disorders. Adolescents who have a borderline level of vitamin B12
develop signs of cognitive changes. In the brain, the nerve endings contain the
highest concentrations of vitamin C in the human body (after the suprarenal
glands). Vitamin D (or certain of its analogues) could be of interest in the
prevention of various aspects of neurodegenerative or neuroimmune diseases.
Among the various vitamin E components (tocopherols and tocotrienols), only
alpha-tocopherol is actively uptaken by the brain and is directly involved in
nervous membranes protection. Even vitamin K has been involved in nervous tissue
biochemistry. Iron is necessary to ensure oxygenation and to produce energy in
the cerebral parenchyma (via cytochrome oxidase), and for the synthesis of
neurotransmitters and myelin; iron deficiency is found in children with
attention-deficit/hyperactivity disorder. Iron concentrations in the umbilical
artery are critical during the development of the foetus, and in relation with
the IQ in the child; infantile anaemia with its associated iron deficiency is
linked to perturbation of the development of cognitive functions. Iron
deficiency anaemia is common, particularly in women, and is associated, for
instance, with apathy, depression and rapid fatigue when exercising. Lithium
importance, at least in psychiatry, is known for a long time. Magnesium plays
important roles in all the major metabolisms: in oxidation-reduction and in
ionic regulation, among others. Zinc participates among others in the perception
of taste. An unbalanced copper metabolism homeostasis (due to dietary
deficiency) could be linked to Alzheimer disease. The iodine provided by the
thyroid hormone ensures the energy metabolism of the cerebral cells; the dietary
reduction of iodine during pregnancy induces severe cerebral dysfunction,
actually leading to cretinism. Among many mechanisms, manganese, copper, and
zinc participate in enzymatic mechanisms that protect against free radicals,
toxic derivatives of oxygen. More specifically, the full genetic potential of
the child for physical growth ad mental development may be compromised due to
deficiency (even subclinical) of micronutrients. Children and adolescents with
poor nutritional status are exposed to alterations of mental and behavioural
functions that can be corrected by dietary measures, but only to certain extend.
Indeed, nutrient composition and meal pattern can exert either immediate or
long-term effects, beneficial or adverse. Brain diseases during aging can also
be due to failure for protective mechanism, due to dietary deficiencies, for
instance in anti-oxidants and nutrients (trace elements, vitamins, non essential
micronutrients such as polyphenols) related with protection against free
radicals. Macronutrients are presented in the accompanying paper.
-----
Pediatrics. 2006 Oct 23; [Epub ahead of print]
Self-regulation of Slow Cortical Potentials: A New Treatment for
Children With Attention-Deficit/Hyperactivity Disorder.
Strehl U, Leins U, Goth G, Klinger C, Hinterberger T, Birbaumer N.
Institute of Medical Psychology and Behavioral Neurobiology.
OBJECTIVE: We investigated the effects of self-regulation of slow cortical
potentials for children with attention-deficit/hyperactivity disorder. Slow
cortical potentials are slow event-related direct-current shifts of the
electroencephalogram. Slow cortical potential shifts in the electrical negative
direction reflect the depolarization of large cortical cell assemblies, reducing
their excitation threshold. This training aims at regulation of cortical
excitation thresholds considered to be impaired in children with
attention-deficit/hyperactivity disorder. Electroencephalographic data from the
training and the 6-month follow-up are reported, as are changes in behavior and
cognition. METHOD: Twenty-three children with attention-deficit/hyperactivity
disorder aged between 8 and 13 years received 30 sessions of self-regulation
training of slow cortical potentials in 3 phases of 10 sessions each. Increasing
and decreasing slow cortical potentials at central brain regions was fed back
visually and auditorily. Transfer trials without feedback were intermixed with
feedback trials to allow generalization to everyday-life situations. In addition
to the neurofeedback sessions, children exercised during the third training
phase to apply the self-regulation strategy while doing their homework. RESULTS:
For the first time, electroencephalographic data during the course of slow
cortical potential neurofeedback are reported. Measurement before and after the
trials showed that children with attention-deficit/hyperactivity disorder learn
to regulate negative slow cortical potentials. After training, significant
improvement in behavior, attention, and IQ score was observed. The behavior
ratings included Diagnostic and Statistical Manual of Mental Disorders criteria,
number of problems, and social behavior at school and were conducted by parents
and teachers. The cognitive variables were assessed with the Wechsler
Intelligence Scale for Children and with a computerized test battery that
measures several components of attention. All changes proved to be stable at 6
months' follow-up after the end of training. Clinical outcome was predicted by
the ability to produce negative potential shifts in transfer sessions without
feedback. CONCLUSIONS: According to the guidelines of the efficacy of
treatments, the evidence of the efficacy of slow cortical potential feedback
found in this study reaches level 2: "possibly efficacious." In the absence of a
control group, no causal relationship between observed improvements and the
ability to regulate brain activity can be made. However, it could be shown for
the first time that good performance in self-regulation predicts clinical
outcome. "Good performance" was defined as the ability to produce negative
potential shifts in trials without feedback, because it is known that the
ability to self-regulate without feedback is impaired in children and adults
with attention problems. Additional research should focus on the control of
unspecific effects, medication, and subtypes to confirm the assumption that slow
cortical potential feedback is a viable treatment option for
attention-deficit/hyperactivity disorder. Regulation of slow cortical potentials
may involve similar neurobiological pathways as medical treatment. It is
suggested that regulation of frontocentral negative slow cortical potentials
affects the cholinergic-dopaminergic balance and allows children to adapt to
task requirements more flexibly.
-----
J Dev Behav Pediatr. 2006 Oct;27(5):410-6.
ADHD: New Pharmacological Treatments on the Horizon.
Lopez FA.
Children's Development Center, Winter Park, Florida.
ABSTRACT.: Attention-deficit/hyperactivity disorder (ADHD) is the most common
neurobehavioral disorder affecting school-age children. In many cases, symptoms
persist into adolescence and adulthood, causing significant lifelong impairments
in academic, career, and social functioning. The stimulants methylphenidate and
amphetamines have been used for decades as first-line therapy for the treatment
of ADHD. Short-acting stimulant formulations control symptoms only for a few
hours, creating the need for multiple daily doses of the medication. For
school-age children, this necessitates administering medication during school
hours, creating the potential for embarrassment and noncompliance. To offset
these problems, longer acting stimulant formulations have been developed.
Long-acting medications often control symptoms for up to 8 hours with only one
daily dose of the medication, eliminating the need for in-school administration.
Some long-acting stimulants are designed to control symptoms for up to 10 to 12
hours. Although stimulants are effective in most cases, some children are unable
to tolerate these medications. Nonstimulant options are available for the
treatment of ADHD and include atomoxetine, alpha-adrenergic agents, and
antidepressants. Of these, atomoxetine is the only medication approved to treat
ADHD. In spite of the number of medications available for the management of
ADHD, treatment options with greater flexibility and reduced side effects are
still desirable. A transdermal methylphenidate patch has recently been approved,
and advances to existing stimulants currently under development include an
amphetamine prodrug and a longer acting formulation of amphetamine. In addition,
a number of nonstimulant entities, including guanfacine and modafinil, are under
development for the treatment of ADHD.
-----
J Abnorm Child Psychol. 2006 Oct 7; [Epub ahead of print]
Consultation-based Academic Interventions for Children with ADHD:
Effects on Reading and Mathematics Achievement.
Dupaul GJ, Jitendra AK, Volpe RJ, Tresco KE, Lutz JG, Junod RE, Cleary KS,
Flammer LM, Mannella MC.
Department of Education and Human Services, Lehigh University, Bethlehem, 18015,
PA, USA, gjd3@lehigh.edu.
The purpose of this investigation was to evaluate the relative efficacy of two
consultation-based models for designing academic interventions to enhance the
educational functioning of children with attention-deficit/hyperactivity
disorder (ADHD). Children (N=167) meeting DSM-IV criteria for ADHD were randomly
assigned to one of two consultation groups: Individualized Academic Intervention
(IAI; interventions designed using a data-based decision-making model that
involved ongoing feedback to teachers) and Generic Academic Intervention (GAI;
interventions designed based on consultant-teacher collaboration, representing
"consultation as usual"). Teachers implemented academic interventions over 15
months. Academic outcomes (e.g., standardized achievement test, and teacher
ratings of academic skills) were assessed on four occasions (baseline, 3 months,
12 months, 15 months). Hierarchical linear modeling analyses indicated
significant positive growth for 8 of the 14 dependent variables; however,
trajectories did not differ significantly across consultation groups.
Interventions in the IAI group were delivered with significantly greater
integrity; however, groups did not differ with respect to teacher ratings of
treatment acceptability. The results of this study provide partial support for
the effectiveness of consultation-based academic interventions in enhancing
educational functioning in children with ADHD; however, the relative advantages
of an individualized model over "consultation as usual" have yet to be
established.
-----
J Am Acad Child Adolesc Psychiatry. 2006 Oct 4; [Epub ahead of print]
Safety and Tolerability of Methylphenidate in Preschool Children
With ADHD.
Wigal T, Greenhill L, Chuang S, McGough J, Vitiello B, Skrobala A, Swanson J,
Wigal S, Abikoff H, Kollins S, McCracken J, Riddle M, Posner K, Ghuman J, Davies
M, Thorp B, Stehli A.
Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of
California, Irvine; Dr. Abikoff is with the New York University Child Study
Center, New York; Drs. McCracken and McGough are with the University of
California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore;
Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill,
Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State
Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the
National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the
University of Arizona, Tucson.
OBJECTIVE:: To report on the safety and tolerability of methylphenidate (MPH) 3-
to 5-year-old children with attention-deficit/hyperactivity disorder (ADHD)
during 1 year of treatment. METHOD:: Exactly 183 children (3-5 years old)
entered a treatment study of MPH, consisting of a 1-week open-label lead-in (n =
183); a 5-week placebo-controlled, double-blind phase (n = 165); a 5-week
double-blind, parallel phase (n = 114); and 10 months of open-label maintenance
(n = 140 entered, 95 completed). Mean total daily MPH doses rose from the
titration trial best dose, 14.1 (+/-8.1) mg/day, to 20.5 (+/-9.7) mg/day mean
total daily dose at the end of maintenance. Pulse, blood pressure, and the
presence of treatment emergentadverse events (AEs), parent and teacher AE
ratings, and vital signs were recorded in each phase. RESULTS:: Thirty percent
of parents spontaneously reported moderate to severe AEs in all study phases
after baseline. These included emotional outbursts, difficulty falling asleep,
repetitive behaviors/thoughts, appetite decrease, and irritability. During
titration, decreased appetite (chi = 5.4, p <.03), trouble sleeping (chi = 5.4,
p <.03), and weight loss (chi = 4.0, p <.05) occurred statistically more often
on MPH than on placebo. During maintenance, trouble sleeping and appetite loss
persisted and other MPH-related AEs decreased. There were transient, one-time
pulse and blood pressure elevations in five children. Twenty-one children (11%)
discontinued because of drug-attributed AEs. CONCLUSIONS:: Eleven percent of
preschoolers discontinued treatment because of intolerable MPH AEs. Of the
serious AEs reported, one occurred in baseline, two in lead-in, three in
titration, one in parallel, and one in maintenance. Only one was possibly
related to MPH.
-----
CNS Spectr. 2006 Oct;11(10 Suppl 11):1-14.
Differential diagnosis and treatment of adult ADHD and
neighboring disorders.
Donnelly CL, Reimherr FW, Young JL.
Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
Attention-deficit/hyperactivity disorder (ADHD), once considered to be a
childhood disorder, is diagnosed in approximately 7 million adults in the United
States, as reported by The National Comorbidity Study. Although it is now
recognized that ADHD often persists into adulthood, the current diagnostic
criteria is geared toward symptom identification in children. Symptoms of
inattention, impulsivity, and hyperactivity evolve over the life cycle and
present differently in adults. Further complicating diagnosis is that ADHD is
associated with multiple functional impairments and comorbid psychiatric
disorders. The Multi-Modal Treatment Study of ADHD reported that only 32% of the
study population had ADHD alone; 29% had ADHD plus oppositional defiant disorder
and/or conduct disorder, 14% had ADHD plus anxiety or depression, and 25% had
all three disorders. Optimal treatment utilizes a multi-modal approach including
behavioral treatments combined with pharmacologic treatment strategies. Food and
Drug Administration-approved medications for ADHD include the stimulants and
nonstimulants, although tricyclic antidepressants and bupropion are also
commonly used. In this monograph, Craig L. Donnelly, MD, reviews the history of
ADHD and discusses the pathophysiologic progression of childhood symptoms into
those commonly exhibited by adults. Next, Frederick W. Reimherr, MD, reviews
comorbidity of ADHD and describes the Utah Criteria as a method of diagnosing
adults through recollection of childhood problems. Finally, Joel L. Young, MD,
reviews treatment approaches to adult ADHD and its comorbid conditions.
-----
J Clin Psychiatry. 2006 May;67(5):727-35.
A comparison of once-daily and divided doses of modafinil in
children with attention-deficit/hyperactivity disorder: a randomized,
double-blind, and placebo-controlled study.
Biederman J, Swanson JM, Wigal SB, Boellner SW, Earl CQ, Lopez FA; Modafinil
ADHD Study Group.
Department of Pediatric Psychopharmacology, Massachusetts General Hospital,
Boston 02114, USA. jbiederman@partners.org
OBJECTIVE: This randomized, double-blind, placebo-controlled study assessed the
efficacy and tolerability of several modafinil dosing regimens in children with
attention-deficit/hyperactivity disorder (ADHD) to determine whether modafinil
can be given once daily in pediatric ADHD. METHOD: Children and adolescents (age
range, 6-13 years) (N = 248) with DSM-IV-defined ADHD were enrolled in a 4-week,
double-blind, placebo-controlled study, conducted February-May 2002. The group
was assigned to receive oral (100-mg tablets) modafinil 300 mg once daily (300
mg in the morning followed by placebo at midday), modafinil 300 mg as a divided
dose (100/200 mg or 200/100 mg), or matching placebo. In children weighing > or
= 30 kg, a higher dose of 400 mg (200/200 mg) was evaluated. Efficacy measures
included the teacher-rated School Version and clinician-rated Home Version of
the ADHD Rating Scale-IV and the parent-completed Conners' ADHD/DSM-IV Scales.
RESULTS: 223 children completed the study. Those who received modafinil 300 mg
once daily showed a significantly greater improvement (change from baseline)
than those who received placebo in symptoms of ADHD across all rating scales and
subscales (all p < .05). Divided 300-mg doses of modafinil provided some
significant but inconsistent improvements in ADHD symptoms. In children weighing
> or = 30 kg, modafinil 400 mg (200/200 mg) was significantly superior to
placebo on clinician- and parent-completed scales (all p < .05). Insomnia was
the only adverse event to occur with significantly greater frequency in a
modafinil group (200/100) than in the placebo group (14% vs. 2%) (p = .03).
CONCLUSION: Modafinil significantly improved ADHD symptoms in children.
Once-daily dosing (300 mg) provided the most consistent improvement in symptoms.
All dosing regimens of modafinil were well tolerated.
-----
J Am Acad Child Adolesc Psychiatry. 2006 May;45(5):527-37.
Does prolonged therapy with a long-acting stimulant suppress
growth in children with ADHD?
Spencer TJ, Faraone SV, Biederman J, Lerner M, Cooper KM, Zimmerman B; Concerta
Study Group.
Massachusetts General Hospital, Boston, 02114, USA. spencer@helix.mgh.harvard.edu
OBJECTIVE: To investigate whether prolonged therapy with a long-acting stimulant
affects growth in children with attention-deficit/hyperactivity disorder (ADHD).
METHOD: One hundred seventy-eight children ages 6 to 13 years received OROS
methylphenidate (OROS MPH, CONCERTA) for at least 21 months. Height and weight
were measured monthly during the first year and every 3 months thereafter.
RESULTS: At baseline, subjects were approximately the expected height for their
age and somewhat heavier than expected. Subjects gained height steadily
throughout the study and were on average 0.23 cm less than expected at month 21.
Weight did not increase and BMI decreased slightly in the first 4 months.
Thereafter, weight Z score and BMI Z score remained relatively constant and
children were on average 1.23 kg less than expected at month 21. Previous
stimulant therapy tended to be associated with a smaller decrease in Z score
during the study compared with no previous stimulant therapy. Drug holidays did
not significantly affect growth. CONCLUSIONS: The effects of prolonged OROS MPH
therapy on growth were clinically insignificant and limited to slight decreases
in weight during the first months of therapy. Drug holidays did not reduce any
impact on growth and are thus of questionable utility for limiting potential
effects of treatment on growth.
-----
J Safety Res. 2006;37(2):167-73. Epub 2006 May 3.
How mothers parent their children with behavior disorders:
implications for unintentional injury risk.
Schwebel DC, Hodgens JB, Sterling S.
Department of Psychology, University of Alabama at Birmingham, 1300 University
Blvd, CH 415, 35294, USA. schwebel@uab.edu
INTRODUCTION: This study was designed to test the role of parental supervision
in explaining why children with behavior disorders have increased risk of
unintentional injury. METHOD: Children referred to a pediatric behavior
disorders clinic and their mothers were unknowingly observed in a "hazard room"
environment that housed several items that appeared dangerous but actually were
altered to be safe. RESULTS: Mother and child behavior in the hazard room was
correlated to parent-, teacher-, and observational-reports of children's
externalizing behavior patterns, children's injury history, and mother's
parenting styles. Maternal ignoring of children's dangerous behavior in the
hazard room was the strongest correlate to children's injury history.
CONCLUSIONS: Poor parental supervision might serve as a mechanism to explain why
children with behavior disorders, and those with oppositional behavior patterns
in particular, have increased risk of unintentional injury.
-----
J Music Ther. 2006 Spring;43(1):39-62.
Instructional and improvisational models of music therapy with
adolescents who have attention deficit hyperactivity disorder (ADHD): a
comparison of the effects on motor impulsivity.
Rickson DJ.
New Zealand School of Music, Massey University, Wellington. D.J.Rickson@massey.ac.nz
This study compared the impact of instructional and improvisational music
therapy approaches on the level of motor impulsivity displayed by adolescent
boys (n = 13) who have Attention Deficit Hyperactivity Disorder (ADHD). A
combination of a multiple contrasting treatment and an experimental control
group design was used. No statistical difference was found between the impact of
the contrasting approaches as measured by a Synchronised Tapping Task (STT)
(Humphrey, 2003) and the parent and teacher versions of Conners' Rating Scales (Conners,
1997) Restless-Impulsive (R-I) and Hyperactive-Impulsive (H-I) subscales.
However, while no firm conclusions can be drawn, there are indications that the
instructional approach may have contributed to a reduction of impulsive and
restless behaviors in the classroom. Further, over the period of the study, both
music therapy treatment groups significantly improved accuracy on the STT, and
teachers reported a significant reduction in Conners' DSM-IV Total and Global
Index subscale scores. These findings tentatively suggest that music therapy may
contribute to a reduction in a range of ADHD symptoms in the classroom, and that
increasing accuracy on the STT could be related to improvement in a range of
developmental areas-not specifically motor impulsivity.
-----
J Clin Psychiatry. 2006 Apr;67(4):611-9.
A randomized double-blind trial of paroxetine and/or
dextroamphetamine and problem-focused therapy for
attention-deficit/hyperactivity disorder in adults.
Weiss M, Hechtman L; The Adult ADHD Research Group.
Division of Child Psychiatry, Department of Psychiatry, University of British
Columbia, Vancouver, British Columbia, Canada. mweiss@cw.bc.ca
OBJECTIVE: To determine the effect of psychotherapy, dextroamphetamine, and/or
paroxetine on attention-deficit/hyperactivity-disorder (ADHD) in adults. METHOD:
Ninety-eight adults with DSM-IV ADHD were randomly assigned to receive
psychotherapy and dextroamphetamine, paroxetine, both, or placebo for 20 weeks.
A 2 x 2 factorial design compared patients who received dextroamphetamine versus
no dextroamphetamine with patients who received paroxetine versus no paroxetine.
Data were collected from August 2000 until May 2002. RESULTS: One half of the 98
enrolled subjects were found to have at least 1 lifetime mood or anxiety
disorder on the Structured Clinical Interview for DSM-IV. Sixty percent of
patients who received medication and 80% of those who received placebo completed
the 5-month trial. ADHD symptoms were significantly (p = .012) lower in patients
in the completer group who received dextroamphetamine. Paroxetine had no effect
on ADHD. Hamilton Rating Scales for Anxiety (HAM-A) and Depression (HAM-D)
scores were low to start, and no treatment differences were evident at endpoint.
Significantly (p < .001) more patients in the completer group were rated by
clinicians as ADHD responders if they received dextroamphetamine (85.7%) or
combined treatment (66.7%) versus paroxetine (20.0%) or placebo (21.1%).
Significantly (p = .003) more patients in the completer group were rated by
clinicians as mood/anxiety responders if they received paroxetine (100%) or
combined treatment (73.3%) versus those receiving dextroamphetamine (57.15%) or
placebo (47.4%). Clinicians rated any patient who received medication and
psychological therapy as significantly more improved overall than those who
received placebo and psychological therapy (intent to treat: p = .033;
completers: p = .001). CONCLUSION: ADHD symptoms improved with dextroamphetamine.
Mood and internalizing symptoms were seen as improved with paroxetine by
clinicians, despite absence of response on the HAM-A and HAM-D. The presence of
a lifetime internalizing disorder attenuated the response to dextroamphetamine.
Patients who received both dextroamphetamine and paroxetine had more severe
adverse events but did not show greater improvement overall than patients
treated with 1 medication. Clinical Trials Registry #GSK707.
-----
J Clin Psychiatry. 2006 Apr;67(4):554-66.
A systematic review of modafinil: Potential clinical uses and
mechanisms of action.
Ballon JS, Feifel D.
Department of Psychiatry, University of California, San Diego, CA, USA.
BACKGROUND: Modafinil is a novel wake-promoting agent that has U.S. Food and
Drug Administration approval for narcolepsy and shift work sleep disorder and as
adjunctive treatment of obstructive sleep apnea/hypopnea syndrome. Modafinil has
a novel mechanism and is theorized to work in a localized manner, utilizing
hypocretin, histamine, epinephrine, gamma-aminobutyric acid, and glutamate. It
is a well-tolerated medication with low propensity for abuse and is frequently
used for off-label indications. The objective of this study was to
systematically review the available evidence supporting the clinical use of
modafinil. DATA SOURCES: The search term modafinil OR Provigil was searched on
PubMed. Selected articles were mined for further potential sources of data.
Abstracts from major scientific conferences were reviewed. Lastly, the
manufacturer of modafinil in the United States was asked to provide all
publications, abstracts, and unpublished data regarding studies of modafinil.
DATA SYNTHESIS: There have been 33 double-blind, placebo-controlled trials of
modafinil. Additionally, numerous smaller studies have been performed, and case
reports of modafinil's use abound in the literature. CONCLUSIONS: Modafinil is a
promising drug with a large potential for many uses in psychiatry and general
medicine. Treating daytime sleepiness is complex, and determining the precise
nature of the sleep disorder is vital. Modafinil may be an effective agent in
many sleep conditions. To date, the strongest evidence among off-label uses
exists for the use of modafinil in attention-deficit disorder, postanesthetic
sedation, and cocaine dependence and withdrawal and as an adjunct to
antidepressants for depression.
-----
Expert Rev Neurother. 2006 Apr;6(4):551-61.
Long-term outcomes of stimulant medication in attention-deficit
hyperactivity disorder.
Poulton A.
Western Clinical School, Nepean Campus, University of Sydney, Australia.
sallypoulton@westnet.com.au
The rate of prescribing of stimulant medication for the treatment of
attention-deficit hyperactivity disorder (ADHD) has been progressively
increasing in countries such as the USA and Australia. In the short term,
stimulant medication is effective in reducing the symptoms of ADHD and appears
well tolerated with relatively minor side effects. In the long term, much of the
benefit of stimulant medication disappears after medication is ceased. Studies
have demonstrated only marginal improvements in adult outcomes following a
period of treatment in childhood. This may be owing to the beneficial effects
being masked by the variability of the condition, the developmental changes in
symptomatology that happen with maturation and the substantial influence of
social and environmental factors. Stimulant medication may give some protection
against later substance abuse. Stimulant medication may slightly elevate the
blood pressure and possibly increase susceptibility to seizures and to tics and
Tourette syndrome. Starting treatment with stimulant medication is usually
associated with weight loss and a transient slowing of the height velocity,
although it is believed that most children catch up during puberty. No studies
were found that listed strokes or heart attacks as potential or actual
complications, although one individual from a group of normal controls died
suddenly of cardiac arrest in adolescence. It would appear that the medical
complications associated with amphetamine addiction are not relevant to the
therapeutic use of stimulant medication in the treatment of ADHD, although there
is limited information on extended periods of treatment lasting 10 years or
more.
-----
Expert Rev Neurother. 2006 Apr;6(4):455-68.
A review of the use of modafinil for attention-deficit
hyperactivity disorder.
Turner D.
University of Cambridge, Department of Psychiatry, Box 189, Addenbrooke's
Hospital, Cambridge, CB2 2QQ UK. dct23@cam.ac.uk
Modafinil (Provigil) is a novel wakefulness-promoting agent that has been shown
to have greater efficacy than placebo in the treatment of attention-deficit
hyperactivity disorder (ADHD) in children and adults. In particular, three
large, drug-company sponsored trials of a film-coated formulation of modafinil (modafinil-ADHD;
Sparlon) in children and adolescents with ADHD demonstrated consistent
improvements in ADHD symptoms compared with placebo. Mean reductions in symptom
ratings (measured using the ADHD-Rating Scale-IV school version questionnaire)
ranged from 15.0 to 19.7 (7.3 to 10.1 for placebo). The most common adverse
events were insomnia, headache and decreased appetite. Modafinil was generally
well tolerated with most side effects considered mild to moderate in severity.
Modafinil may have advantages over current therapies for ADHD in that it can be
administered once daily and has fewer reinforcing properties than traditional
stimulants. Modafinil could potentially be a valuable new treatment option for
patients with ADHD. However, rigorous comparative studies with current
first-line treatments for ADHD and longer-term independent studies are necessary
before modafinil's role in the treatment of ADHD can be fully established.
-----
Curr Opin Pediatr. 2006 Apr;18(2):189-195.
Attention deficit/hyperactivity disorder: complexities and
controversies.
Schonwald A, Lechner E.
aChildren's Hospital, Boston, Massachusetts, USA bUniversity of Vermont College
of Medicine, Burlington, Vermont, USA.
PURPOSE OF REVIEW: Attention deficit/hyperactivity disorder continues to be a
prevalent childhood behavioral disorder, with significant clinical and media
interest. Providers must be current with research findings that impact the
evolving understanding of this complex entity. This article summarizes recent
progress in our view of attention deficit/hyperactivity disorder, with emphasis
on controversies around diagnosis and treatment, and future management
directions. RECENT FINDINGS: Literature about attention deficit/hyperactivity
disorder in 2005 further enhanced our understanding of the genetic contribution
to the expression of attention deficit/hyperactivity disorder, with exploration
of sophisticated genetic models and their dynamic interaction with exposures and
experiences. Previous literature focuses on conventional treatment; new
developments in pharmacological/alternative options add to treatment choices,
but have brought well publicized controversies. Furthermore, optimal management
continues to gain evidence-based support. SUMMARY: Attention
deficit/hyperactivity disorder is a subject of great interest to families,
providers, researchers, and public forums. Scientific investigation supports a
primary genetic contribution, but the relationship of molecular bases and
environmental exposures appears intricate and complex. With increased awareness
of this disorder, diagnostic dilemmas and medication side effects are more
widely understood, topics particularly important to clinicians. Stimulant
treatment remains the mainstay of intervention, but new delivery forms and
nonstimulant options are potential therapies as well.
-----
J Am Acad Child Adolesc Psychiatry. 2006 Mar 10; [Epub ahead of print]
A Randomized, Double-Blind, Placebo-Controlled Study of Modafinil
Film-Coated Tablets in Children and Adolescents With
Attention-Deficit/Hyperactivity Disorder.
Greenhill LL, Biederman J, Boellner SW, Rugino TA, Sangal RB, Earl CQ, Jiang JG,
Swanson JM.
Dr. Greenhill is with the New York State Psychiatric Institute, New York; Dr.
Biederman is with the Department of Pediatric Psychopharmacology, Massachusetts
General Hospital, Boston; Dr. Boellner is with the Neurology and Clinical Study
Center, Little Rock, AR; Dr. Rugino is with Children's Specialized Hospital,
Mountainside, NJ; Dr. Sangal is with Clinical Neurophysiology Services, PC,
Troy, MI; Drs. Earl and Jiang are with Cephalon, Inc., West Chester, PA; and Dr.
Swanson is with the University of California at Irvine Child Development Center.
OBJECTIVE:: To evaluate the efficacy and tolerability of modafinil in children
and adolescents, ages 7 to 17, with attention-deficit/hyperactivity disorder
(ADHD). METHOD:: In this 9-week, double-blind, flexible-dose study, patients
were randomized to once-daily modafinil (170-425 mg) or placebo. Assessments
included ADHD Rating Scale-IV (ADHD-RS-IV) School and Home Versions and Clinical
Global Impression of Improvement (CGI-I) scale. RESULTS:: Two hundred patients
were randomized. Modafinil produced significant reductions in ADHD-RS-IV total
scores at school (n = 128; mean change +/- SD: -17.5 +/- 13.1 points) compared
with placebo (n = 66; -9.7 +/- 10.3 points; p < .0001). Similarly, modafinil
reduced ADHD-RS-IV total scores at home compared with placebo (-17.6 +/- 13.3
versus -7.5 +/- 11.8 points; p < .0001). Fifty-two percent of patients
randomized to modafinil and 18% of those randomized to placebo met prestudy
criteria for responder on the CGI-I (p < .0001). Randomization to modafinil was
associated with significantly more insomnia, headache, decreased appetite, and
weight loss than randomization to placebo, but discontinuation attributed to
adverse events did not differ statistically between treatment groups (modafinil,
5%; placebo, 6%). CONCLUSION:: Modafinil was well tolerated and reduced ADHD
symptoms at school and home compared with placebo.
-----
J Am Acad Child Adolesc Psychiatry. 2006 Mar 10; [Epub ahead of print]
Sleep Hygiene and Melatonin Treatment for Children and
Adolescents With ADHD and Initial Insomnia.
Weiss M, Wasdell M, Bomben M, Rea K, Freeman R.
Dr. Weiss, Mr. Wasdell, and Ms. Bomben are with the Division of Child
Psychiatry, University of British Columbia; Ms. Rea is with the Provincial ADHD
Program, Children's and Women's Health Centre of British Columbia; and Dr.
Freeman is with the British Columbia Children's Hospital and the Departments of
Psychiatry and Pediatrics, University of British Columbia, Vancouver, British
Columbia, Canada.
OBJECTIVE:: To evaluate the efficacy of sleep hygiene and melatonin treatment
for initial insomnia in children with attention-deficit/hyperactivity disorder
(ADHD). METHOD:: Twenty-seven stimulant-treated children (6-14 years of age)
with ADHD and initial insomnia (>60 minutes) received sleep hygiene
intervention. Nonresponders were randomized to a 30-day double-blind,
placebo-controlled, crossover trial of 5-mg pharmaceutical-grade melatonin
provided by the study's sponsor. RESULTS:: Sleep hygiene reduced initial
insomnia to <60 minutes in 5 cases, with an overall effect size in the group as
a whole of 0.67. Analysis of the trial data able to be evaluated showed a
significant reduction in initial insomnia of 16 minutes with melatonin relative
to placebo, with an effect size of 0.6. Adverse events were generally mild and
not different from those recorded with placebo treatment. The effect size of the
combined sleep hygiene and melatonin intervention from baseline to 90 days'
posttrial was 1.7, with a mean decrease in initial insomnia of 60 minutes.
Improved sleep had no demonstrable effect on ADHD symptoms. CONCLUSION::
Combined sleep hygiene and melatonin was a safe and effective treatment for
initial insomnia in children with ADHD taking stimulant medication.
-----
J Dev Behav Pediatr. 2006 Feb;27(1):1-10.
Long-term stimulant medication treatment of
attention-deficit/hyperactivity disorder: results from a population-based study.
Barbaresi WJ, Katusic SK, Colligan RC, Weaver AL, Leibson CL, Jacobsen SJ.
Department of Pediatric and Adolescent Medicine, Division of Developmental and
Behavioral Pediatrics, Mayo Clinic College of Medicine, Rochester, MN 55905,
USA. barbaresi.william@mayo.edu
The purpose of this study was to offer detailed information about stimulant
medication treatment provided throughout childhood to 379 children with
research-identified attention-deficit hyperactivity disorder (ADHD) in the
1976-1982 Rochester, MN, birth cohort. Subjects were retrospectively followed
from birth until a mean of 17.2 years of age. The complete medical record of
each subject was reviewed. The history and results of each episode of stimulant
treatment were compared by gender, DSM-IV subtype of ADHD, and type of stimulant
medication. Overall, 77.8% of subjects were treated with stimulants. Boys were
1.8 times more likely than girls to be treated. The median age at initiation
(9.8 years), median duration of treatment (33.8 months), and likelihood of
developing at least one side effect (22.3%) were not significantly different by
gender. Overall, 73.1% of episodes of stimulant treatment were associated with a
favorable response. The likelihood of a favorable response was comparable for
boys and girls. Treatment was initiated earlier for children with either ADHD
combined type or ADHD hyperactive-impulsive type than for children with ADHD
predominantly inattentive type and duration of treatment was longer for ADHD
combined type. There was no association between DSM-IV subtype and likelihood of
a favorable response or of side effects. Dextroamphetamine and methylphenidate
were equally likely to be associated with a favorable response, but
dextroamphetamine was more likely to be associated with side effects. These
results demonstrate that the effectiveness of stimulant medication treatment of
ADHD provided throughout childhood is comparable to the efficacy of stimulant
treatment demonstrated in clinical trials.
-----
Rev Neurol. 2006 Feb 13;42 Suppl 2:S25-7.
[Attention deficit hyperactivity disorder and mental
retardation.]
[Article in Spanish]
Fernandez-Jaen A.
Hospital Universitario La Paz, 28046 Madrid, Espana.
INTRODUCTION. Attention deficit hyperactivity disorder (ADHD) is a common
condition in children with mental retardation (MR), with a prevalence rate of
between 4 and 15%. It is therefore necessary to examine the epidemiological
characteristics of neurodevelopmental disorders in patients with MR, evaluate
diagnostic protocols and especially update the pharmacological treatment of ADHD
in children with MR. DEVELOPMENT. The study of ADHD in patients with mild mental
retardation is no different to that carried out in children without MR. No
neuropsychological instruments are available to measure the executive functions
properly in patients with severe mental retardation. Neuroleptic and
psychostimulant agents are the two groups of drugs that are most commonly used
to treat behavioural problems in children with MR. Methylphenidate is effective
in three quarters of the children with MR at preschool ages. It has proved to be
effective in the clinical profiles and in psychometric studies. Other forms of
treatment, such as clonidine or fenfluramine, have also proved to be effective
to a certain extent in patients with MR, especially in the clinical setting.
CONCLUSIONS. ADHD is more frequent in patients with MR than in the general
population. The diagnostic methodology is usually the same as that used in
patients without MR. Stimulation treatment is the most specifically indicated
for the treatment of attentional and behavioural problems in these children.
-----
Rev Neurol. 2006 Feb 13;42 Suppl 2:S37-51.
[Attention deficit hyperactivity disorder and sleep disorders.]
[Article in Spanish]
Betancourt-Fursow de Jimenez YM, Jimenez-Leon JC, Jimenez-Betancourt CS.
Instituto Docente de Urologia, Valencia, Venezuela.
INTRODUCTION. The purpose of the present review was to analyse the comorbidity
that exists between attention deficit hyperactivity disorder (ADHD) and sleep
disorders in children and adolescents, together with their clinical
characteristics, diagnosis and treatment regimens. DEVELOPMENT. ADHD and sleep
disorders are a frequent cause of visits in neuropaediatric departments. Around
25% of children with ADHD have some kind of sleep disorder but, unlike the case
of adults, these often remain undetected. We nearly always choose to improve
hyperactivity, attention deficit and impulsiveness symptomatically and forget to
treat the associated sleep disorder. CONCLUSIONS. There is a clear correlation
between ADHD and sleep disorders and they are very common in visits to the
neuropaediatric department. Diagnosis of these patients is clinical.
Neurophysiological evaluation, especially using polysomnography, provides
objective confirmation of the symptoms. Novel treatments such as melatonin and
other drugs are now available to improve the sleep pattern. By improving these
children's sleep, the symptoms of ADHD are diminished and thus avoid the need to
administer psychostimulants, which have undesirable side effects that produce a
great deal of anxiety in the parents of these children.
-----
Biol Psychiatry. 2006 Feb 21; [Epub ahead of print]
ABT-089, A Neuronal Nicotinic Receptor Partial Agonist, for the
Treatment of Attention-Deficit/Hyperactivity Disorder in Adults: Results of a
Pilot Study.
Wilens TE, Verlinden MH, Adler LA, Wozniak PJ, West SA.
Department of Psychiatry (TEW), Massachusetts General Hospital, Boston,
Massachusetts.
BACKGROUND: This pilot study was designed to evaluate ABT-089, a neuronal
nicotinic receptor partial agonist, as treatment for adult
attention-deficit/hyperactivity disorder (ADHD). METHODS: Adults with ADHD
received placebo, 2 mg, 4 mg, or 20 mg of ABT-089 for 2 weeks each in a
randomized, double-blind, placebo-controlled, 4 x 4 Latin square design for a
total of 8 weeks. In addition to the primary outcome, the Conner's Adult ADHD
Rating Scale (CAARS), secondary rating scales, and neuropsychological and safety
assessments were completed. RESULTS: A total of 11 adults with
well-characterized ADHD completed this crossover study. ABT-089 b.i.d. was
superior to placebo for the CAARS Total Symptom Score, which was the primary
endpoint (placebo: 38.0 +/- 1.9; 2 mg b.i.d.: 32.2 +/- 1.9, one-tail p = .021; 4
mg b.i.d.: 33.2 +/- 1.9, p = .047; 20 mg b.i.d.: 33.5 +/- 1.9, p = .056).
ABT-089 was also superior to placebo for the CAARS ADHD Index and
Hyperactive/Impulsive scores and the Clinical Global Impression-ADHD Severity
score. On the clinical efficacy endpoints, CAARS Total Symptom Score and CAARS
Hyperactive/Impulsive score, a shallow inverted U-shaped dose-response curve was
observed; however, the dose-response curve for attention and memory effects as
measured by computerized cognitive testing seemed dose-linear. No clinically
meaningful findings in safety assessments or side effect profile were observed.
CONCLUSIONS: Data from this pilot study suggest that ABT-089 might be effective
in treating adult ADHD and that it is well tolerated. On the basis of these
promising results, larger, parallel-group ABT-089 studies of longer duration are
warranted.
-----
Arch Pediatr Adolesc Med. 2006 Jan;160(1):82-90.
Multisite controlled study of OROS methylphenidate in the
treatment of adolescents with attention-deficit/hyperactivity disorder.
Wilens TE, McBurnett K, Bukstein O, McGough J, Greenhill L, Lerner M, Stein MA,
Conners CK, Duby J, Newcorn J, Bailey CE, Kratochvil CJ, Coury D, Casat C,
Denisco MJ, Halstead P, Bloom L, Zimmerman BA, Gu J, Cooper KM, Lynch JM.
Pediatric Psychopharmacology Unit, Massachusetts General Hospital, YAW-6-6A, 32
Fruit Street, Boston, MA 02114, USA. twilens@partners.org
BACKGROUND: Despite the persistence of attention-deficit/hyperactivity disorder
(ADHD) into adolescence, little is known about the efficacy and tolerability of
stimulant medications in this age group. OBJECTIVE: To report the results of a
multisite controlled study among adolescents with ADHD evaluating the efficacy
and tolerability of osmotic-release oral system (OROS) methylphenidate. DESIGN:
Adolescents (N = 220) having a confirmed Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition diagnosis of ADHD underwent dose titration to
identify dosages of OROS methylphenidate that improved symptoms to predefined
criteria. Subjects successfully completing the dose titration phase (n = 177) (ie,
tolerated and responded to treatment and adhered to the protocol) were
randomized to receive 2 weeks' treatment with their individualized dosage of
OROS methylphenidate (18, 36, 54, or 72 mg once daily) or placebo. Treatment
effectiveness was measured using investigator, parent, and adolescent
assessments of ADHD. RESULTS: A significant reduction from baseline in the
investigator-rated ADHD Rating Scale, the primary efficacy measure, was found
with OROS methylphenidate treatment compared with placebo. Similar findings were
noted with parent- and adolescent-report measures. Based on a Clinical Global
Impression improvement subscale score of much or very much improved, 52% of
subjects in the OROS methylphenidate group improved compared with 31% receiving
placebo. Thirty-seven percent of subjects required the maximum dosage of 72
mg/d. The incidence of drug-related adverse events was similar between the 2
study groups. CONCLUSION: In adolescents, once-daily OROS methylphenidate
significantly reduced ADHD symptoms and was well tolerated using dosages up to
72 mg/d.
-----
J Paediatr Child Health. 2005 Dec;41(12):625-30.
Management of attention deficit hyperactivity disorder: a
parental perspective.
Concannon PE, Tang YP.
Child and Family Health Service, Royal North Shore and Ryde Health Sector,
Sydney, New South Wales, Australia. pconcann@nsccahs.health.nsw.gov.au
OBJECTIVES: There are few studies exploring parental perceptions of the
diagnosis and overall treatment of their children with attention deficit
hyperactivity disorder (ADHD). This community-based study was conducted to
consider this important aspect of care. METHODS: A total of 7 226 (65%) parents
responded to a community survey of 11 184 children aged 10-12 years living in
northern Sydney in 2000, out of which 278 children with ADHD were identified.
Their parents completed an anonymous questionnaire covering their perceptions
relating to diagnosis, treatment and overall management. RESULTS: Only 66% of
parents recalled the use of questionnaires or rating scales. There were 82% of
children who had trialed medication and 66% of these were still taking it.
Behavioural intervention had occurred in 42% of the children. Non-conventional
treatments, most commonly elimination diet and/or fatty acid supplementation,
had been used in 71% of the children. These were considered helpful in one-third
of cases. A total of 55% of parents reported being either satisfied or very
satisfied with their child's care. Parents were more likely to report
satisfaction when their children were on medication and when reviews were held
at least 6 monthly. Lack of educational support and teachers' understanding of
ADHD were identified as ongoing issues. CONCLUSION: Parental responses suggested
that adherence to recommended diagnostic guidelines was inadequate. Behavioural
intervention was underutilized despite its documented positive role.
Non-conventional therapies were widely used and considered helpful in one-third
of the children who used them. Use of stimulant medication and frequent reviews
were more likely to be associated with overall management satisfaction.
-----
Appl Psychophysiol Biofeedback. 2005 Dec;30(4):365-73.
Neurofeedback: an alternative and efficacious treatment for
attention deficit hyperactivity disorder.
Fox DJ, Tharp DF, Fox LC.
Advanced Neurotherapy Solutions, College Station, Texas.
Current research has shown that neurofeedback, or EEG biofeedback as it is
sometimes called, is a viable alternative treatment for Attention Deficit
Hyperactivity Disorder (ADHD). The aim of this article is to illustrate current
treatment modalities(s), compare them to neurofeedback, and present the benefits
of utilizing this method of treatment to control and potentially alleviate the
symptoms of ADHD. In addition, this article examines the prevalence rates and
possible etiology of ADHD, the factors associated with ADHD and brain
dysfunction, the current pharmacological treatments of ADHD, Ritalin, and the
potential risks and side effects. Behavior modification and cognitive behavioral
treatment for ADHD is discussed as well. Lastly, a brief history of the study of
neurofeedback, treatment successes and clinical benefits, comparisons to
medication, and limitations are presented.
-----
Indian J Med Sci. 2005 Dec;59(12):546-55.
Attention deficit hyperactivity disorder: A review for family
physicians.
Karande S.
Learning Disability Clinic, Division of Pediatric Neurology, Department of
Pediatrics, Lokmanya Tilak Municipal Medical College and General Hospital, Sion,
Mumbai, India. karandesunil@yahoo.com.
Attention deficit hyperactivity disorder (ADHD) is a chronic behavioral disorder
characterized by persistent hyperactivity, impulsivity, and inattention that
impairs educational achievement and/or social functioning. Its diagnosis is made
by ascertaining whether the child's specific behaviors meet the diagnostic and
statistical manual of mental disorders-IV-revised criteria. Its etiology is
still unclear but recent studies suggest that genetics plays a major role in
conferring susceptibility. Comorbidity with psychiatric disorders such as
anxiety disorder, depression, oppositional defiant disorder and conduct
disorder; and with specific learning disability is not uncommon. Although
medication works well in most cases of ADHD, optimal treatment requires
integrated medical and behavioral treatment. Methylphenidate (MPH) and
atomoxetine are the two drugs being currently prescribed and their efficacy in
decreasing the symptoms of ADHD is well documented. Pyschoeducational
interventions in school can help increase the successful functioning of affected
children and improve their academic performance. Almost half of affected
children continue to show significant symptoms of the disorder into adolescence
and young adulthood. The family physician can play an important role in
detecting this condition early, coordinating its assessment and treatment,
counseling the parents and classroom teacher, and monitoring the child's
academic and psychosocial progress on a long-term basis.
-----
Neurology. 2005 Dec 27;65(12):1941-9.
Atomoxetine treatment in children and adolescents with ADHD and
comorbid tic disorders.
Allen AJ, Kurlan RM, Gilbert DL, Coffey BJ, Linder SL, Lewis DW, Winner PK, Dunn
DW, Dure LS, Sallee FR, Milton DR, Mintz MI, Ricardi RK, Erenberg G, Layton LL,
Feldman PD, Kelsey DK, Spencer TJ.
Lilly Research Laboratories, Indianapolis, IN 46285, USA. allenaj@lilly.com
OBJECTIVE: To test the hypothesis that atomoxetine does not significantly worsen
tic severity relative to placebo in children and adolescents with attention
deficit/hyperactivity disorder (ADHD) and comorbid tic disorders. METHODS: Study
subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental
Disorders-IV criteria for ADHD, and had concurrent Tourette syndrome or chronic
motor tic disorder. Patients were randomly assigned to double-blind treatment
with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18
weeks. RESULTS: Atomoxetine treatment was associated with greater reduction of
tic severity at endpoint relative to placebo, approaching significance on the
Yale Global Tic Severity Scale total score (-5.5 +/- 6.9 vs -3.0 +/- 8.7, p =
0.063) and Tic Symptom Self-Report total score (-4.7 +/- 6.5 vs -2.9 +/- 5.2, p
= 0.095) and achieving significance on the Clinical Global Impressions (CGI)
tic/neurologic severity scale score (-0.7 +/- 1.2 vs -0.1 +/- 1.0, p = 0.002).
Atomoxetine patients also showed greater improvement on the ADHD Rating Scale
total score (-10.9 +/- 10.9 vs -4.9 +/- 10.3, p < 0.001) and CGI severity of
ADHD/psychiatric symptoms scale score (-0.8 +/- 1.1 vs -0.3 +/- 1.0, p = 0.015).
Discontinuation rates were not significantly different between treatment groups.
Atomoxetine patients had greater increases in heart rate and decreases of body
weight, and rates of treatment-emergent decreased appetite and nausea were
higher. No other clinically relevant treatment differences were seen in any
other vital sign, adverse event, or electrocardiographic or laboratory measures.
CONCLUSIONS: Atomoxetine did not exacerbate tic symptoms. Rather, there was some
evidence of reduction in tic severity with a significant reduction of attention
deficit/hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and
well tolerated.
-----
J Child Adolesc Psychopharmacol. 2005 Dec;15(6):947-55.
An open trial of adjunctive donepezil in
attention-deficit/hyperactivity disorder.
Wilens TE, Waxmonsky J, Scott M, Swezey A, Kwon A, Spencer TJ, Biederman J.
Pediatric Psychopharmacology Unit, YAW 6A, Massachusetts General Hospital and
Harvard Medical School, Boston, Massachusetts.
Objective: Despite available pharmacotherapeutics, a number of youths with
attentiondeficit/ hyperactivity disorder (ADHD) continue to experience residual
symptoms and prominent executive function (EF) deficits resulting in impairment
in multiple domains. We sought to determine if donepezil, used adjunctively to
stimulant medication, would improve residual symptoms of ADHD and EF deficits.
Methods: In a 12-week open trial, we treated 7 children and 6 adults who had
ADHD and evidence of further EF deficits with adjunctive donepezil. All subjects
were stabilized on stimulants, at which time donepezil was initiated at 2.5 mg
daily and increased to a maximum of 10 mg over the 12-week trial. Results: Of 13
subjects receiving medication, 7 completed the trial. There was no clinically or
statistically significant improvement in the ADHD Rating Scale and the Executive
Function Checklist, our primary outcome measures. A majority of individuals
experienced nonserious adverse events. Conclusions: Results of this small open
study suggest that donepezil augmentation of stimulants is not well tolerated
and does not appear useful for the treatment of residual ADHD and/or EF
deficits.
-----
Biol Psychiatry. 2005 Dec 19; [Epub ahead of print]
A Randomized, Placebo-Controlled Trial of OROS Methylphenidate in
Adults with Attention-Deficit/Hyperactivity Disorder.
Biederman J, Mick E, Surman C, Doyle R, Hammerness P, Harpold T, Dunkel S,
Dougherty M, Aleardi M, Spencer T.
Clinical and Research Program in Pediatric Psychopharmacology at the
Massachusetts General Hospital (JB, EM, CS, RD, PH, TH, TS); Department of
Psychiatry at Harvard Medical School (JB, EM, CS, RD, PH, TH, SD, MD, MA, TS),
Boston, Massachusetts.
BACKGROUND: The objective of this study was to evaluate the safety and efficacy
of once-daily OROS methylphenidate (MPH) in the treatment of adults with DSM-IV
attention-deficit/hyperactivity disorder (ADHD). METHODS: We conducted a
randomized, 6-week, placebo-controlled, parallel-design study of OROS MPH in 141
adult subjects with DSM-IV ADHD, using standardized instruments for diagnosis.
OROS MPH or placebo was initiated at 36 mg/day and titrated to optimal response,
depending on efficacy and tolerability, up to 1.3 mg/kg/day. RESULTS: Treatment
with OROS MPH was associated with clinically and statistically significant
reductions in DSM-IV symptoms of inattention and hyperactivity/impulsivity
relative to subjects treated with placebo. At endpoint, 66% of subjects (n = 44)
receiving OROS MPH and 39% of subjects (n = 23) receiving placebo attained our a
priori definition of response of much or very much improved on the Clinical
Global Impression-Improvement scale plus a >30% reduction in Adult ADHD
Investigator System Report Scale score. OROS MPH was associated with small but
statistically significant increases in systolic blood pressure (3.5 +/- 11.8 mm
Hg), diastolic blood pressure (4.0 +/- 8.5 mm Hg), and heart rate (4.5 +/- 10.5
bpm). CONCLUSIONS: These results show that treatment with OROS MPH in daily
doses of up to 1.3 mg/kg/day was effective in the treatment of adults with ADHD.
Because of the potential for increases in blood pressure and heart rate,
subjects receiving treatment with MPH should be monitored for changes in blood
pressure parameters during treatment.
-----
Indian J Pediatr. 2005 Nov;72(11):961-7.
Poor school performance.
Karande S, Kulkarni M.
Learning Disability Clinic, Division of Pediatric Neurology, Department of
Pediatrics, Lokmanya Tilak Municipal Medical College and General Hospital, Sion,
Mumbai, India. karandesunil@yahoo.com
Education is one of the most important aspects of human resource development.
Poor school performance not only results in the child having a low self-esteem,
but also causes significant stress to the parents. There are many reasons for
children to under perform at school, such as, medical problems, below average
intelligence, specific learning disability, attention deficit hyperactivity
disorder, emotional problems, poor socio-cultural home environment, psychiatric
disorders and even environmental causes. The information provided by the
parents, classroom teacher and school counselor about the child's academic
difficulties guides the pediatrician to form an initial diagnosis. However, a
multidisciplinary evaluation by an ophthalmologist, otolaryngologist, counselor,
clinical psychologist, special educator, and child psychiatrist is usually
necessary before making the final diagnosis. It is important to find the
reason(s) for a child's poor school performance and come up with a treatment
plan early so that the child can perform up to full potential.
-----
Indian J Pediatr. 2005 Nov;72(11):953-60.
Pharmacologic treatment of attention-deficit hyperactivity
disorder.
Greydanus DE.
Pediatrics and Human Development, Kalamazoo Center for Medical Studies,
Kalamazoo, Michigan, USA. Greydanus@kcms.msu.edu
Attention-deficit hyperactivity disorder (ADHD) is highly prevalent in children
and adolescents. Highly effective pharmacological treatments are available that
allow the child and the adolescent to function at his/her full potential.
Various preparations of methylphenidate and amphetamines have been used for a
long time in the treatment of ADHD. This article reviews these and some of the
newer drugs used in the treatment of ADHD, including atomoxetine and bupropion.
-----
MMWR Morb Mortal Wkly Rep. 2005 Sep 2;54(34):842-7.
Mental health in the United States. Prevalence of diagnosis and
medication treatment for attention-deficit/hyperactivity disorder—United States,
2003.
Centers for Disease Control and Prevention (CDC).
Attention-deficit/hyperactivity disorder (ADHD), previously known as attention
deficit disorder, is a neurobehavioral disorder characterized by pervasive
inattention and hyperactivity-impulsivity that often results in substantial
functional impairment. Prevalence estimates of ADHD in school-aged children have
ranged from 2% to 18% in community samples. Although stimulant medications are
an effective first-line treatment for ADHD , concern persists regarding the
possible side effects and long-term health outcomes associated with stimulant
consumption. Estimating the number of children who have had ADHD diagnosed and
are currently taking medication for the disorder is an important step toward
understanding the overall burden of ADHD in the United States. Previously,
population-based estimates of medication treatment for ADHD were not available
or were limited by their lack of generalizability. To estimate rates of
parent-reported ADHD diagnosis and medication treatment for ADHD, CDC analyzed
data from the 2003 National Survey of Children's Health (NSCH). This report
describes the results of that analysis, which indicated that, in 2003,
approximately 4.4 million children aged 4-17 years were reported to have a
history of ADHD diagnosis; of these, 2.5 million (56%) were reported to be
taking medication for the disorder. Because both substantial health risks and
benefits might be associated with medication treatment for ADHD, further study
of this population of children with ADHD is needed.
-----
Harefuah. 2005 Aug;144(8):572-6, 597.
[Attention deficit hyperactivity disorder: pharmacological
options that are not "Ritalin"]
[Article in Hebrew]
Shmueli D, Gross-Tsur V.
Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem, Israel.
doritshmueli66@hotmail.com
Methylphenidate (Ritalin) is the drug of choice for the treatment of Attention
Deficit Hyperactivity Disorder (ADHD). Methylphenidate has been rigorously
studied and found to be a safe and effective drug. However, there is a need for
pharmacological alternatives since there are patients and therapists who are
reluctant to use the drug. In some cases it is ineffective, others suffer from
intolerable side effects and still others need treatment extended for the entire
day. Recently, new pharmacological agents have been introduced for use in
Israel. This article discusses the use of these new psychostimulants as well as
other non-psychostimulant options. One of the new psychostimulants is Concerta,
a very long acting methylphenidate preparation, that has been shown to be very
effective. Adderall, a mixture of amphetamine salts, and Dexedrine
(dexamphetamine) are also widely used. This article also presents data on an
older psychostimulant, Cylert, Nitan (pemoline), prescribed until recently as a
major alternative for Ritalin but, at present, it is rarely used because of its
hepatotoxicity. Strattera (atomoxetine), a new non-stimulant drug, is a
selective noradrenaline reuptake inhibitor that is a promising therapeutic
option for children with ADHD. In summary, it is encouraging that there are
multiple pharmacological options for treating children with ADHD. There is no
one drug for all children and this is particularly important for children with
do not respond to methylphenidate. Last, but not least, the mere fact that the
new drugs are not called Ritalin, may play an important role in reducing the
irrational opposition to the pharmacological treatment of ADHD.
-----
Dev Med Child Neurol. 2005 Aug;47(8):539-45.
Effect of a social skills training group on everyday activities
of children with attention-deficit-hyperactivity disorder.
Gol D, Jarus T.
Jerusalem Child and Family Developmental Center, Jerusalem, Israel.
This preliminary study compared the daily living skills of children with and
without attention-deficit-hyperactivity disorder (ADHD), and the influence of a
social skills training group on these skills. Twenty-seven children with ADHD (2
females, 25 males; age range 5 to 8y, mean 6y 6mo, SD 10mo), and 24 children
without ADHD (8 females, 16 males; age range 5 to 8y, mean 6y 11mo, SD 10mo)
performed the Assessment of Motor and Process Skills (AMPS). Fourteen of the
children with ADHD used medication daily. Nine of the total group with ADHD were
randomly selected to attend group treatment which focused on social skills
training, through meaningful occupations (e.g. art, games, cooking). Children
were evaluated at the beginning of group treatment and after 10 sessions. Ten
children without ADHD were evaluated at similar intervals. Children with ADHD
initially achieved significantly lower scores on the AMPS in all process skills
(p<0.001) and in the coordination motor subtest (p<0.005) than children without
ADHD. Children with ADHD significantly improved from the first to the second
evaluation and no longer differed from the children without ADHD after treatment
(p<0.008). The results emphasize the need for a focus upon occupation in
assessment and treatment of children with ADHD.
-----
CNS Drugs. 2005;19(8):643-55.
Substance abuse in patients with attention-deficit hyperactivity
disorder : therapeutic implications.
Schubiner H.
Department of Internal Medicine, Providence Hospital, Southfield, Michigan
48075, USA. Howard.Schubiner@providence-stjohnhealth.org
Attention-deficit hyperactivity disorder (ADHD) is a common disorder in children
that frequently persists into adulthood. Studies have found that substance use
disorders (SUD) are seen more commonly in those with ADHD than the general
population. Although treatment with stimulant medications has been shown to be
effective for individuals with ADHD, concern about the use of these agents in
this population persists. This review article highlights the research in this
area with a focus on the treatment of individuals who present with concomitant
ADHD and SUD. Although stimulants can be abused, studies have shown that
adolescents who are prescribed stimulants for ADHD have lower rates of SUD than
those who are not treated with stimulants. It may be particularly difficult to
evaluate adults for the diagnosis of ADHD when SUD is a co-morbid factor.
Studies show that 20--30% of adults presenting with SUD have concomitant ADHD
and approximately 20--40% of adults with ADHD have histories of SUD. Therefore,
it is critical to perform careful diagnostic interviews to discern if patients
have either or both of these disorders. Many clinical experts suggest that
adults with ADHD and active SUD be treated for the SUD until a period of
sobriety persists prior to initiation of specific treatment for ADHD. Since
individuals with ADHD and active SUD are more likely to have more severe SUD and
a worse prognosis, this approach may not serve many patients, as they relapse
prior to obtaining ADHD treatment. Therefore, research has been directed towards
determining if the treatment of ADHD with stimulant medications can be safe and
effective for the individual with active SUD and concomitant ADHD. An initial
trial of methylphenidate in a population of adults with active cocaine
dependence and ADHD indicates that this is the case. Individuals with ADHD and
SUD can present difficult diagnostic and therapeutic challenges. It appears that
the most effective treatment option is to create a programme that uses the most
effective treatment modalities available, including both behavioural and medical
therapies, along with close supervision and monitoring. Newer medical treatment
options of long-acting stimulants and non-stimulants (e.g. atomoxetine) offer
effective treatment with a lower risk of abuse potential.
-----
Encephale. 2005 May-Jun;31(3):337-48.
[Atomoxetine: a new treatment for Attention Deficit/Hyperactivity
Disorder (ADHD) in children and adolescents]
[Article in French]
Purper-Ouakil D, Fourneret P, Wohl M, Reneric JP.
Service de Psychopathologie de l'Enfant et de l'Adolescent, Hopital Robert Debre,
boulevard Serurier, 75019 Paris.
This paper provides a review of safety and efficacy data as well as of
pharmacological characteristics of atomoxetine, a new drug treatment for the
Attention Deficit/Hyperactivity Disorder (ADHD). To date, the only
pharmacological treatment available in France for children and adolescents
diagnosed with ADHD is methylphenidate, a psychostimulant drug. However, the
clinical response to methylphenidate may be absent or insufficient in about
20-30% drug-treated children while the occurrence of adverse effects with
methylphenidate (sleep disturbances, loss of appetite, tics increase...) may
sometimes require a dose reduction or even the discontinuation of the treatment.
Atomoxetine is an alternative candidate drug for the treatment of ADHD. The drug
has been developed with respect to the actual standards of investigation of
drugs intended to a -pediatric use. Atomoxetine has been recently licensed in
the USA for the treatment of ADHD. Atomoxetine is a potent inhibitor of the
norepinephrine transporter that shows only mini-mal affinity for other
neurotransmitter systems. Although pharmacokinetics of atomoxetine is influenced
by the polymorphism of the CYP2D6 metabolic pathway, safety and -tolerability
data reported during clinical trials did not show any difference in poor versus
extensive metabolizers. In addition, atomoxetine does not inhibit nor induce the
CYP2D6 enzymatic function. The major metabolite of atomoxetine is
4-hydroxyatomoxetine, a pharmacologically active metabolic found in very low
plasma concentrations in pediatric patients, suggesting that it plays only a
minor role in the norepinephrine reuptake inhibition. Preliminary studies were
aimed to assess the effective dose range of atomoxetine and to evaluate its
safety and efficacy on the reduction of ADHD symptoms in adults and children
diagnosed with ADHD. Main data on the child and adolescent population were
obtained in four double-blind, randomized, placebo-controlled trials: two
identical pivotal trials, a multiple dose study, a once-daily dose study. The
first two pivotal trials were carried out in ADHD children aged 7-13 years,
treated with atomoxetine vs placebo for a duration of 9 weeks. Patients
presenting comorbidities (ie conduct disorder, -anxiety, depression) as well as
a history of previous treatment with methylphenidate were also eligible to
participate. The primary outcome was the reduction of the score on the ADHD
rating scale, ADHD-RS ; secondary criteria included the responder's rate
(patients with an ADHD-RS score reduction of 25% or above), the Clinical Global
Impression Scale and the Conners Parent Rating Scale. With a mean dose of 1.5
mg/kg/day, atomoxetine showed a significant reduction of mean ADHD-RS scores at
endpoint (ANOVA, p<0.001) (table II). Yet, the clinical significance of both
studies is limited since efficacy was scored only in a social/familial setting
and not in classroom conditions. In addition, intermediate results from baseline
to endpoint were not presented in the publication. The multiple dose trial
showed a significant reduction of the symptom score at the 1.2 and 1.8 mg/kg/day
doses. The objective of the last study was to assess the efficacy of a single
daily dose of atomoxetine versus placebo during a 6 week-treatment. Patients
were evaluated by parents, investigators, as well as by teachers. The
superiority of atomoxetine was demonstrated as compared to the placebo and the
effect size of the daily dosing was similar to that reported with multiple
doses.Preliminary data on ADHD patients presenting comorbidities showed that
atomoxetine alone signi-ficantly reduced the symptom scores of anxiety and
depression and similarly to atomoxetine associated with fluoxetine. In ADHD
children with the oppositional defiant disorder, oppositional symptoms were
reduced in the group receiving atomoxetine 1.8 mg/kg/day. Preliminary results in
children with ADHD and chronic tics or Tourette syndrome showed a significant
reduction of ADHD symptoms and a tendency to the decrease of tics.Tolerance and
safety data pooled from the child and adolescent trials were acceptable. Study
discontinuations due to adverse events in the four registration studies were
only 2.8%. The most frequent adverse effects reported were gastrointestinal
symptoms and decreased appetite. Weight loss reported early in clinical studies
tended to stabilize during the open-label extension phases lasting up to 9
months. A retrospective comparison showed that the adverse event profile of poor
metabolizers was similar to that of extensive metabolizers. In summary, data
presented suggest that atomoxetine is a safe and effective drug for the
treatment of ADHD in children and adolescents. Further studies are expected to
accurately define the place of atomoxetine in the treatment strategy of ADHD, a
chronic and invalidating disorder affecting 3 to 7% of school-aged children.
-----
J Am Acad Child Adolesc Psychiatry. 2005 Aug;44(8):748-55.
Comparison of risperidone and methylphenidate for reducing ADHD
symptoms in children and adolescents with moderate mental retardation.
Correia Filho AG, Bodanese R, Silva TL, Alvares JP, Aman M, Rohde LA.
Federal University of Rio Grande do Sul, Brazil.
OBJECTIVE: To evaluate the short-term efficacy and tolerability of risperidone
and methylphenidate for reducing symptoms related to
attention-deficit/hyperactivity disorder (ADHD) in children and adolescents with
moderate mental retardation. METHOD: In a 4-week, single-blind, parallel-group
trial, 45 subjects with moderate mental retardation and ADHD were randomized to
risperidone or methylphenidate and assessed using objective rating scales for
efficacy (SNAP [Swanson, Nolan, and Pelham]-IV and Nisonger Child Behavior
Rating Form) and side effects (Barkley's Side Effects Rating Scale and Udvalg
for Kliniske Undersogelser). RESULTS: Both groups had reduced ADHD symptoms
during the trial. Repeated-measures analysis of variance yielded a significant
effect for the interaction between time and group assignment in SNAP-IV Total
scores (F = 3.26; p = .05), suggesting a more pronounced effect for risperidone.
There was a significant weight reduction in the methylphenidate group and a
weight gain in the risperidone group. CONCLUSIONS: Our findings suggest that
risperidone is associated with greater reductions in ADHD Total score than
methylphenidate in children with moderate mental retardation and ADHD.
Comorbidity and the side effects profile might be of importance in choosing
between the medications, although it is usually prudent to try stimulants before
antipsychotics in such children.
-----
Expert Rev Neurother. 2005 Jul;5(4):525-39.
Clinical assessment and treatment of attention deficit hyperactivity disorder in
adults.
Asherson P.
MRC Social Genetic Developmental Psychiatry Centre, Institute of Psychiatry,
Kings College London, London, SE5 8AF, UK. p.asherson@iop.kcl.ac.uk
Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder
that frequently persists into adulthood, with significant levels of inattentive,
hyperactive and impulsive behavior. Impairments associated with adult ADHD
include distress from the symptoms, impaired ability to function in work and
academic settings, and problems sustaining stable relationships. The disorder is
commonly associated with volatile moods, antisocial behavior, and drug and
alcohol misuse. There is an increased risk of developing comorbid anxiety,
depression, personality disorders, and drug and alcohol dependence. Despite the
proven effectiveness of drugs such as methylphenidate, dexamphetamine and
atomoxetine, few cases of ADHD are recognized and treated in the UK. The reasons
for this are unclear, since most psychiatrists working with children and
adolescents are aware that ADHD commonly persists into adult life and they also
see the disorder affecting parents of children with ADHD. Issues of transition
from the care of child to adult psychiatry and the need to refer adult relatives
of children with ADHD to suitable psychiatric services are a major concern.
Furthermore, many cases of adult ADHD go unrecognized or are seen by mental
health teams that are not familiar with the subtleties of the adult
presentation. As a result, misdiagnosis and treatment for conditions such as
atypical depression, mixed affective disorder, cyclothymia, and borderline and
unstable emotional personality disorders is not uncommon. There is therefore a
requirement for further training in this area. This review will describe the
common clinical presentation and provide guidelines for the diagnosis and
treatment of ADHD in adults. Any psychiatrically trained physician using
standard psychiatric assessment procedures can perform clinical evaluations for
adult ADHD. As with other psychiatric disorders in adulthood, ADHD has its own
characteristic onset, course and psychopathology. Symptoms of ADHD are
trait-like, being stable characteristics from early childhood, and commonly
co-occur with affective instability. Stimulants are the mainstay of treatment
and are effective in around 70% of cases. Psychotherapeutic interventions also
have an important role. These guidelines will assist psychiatrists and other
adult mental health workers in identifying and treating individuals with adult
ADHD.
-----
Expert Rev Neurother. 2005 Jul;5(4):437-41.
Dexmethylphenidate extended-release capsules for attention
deficit hyperactivity disorder.
McGough JJ, Pataki CS, Suddath R.
David Geffen School of Medicine, 300 UCLA Medical Plaza, Suite 1414, Los
Angeles, CA 90095, USA. jmcgough@mednet.ucla.edu
Medications for attention deficit hyperactivity disorder (ADHD) currently
represent the ninth largest segment of the CNS market by sales, with 2.4 billion
USD spent annually on this condition and 40% annual growth. Stimulant
medications remain the most effective ADHD therapies and provide robust
improvement in ADHD symptoms in both youth and adults. Current prescribing
practices favor extended release preparations due to increased convenience,
compliance and tolerability with once-daily dosing. Dexmethylphenidate extended
release is a long-acting preparation of the ADHD medication Focalin (dexmethylphenidate
immediate release) and was approved for marketing by the US Food and Drug
administration in June 2005. Dexmethylphenidate consists of the single dextro-isomer
form of d,l-methylphenidate commonly marketed as Ritalin. Dexmethylphenidate
extended release utilizes spheroidal oral drug absorption system technology to
achieve a 50% immediate medication delivery and 50% delayed release of
dexmethylphenidate approximately 4 h after ingestion. Placebo-controlled,
clinical trials in children and adults with ADHD have demonstrated efficacy for
behavioral and academic ratings, with an analog classroom study showing
medication effects up to 12 h after dosing. Dexmethylphenidate extended release
was generally well tolerated with a side-effect profile similar to other
stimulants. The most common reported side effects include diminished appetite
and insomnia. Given its duration of effect, favorable tolerability and
flexibility in dosing, dexmethylphenidate extended release is likely to gain
considerable use as an ADHD treatment.
-----
Eur J Pediatr. 2005 Jul 27; [Epub ahead of print]
Homeopathic treatment of children with attention deficit
hyperactivity disorder: a randomised, double blind,
placebo controlled crossover trial.
Frei H, Everts R, von Ammon K, Kaufmann F, Walther D, Hsu-Schmitz SF, Collenberg
M, Fuhrer K, Hassink R, Steinlin M, Thurneysen A.
Swiss Association of Homeopathic Physicians SAHP, Lucerne, Switzerland.
An increasing number of parents turn to homeopathy for treatment of their
hyperactive child. Two publications, a randomised, partially blinded trial and a
clinical observation study, conclude that homeopathy has positive effects in
patients with attention deficit hyperactivity disorder (ADHD). The aim of this
study was to obtain scientific evidence of the effectiveness of homeopathy in
ADHD. A total of 83 children aged 6-16 years, with ADHD diagnosed using the
Diagnostic and Statistical Manual of Mental Disorders-IV criteria, were
recruited. Prior to the randomised, double blind, placebo controlled crossover
study, they were treated with individually prescribed homeopathic medications.
62 patients, who achieved an improvement of 50% in the Conners' Global Index
(CGI), participated in the trial. Thirteen patients did not fulfill this
eligibility criterion (CGI). The responders were split into two groups and
received either verum for 6 weeks followed by placebo for 6 weeks (arm A), or
vice-versa (arm B). At the beginning of the trial and after each crossover
period, parents reported the CGI and patients underwent neuropsychological
testing. The CGI rating was evaluated again at the end of each crossover period
and twice in long-term follow-up. At entry to the crossover trial, cognitive
performance such as visual global perception , impulsivity and divided
attention, had improved significantly under open label treatment ( P<0.0001).
During the crossover trial, CGI parent-ratings were significantly lower under
verum (average 1.67 points) than under placebo ( P =0.0479). Long-term CGI
improvement reached 12 points (63%, P <0.0001). Conclusion: The trial suggests
scientific evidence of the effectiveness of homeopathy in the treatment of
attention deficit hyperactivity disorder, particularly in the areas of
behavioural and cognitive functions.
-----
Lancet. 2005 Jul 16-22;366(9481):237-48.
Attention-deficit hyperactivity disorder.
Biederman J, Faraone SV.
Pediatric Psychopharmacology Unit of the Child Psychiatry Service, Massachusetts
General Hospital, and Harvard Medical School, Boston, MA 02114, USA. biederman@helix.mgh.harvard.edu
Attention-deficit hyperactivity disorder (ADHD) is a disorder of inattention,
impulsivity, and hyperactivity that affects 8-12% of children worldwide.
Although the rate of ADHD falls with age, at least half of children with the
disorder will have impairing symptoms in adulthood. Twin, adoption, and
molecular genetic studies show ADHD to be highly heritable, and other findings
have recorded obstetric complications and psychosocial adversity as predisposing
risk factors. Converging evidence from animal and human studies implicates the
dysregulation of frontal-subcortical-cerebellar catecholaminergic circuits in
the pathophysiology of ADHD, and molecular imaging studies suggest that
abnormalities of the dopamine transporter lead to impaired neurotransmission.
Studies during the past decade have shown the safety and effectiveness of new
non-stimulant drugs and long-acting formulations of methylphenidate and
amfetamine. Other investigations have also clarified the appropriate role of
targeted psychosocial treatments in the context of ongoing pharmacotherapy.
-----
J Long Term Eff Med Implants. 2005;15(4):389-400.
Advocating for students with learning disabilities and attention
deficit hyperactivity disorder in public schools.
Keegan NF, Brigham FJ, Cardellichio JM, Brigham MM.
Special Education Instructor, Albemarle County Schools, Charlottesville,
Virginia, USA.
Learning disabilities and attention deficit disorders are chronic conditions
that represent the most common diagnoses of students served in special education
programs in the schools. In this article, we discuss specific problem areas that
require decision advocacy on the part of the affected individual as well as his
or her family. We briefly describe the requirements for teachers who specialize
in this area of education as well as the nature of the conditions. We argue that
education programs for individuals with such conditions must be tailored to
offset the specific manifestations of the disability and its interactions with
the requirements of the educational system. We also note that educational
requirements are often dramatically different as students move from early
education through the system toward high school graduation and, for many, into
post-secondary education. We describe general procedures for advocacy that can
be used to enhance educational programs across the spectrum of school
placements. A section that specifically addresses advocacy for parents of
students with these types of disabilities acknowledges the critical role that
having a supportive parent plays in the development of successful education
programs. We then address the specific issues that are likely to characterize
educational problems at different levels of schooling. Among these are increased
requirements for self-management and self-discipline as students move through
the grades and increased emphasis on academic learning as students move into
middle and secondary schools. The article also discusses instructional methods
that are supported for students with such conditions as well as a brief
description of several types of treatment that are considered to be ineffective
for such students. Brief guidelines for recognizing both supported and
contra-indicated educational programs are also provided. We conclude with
resources for gathering information and making decisions that promote the
long-term interests of the affected child. As with other chronic conditions, the
probability of desirable outcomes is greatly enhanced by early and effective
planning.
-----
J Am Acad Child Adolesc Psychiatry. 2005 Jul;44(7):647-55.
A randomized, placebo-controlled study of once-daily atomoxetine
in the school setting in children with ADHD.
Weiss M, Tannock R, Kratochvil C, Dunn D, Velez-Borras J, Thomason C, Tamura R,
Kelsey D, Stevens L, Allen AJ.
University of British Columbia, Vancouver, Canada.
OBJECTIVE: Five studies have demonstrated the effectiveness of atomoxetine
compared with placebo in reducing symptoms of attention-deficit/hyperactivity
disorder (ADHD) based on parent reports. The primary objective of this clinical
trial was to assess the efficacy of once-daily atomoxetine compared with placebo
using teacher reports. METHOD: One hundred fifty-three patients aged 8-12 years
were randomly assigned to receive once-daily atomoxetine or placebo in a 2:1
ratio for 7 weeks. ADHD symptoms at school were primarily assessed by
baseline-to-endpoint change on the Attention-Deficit/Hyperactivity Disorder
Rating Scale-IV-Teacher Version: Investigator administered and scored (ADHDRS-IV-Teacher:Inv)
as rated by investigators using teacher reports. RESULTS: ADHDRS-IV-Teacher:Inv
total scores were significantly lower for children treated with atomoxetine
compared with those treated with placebo (p = .001). Similar results were
observed for the inattentive (p = .016) and hyperactive/impulsive (p < .001)
ADHDRS-IV-Teacher:Inv subscales, the clinician-rated Clinical Global Impressions
severity scale (p = .001), the Conners Global Index-Teacher scale (p = .008),
and the Conners Parent Rating Scale-Revised: Short Form ADHD Index T-Score (p <
.001). Discontinuations due to adverse events were low in both groups (atomoxetine
5.9%, placebo 0%, p = .096). CONCLUSIONS: This study extends previous results
based on parent reports showing that once-daily administration of atomoxetine is
safe and effective in improving ADHD symptoms in children and demonstrates that
outcomes at school are similar when symptoms are reported by teachers.
-----
Res Dev Disabil. 2005 Jun 11; [Epub ahead of print]
Effects of long-term psychostimulant medication on growth of
children with ADHD.
Zachor DA, Roberts AW, Bart Hodgens J, Isaacs JS, Merrick J.
Department of Pediatrics, Assaf Harofeh Medical Center, Sackler School of
Medicine, Tel Aviv University, IL-70300 Zerifin, Israel.
The objective was to assess the effects of long-term psychostimulant medication
on growth parameters in children with attention deficit hyperactivity disorder
(ADHD). Eighty-nine children diagnosed with ADHD treated by prescribed
psychostimulant medications were followed with repeated growth measures over a 3
years duration. Anthropometric measurements were recorded at baseline, 3, 6, 12,
24, and 36 months. Medical records were reviewed for demographic information,
medication side effects and appetite suppression. Body mass index (BMI) and
z-scores were determined at each follow up visit. Descriptive and analytical
analyses by repeated measures analysis of varianc were performed. Significant
weight loss was documented mostly during the first few months of treatment with
stimulants. Although z-scores for weight showed significant changes over the 2
years of treatment, further analysis of the changes did not reach clinical
significance. BMI growth was within normal limits throughout the duration of
treatment. Baseline weight predicted weight loss for heavier children only.
Pre-pubertal children were more subject to weight loss than children during
puberty, as well as children for which appetite suppression was reported. No
long-term impact on height was noted. Different stimulant medication did not
differ in their effects on growth. Generally, parents and providers can be
reassured that growth changes with long-term stimulant therapy are not
clinically significant for a diverse group of children with ADHD.
-----
Expert Opin Pharmacother. 2005 Jun;6(6):1003-18.
Safety, efficacy and extended duration of action of mixed
amphetamine salts extended-release capsules for the treatment of ADHD.
Weisler RH.
Department of Psychiatry, Duke University Medical Center, 700 Spring Forest Rd.
Suite 125, Raleigh, NC 27609, USA. rweisler@aol.com
Stimulant medications have proven to be effective in reducing the core symptoms
of hyperactivity, impulsivity and inattention and are considered the first line
of therapy for patients with attention-deficit/hyperactivity disorder (ADHD).
Mixed amphetamine salts extended-release capsules (MAS XR; Adderall XR, Shire
Pharmaceuticals Group) include immediate-release pellets of mixed amphetamine
salts that release the first half of the dose upon ingestion and delayed-release
pellets that begin to release active drug approximately 4 h later. The MAS XR
capsule contains the same 3:1 ratio of dextroamphetamine to levoamphetamine as
do mixed amphetamine salts immediate-release tablets (MAS IR; Adderall), Shire
Pharmaceuticals Group), and the bioavailability and pharmacokinetic profiles of
MAS XR 20 mg are comparable to those with MAS IR 10 mg b.i.d. MAS XR has a rapid
onset of action--within 1.5 h--and provides 12 h coverage. The efficacy, safety
and extended duration of action of MAS XR have been established through clinical
studies in school-age children, adolescents and adults.
-----
J Am Acad Child Adolesc Psychiatry. 2005 May;44(5):428-433.
Six-Week Open-Label Reboxetine Treatment in Children and
Adolescents With Attention-Deficit/Hyperactivity Disorder.
Ratner S, Laor N, Bronstein Y, Weizman A, Toren P.
Drs. Ratner, Laor, Bronstein, and Toren are with the Tel Aviv-Brull Community
Mental Health Center, Israel; Dr. Weizman is with the Geha Mental Health Center
and the Felsenstein Medical Research Center, Petah Tiqva, Israel; Drs. Laor,
Weizman, and Toren are with the Sackler Faculty of Medicine, Tel Aviv
University; Dr. Laor is with the Yale Child Study Center, New Haven, CT.
OBJECTIVE:: This open-label study assessed the effectiveness of reboxetine, a
selective norepinephrine reuptake inhibitor, in children and adolescents with
attention-deficit/hyperactivity disorder (ADHD) resistant to a previous
methylphenidate trial. METHOD:: Thirty-one child and adolescent outpatients,
aged 8 to 18 (mean age, 11.7; SD = 2.87) years, diagnosed with ADHD were
enrolled in a 6-week open-label study. Assessments included rater-administered
scales (DSM-IV ADHD Scale; Clinical Global Impressions Scale),
parent-administered scales (the Abbreviated Conners Rating Scale), and
self-administered-scales for the evaluation of depressive (Children's Depression
Inventory) and anxiety (the Revised Children's Manifest Anxiety Scale) symptoms.
Reboxetine was initiated and maintained at a dose of 4 mg/day. RESULTS:: A
significant decrease in ADHD symptoms, on all scales measured, was noted.
Adverse effects were relatively mild and transient. The most common adverse
effects were drowsiness/sedation and gastrointestinal complaints. CONCLUSIONS::
The results of the current open-label study suggest the effectiveness of
reboxetine in the treatment of ADHD in methylphenidate-resistant children and
adolescents. Double-blind, placebo-, and active comparator-controlled studies
are indicated to rigorously test the efficacy of reboxetine in ADHD.
-----
J Am Acad Child Adolesc Psychiatry. 2005 May;44(5):418-427.
Sequential Pharmacotherapy for Children With Comorbid
Attention-Deficit/Hyperactivity and Anxiety Disorders.
Abikoff H, McGough J, Vitiello B, McCracken J, Davies M, Walkup J, Riddle M,
Oatis M, Greenhill L, Skrobala A, March J, Gammon P, Robinson J, Lazell R,
McMahon DJ, Ritz L; and The RUPP ADHD/ANXIETY STUDY GROUP.
>From Columbia University at the New York State Psychiatric Institute, New York
(M.D., L.G., A.S.); Duke University Medical Center, Durham, NC (J.M., P.G.);
Johns Hopkins University, Baltimore, MD (J.W., M.R.); Nathan S. Kline Institute
for Psychiatric Research, Orangeburg, NY (J.R., R.L., D.M.); National Institute
of Mental Health, Bethesda, MD (B.V., L.R.); New York University Child Study
Center, New York (H.A, M.O.); University of California Los Angeles (J.Mc., J.Mc.).
OBJECTIVE:: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied
by clinically significant anxiety, but few empirical data guide treatment of
children meeting full DSM-IV criteria for ADHD and anxiety disorders (ADHD/ANX).
This study examined the efficacy of sequential pharmacotherapy for ADHD/ANX
children. METHOD:: Children, age 6 to 17 years, with ADHD/ANX were titrated to
optimal methylphenidate dose and assessed along with children who entered the
study on a previously optimized stimulant. Children with improved ADHD who
remained anxious were randomly assigned to 8 weeks of double-blind stimulant +
fluvoxamine (STIM/FLV) or stimulant + placebo (STIM/PL). Primary efficacy
measures were the Swanson, Nolan, Atkins, and Pelham IV Parent and Teacher
Rating Scale ADHD score and the Pediatric Anxiety Rating Scale total score.
ADHD, ANX, and overall Clinical Global Impressions-Improvement scores were also
obtained. RESULTS:: Of the 32 medication-naive children openly treated with
methylphenidate, 26 (81%) improved as to ADHD. Twenty-five children entered the
randomized trial. Intent-to-treat analysis indicated no differences between the
STIM/FLV (n = 15) and STIM/PL groups on the Pediatric Anxiety Rating Scale or
Clinical Global Impressions-Improvement-defined responder rate. Medications in
both arms were well tolerated. CONCLUSIONS:: Children with ADHD/ANX have a
response rate to stimulants for ADHD that is comparable with that of children
with general ADHD. The benefit of adding FLV to stimulants for ANX remains
unproven.
-----
Biol Psychiatry. 2005 Apr 1;57(7):793-801.
Bupropion XL in adults with attention-deficit/hyperactivity
disorder: a randomized, placebo-controlled study.
Wilens TE, Haight BR, Horrigan JP, Hudziak JJ, Rosenthal NE, Connor DF, Hampton
KD, Richard NE, Modell JG.
Pediatric Psychopharmacology Research, Yawkey Center for Outpatient Care,
Massachusetts General Hospital, Boston, Massachusetts 021143-3117, USA. twilens@partners.org
BACKGROUND: Data remain limited on treatment strategies for adults with
attention-deficit/hyperactivity disorder (ADHD). This study evaluated the
efficacy and safety of an extended-release, once-daily formulation of bupropion
(XL) in the treatment of adults with ADHD. METHODS: This multisite,
placebo-controlled, 8-week prospective trial evaluated 162 adult patients
diagnosed with ADHD (combined and inattentive types). Subjects were treated with
up to 450 mg/day of bupropion XL. The primary efficacy endpoint was the
proportion of ADHD responders (defined as at least a 30% reduction in the
investigator-rated ADHD Rating Scale score) at week 8 (last observation carried
forward [LOCF]). RESULTS: Bupropion XL responders (53%) exceeded placebo
responders (31%) (p =.004 at week 8) with a significantly greater proportion of
bupropion XL responders as early as week 2 (p = .01). Treatment effect size
calculated for the ADHD Rating Scale total score was .6. Bupropion XL appeared
to provide sustained benefit throughout the day compared with placebo (morning p
=.033, afternoon p =.004, evening p = .024). Bupropion XL was safe and well
tolerated, with no serious or unexpected adverse events and a low rate of
drug-related study discontinuation (5%). CONCLUSIONS: The results from this
multisite study indicate that bupropion XL is an effective and well-tolerated
nonstimulant treatment for adult ADHD.
-----
Cochrane Database Syst Rev. 2005 Apr 18;(2):CD005042.
Family therapy for attention-deficit disorder or
attention-deficit/hyperactivity disorder in children and adolescents.
Bjornstad G, Montgomery P.
Social Policy and Social Work, University of Oxford, Wolfson College, Linton
Road, Oxford, Oxon, UK, OX2 6UD.
BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is diagnosed in
between 3% and 7% of school-age children and consists of the core symptoms of
inattention, impulsivity and hyperactivity. Children are often treated with
medication, usually stimulant medication such as methylphenidate. Stimulant
medication has been found to be effective for alleviating ADHD symptoms, at
least in the short term. ADHD is also treated with a variety of psychosocial and
psychoeducational interventions for parents, children, and with multicomponent
interventions combined with medication management. However, many patients (10 to
13% of patients) cannot or prefer not to take medication. Family therapy without
medication may help to develop structure in the family, help to manage
children's behaviour, and may help families cope with distress from the presence
of the disorder. OBJECTIVES: This review seeks to address the question of
whether family therapy without medication can reduce the core symptoms of ADHD
as compared to no treatment or standard treatment. SEARCH STRATEGY: The
following electronic databases were searched using a specific search strategy:
The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue
3, 2004), MEDLINE (1966 to April 2004), PsycINFO (1872 to April 2004), CINAHL
(1982 to April 2004), Biosis (Biological Abstracts) (1985 to March 2004),
Dissertation Abstracts (1980 to April 2004), and Sociological Abstracts (Sociofile)
(1963 to April 2004). Hand searches of relevant journals and bibliographies were
also conducted and experts in the field were contacted for further information.
SELECTION CRITERIA: Included studies were randomised controlled trials
investigating the efficacy of behavioural family therapy, cognitive behavioural
family therapy, or functional family therapy for children with ADHD or ADD
(Attention Deficit Disorder). DATA COLLECTION AND ANALYSIS: Studies were
evaluated for methodological quality and to determine whether they met the
inclusion criteria. MAIN RESULTS: This assessment yielded two studies. Data were
extracted for both studies. The findings from Jensen 1999 (N=579) indicate that
no difference can be detected between the efficacy of behavioural family therapy
and treatment as usual in the community. The finding from the available data
from Horn 1991 slightly favours treatment over medication placebo. AUTHORS'
CONCLUSIONS: Further research examining the effectiveness of family therapy
versus a no-treatment control condition is needed to determine whether family
therapy is an effective intervention for children with ADHD. There were no
results available from studies investigating forms of family therapy other than
behavioural family therapy.
-----
Curr Opin Pediatr. 2005 Apr;17(2):265-74.
Update: attention deficit/hyperactivity disorder in the primary
care office.
Schonwald A.
Children's Hospital, Boston, Harvard Medical School, Boston, Massachusetts
02115, USA. alison.schonwald@childrens.harvard.edu
PURPOSE OF REVIEW: Attention-deficit/hyperactivity disorder (AD/HD) affects 7.5%
of children, making it among the more common behavioral disorders of childhood.
Pediatricians increasingly are expected to recognize AD/HD, as well as diagnose
and manage it in the primary care setting. This article reviews recent
developments in the care of the pediatric AD/HD patient, with emphasis on
information enhancing primary care management. RECENT FINDINGS: Studies
published in 2004 provide evidence to guide the treatment of AD/HD. The AD/HD
literature continues to support the important role of genetics in its etiology.
The absence of universal genetic or neuroimaging findings indicates that history
from multiple sources and physical exam remain the standard diagnostic method.
Comorbid medical problems, such as sleep disruption and growth suppression,
continue to be better understood in the setting of AD/HD, as do the substantial
impacts of comorbid learning and psychiatric disorders. Despite great interest
in alternative, nonstimulant and behavioral treatments, methylphenidate and
amphetamine-based medications remain the mainstay of AD/HD intervention.
SUMMARY: AD/HD is a common medical condition with implications for long-term
safety and life function, such as academic success, accident occurrence, and
drug use. Identification and treatment is increasingly based in the primary care
office, where children must be monitored for co-occurring disorders and referred
for additional supports when necessary. Tools and guidelines provided by the
American Academy of Pediatrics (AAP) provide a framework for consistent and
competent AD/HD care supported by current evidence.
-----
J Clin Psychiatry. 2005 Mar;66(3):294-9.
Long-term, open-label study of the safety and efficacy of
atomoxetine in adults with attention-deficit/hyperactivity disorder: an interim
analysis.
Adler LA, Spencer TJ, Milton DR, Moore RJ, Michelson D.
New York University, New York, USA.
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is an early-onset
neuropsychiatric disorder that affects 3% to 7% of school-age children and 4% of
adults. Its pathophysiology is thought to involve the dopaminergic and
nor-adrenergic pathways associated with attention control and impulsivity. These
symptoms have largely been defined in the childhood population, but the course
of the condition and expression in the adult population are not as well
characterized. METHOD: This is an ongoing, 3-year, open-label study consisting
of adults with DSM-IV ADHD who were previously enrolled in 1 of 2 double-blind,
acute-treatment studies of atomoxetine. The results of the interim analysis
reported here were derived from the study of 384 patients at 31 sites who had
been studied for a period of up to 97 weeks. The primary efficacy measure was
the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV)
total ADHD symptom score. In addition, safety, adverse events, and vital sign
measurements were assessed. RESULTS: Significant improvement was noted with
atomoxetine therapy, with mean CAARS-Inv:SV total ADHD symptom scores decreasing
33.2% from 29.2 (baseline of open-label therapy) to 19.5 (endpoint of open-label
therapy) (p < .001). Similar and significant decreases were noted for the
secondary efficacy measures. Adverse events consisted primarily of
pharmacologically (noradrenergic) expected effects, such as increases in heart
rate and blood pressure and a slight decrease in weight. CONCLUSION: The results
of this interim analysis of an ongoing, open-label study of adults with ADHD
support the long-term efficacy, safety, and tolerability of atomoxetine for the
treatment of adult ADHD.
-----
Expert Rev Neurother. 2005 Jan;5(1):107-121.
Treatment of attention deficit hyperactivity disorder in adults.
Greenfield B, Hechman L.
Montreal Childrens Hospital , Emergency Follow-Up Team, 2300 Tupper Ave,
Montreal, Quebec, H3H 1P3, Canada Tel.: +1 514 412 4400 ext. 22785
brian.greenfield@muhc.mcgill.ca.
A number of medication and psychologic treatment options for adults with
attention deficit hyperactivity disorder have become available during the past 5
years, while others are under investigation. This review describes the safety
and effectiveness of the stimulants (i.e., methylphenidate and dexedrine), and
particularly the newer long-acting stimulants (i.e., Concerta((R)) and Adderall
XR((R))) in the treatment of this population. Some nonstimulant/nonantidepressants,
particularly atomoxetine, have also been shown to improve attention deficit
hyperactivity disorder symptoms. Combination treatment of stimulants and
antidepressants require more study with regard to safety and efficacy.
Psychosocial interventions (e.g., cognitive behavioral therapy, mindfulness
training and cognitive remediation) can also benefit adults with attention
deficit hyperactivity disorder. Cognitive behavioral therapy combined with
medication is more effective than either intervention alone, especially for
addressing the emotional and functional aspects of peoples lives and thus
improving occupational, interpersonal and emotional outcomes.
-----
Am J Psychiatry. 2005 Jan;162(1):58-64.
Randomized, placebo-controlled trial of mixed amphetamine salts
for symptoms of comorbid ADHD in pediatric bipolar disorder after mood
stabilization with divalproex sodium.
Scheffer RE, Kowatch RA, Carmody T, Rush AJ.
Department of Psychiatry, UT Southwestern Medical Center, 5323 Harry Hines
Blvd., Dallas, TX 75390-8589. john.rush@utsouthwestern.edu.
OBJECTIVE: The purpose of this study was to determine whether adjunctive use of
a psychostimulant (mixed amphetamine salts) was safe and efficacious for
treatment of symptoms of attention deficit hyperactivity disorder (ADHD) in
pediatric outpatients with bipolar I or bipolar II disorder and concurrent ADHD
whose manic symptoms had been stabilized through treatment with divalproex
sodium. METHOD: An 8-week open-label trial of divalproex sodium to control manic
symptoms and to discern the effect of divalproex sodium on ADHD was followed by
a 4-week randomized, double-blind, placebo-controlled crossover trial to
determine if mixed amphetamine salts was safe and effective for treatment of
ADHD symptoms. Patients in the crossover trial continued to receive divalproex
sodium. Diagnoses, made by clinical interview, were confirmed with the
Washington University in St. Louis Kiddie Schedule for Affective Disorders and
Schizophrenia. The Young Mania Rating Scale (for manic symptoms) and the
Clinical Global Impression of improvement (for ADHD symptoms) were the primary
outcome measures. RESULTS: Forty subjects ages 6-17 years with bipolar I
disorder (77.5%) or bipolar II disorder (22.5%) and a Young Mania Rating Scale
score >/=14 entered open treatment with divalproex sodium. With divalproex
sodium, 32 subjects achieved >/=50% reduction in Young Mania Rating Scale
baseline scores, but only three participants had significant improvement in ADHD
symptoms. For the 30 subjects who entered the placebo-controlled crossover
trial, mixed amphetamine salts was significantly more effective than placebo for
ADHD symptoms. No significant side effects or worsening of manic symptoms was
observed. CONCLUSIONS: Pediatric patients with bipolar disorder and concurrent
ADHD can be safely and effectively treated with mixed amphetamine salts after
their manic symptoms are stabilized with divalproex sodium. Divalproex sodium
alone (8-week trial) is not an effective treatment for ADHD in the context of
bipolar disorder.
-----
J Child Adolesc Psychopharmacol. 2004 Fall;14(3):418-25.
Selegiline in comparison with methylphenidate in attention
deficit hyperactivity disorder children and adolescents in a double-blind,
randomized clinical trial.
Mohammadi MR, Ghanizadeh A, Alaghband-Rad J, Tehranidoost M, Mesgarpour B, Soori
H.
Department of Psychiatry, Tehran University of Medical Sciences, Psychiatry and
Clinical Psychology Research Center, Roozbeh Hospital, Tehran, Iran., National
Research Center for Medical Sciences (NRCMSI), Tehran, Iran.
Objectives: The aim of this study was to examine the selegiline treatment
compared to methylphenidate (MPH) in children and adolescents with attention
deficit hyperactivity disorder (ADHD). Method: Forty subjects, aged 6-15 years,
boys and girls, who were diagnosed as having ADHD, using the criteria of the
Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV),
were randomly assigned to receive either selegiline or MPH for 60 days.
Treatment outcomes were assessed using the Attention Deficit Hyperactivity Scale
(ADHS) administered at baseline and on days 14, 28, 42, and 60 following the
commencement of treatment. Side effects were also rated. Results: There were no
significant differences between sex, age, weight, and ethnicity of participants
in the 2 groups. Both groups showed a significant improvement over the 60 days
of treatment resulting from the teachers' and parents' ADHS scores across the
treatment. Conclusion: Following the trial, MPH did not effect greater mean
improvement as a result of the parents' or teachers' ADHS scores than selegiline.
Thus, selegiline appears to be effective and well tolerated for ADHD in children
and adolescents.
-----
J Child Adolesc Psychopharmacol. 2004 Fall;14(3):372-94.
Second-generation antipsychotic medications in children and
adolescents.
Cheng-Shannon J, McGough JJ, Pataki C, McCracken JT.
Department of Psychiatry, University of Washington School of Medicine, Seattle,
Washington.
Objective: We reviewed available pediatric literature on second-generation
antipsychotic medications to assess current evidence of efficacy and safety.
Method: An English language MEDLINE search (1974-2003) was conducted using key
words-atypical antipsychotics, children and adolescents, toxicity, clozapine,
risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole. Additional
efficacy and safety data were obtained from drug manufacturers. Results: We
identified 176 reports, including 15 double-blind, controlled trials, 58
openlabel studies, 18 retrospective chart reviews, and 85 case series/reports.
The majority of these studies (43%) were of risperidone. Evidence suggests that
second-generation antipsychotics are efficacious in the treatment of psychosis,
bipolar disorders, pervasive developmental disorders, and Tourette's Disorder,
and are potentially useful in mental retardation, conduct disorder, and severe
attention deficit hyperactivity disorder (ADHD). The most frequently reported
side effects included cardiovascular effects, weight gain, sedation, sialorrhea,
extrapyramidal signs, and hyperprolactinemia, although the relative frequencies
of these untoward effects vary among medications. Conclusion: Although the
evidence base for pediatric use of second-generation antipsychotics is
expanding, the majority of available studies are anecdotal, or short-term,
openlabel trials. Reports suggest that these compounds are effective for a
variety of psychiatric disorders in children and adolescents, but additional
double-blind, controlled studies are required to establish definitive efficacy.
Although these medications appear to be well tolerated in short-term studies,
long-term follow-up investigations and ongoing clinical monitoring are necessary
to confirm their safety in this age group.
-----
Am J Health Syst Pharm. 2004 Nov 15;61(22):2391-9.
Atomoxetine: the first nonstimulant for the management of
attention-deficit/hyperactivity disorder.
Corman SL, Fedutes BA, Culley CM.
Drug Information Center, University of Pittsburgh Medical Center, Pittsburgh, PA
15213, USA.
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety, drug
interactions, dosage and administration, and place in therapy of atomoxetine in
the treatment of attention-deficit/hyperactivity disorder (ADHD) are reviewed.
SUMMARY: Atomoxetine is a methylphenoxy-benzenepropanamine derivative with
antidepressant activity and is thought to enhance noradrenergic function via
selective inhibition of the presynaptic norepinephrine transporter. Atomoxetine
is rapidly absorbed from the gastrointestinal tract, reaching peak levels in
1.83 hours in pediatric patients and 1-1.5 hours in adults. The clinical
efficacy of atomoxetine in the treatment of ADHD has been evaluated in six
published clinical trials of children and adolescents and two studies enrolling
only adults. Clinical trial data indicate that atomoxetine is safe and well
tolerated for the treatment of ADHD; however, safety data about long-term use
(greater than one year) are unavailable. Adverse events reported in clinical
trials were mainly mild to moderate and transient in nature. Recommended dosing
of atomoxetine is weight based, and dosages should be adjusted to a target
dosage of 1.2 mg/kg/day in children and adolescents weighing 70 kg or less and
to 80 mg/day in children and adolescents weighing over 70 kg and adults. While
current guidelines from the American Academy of Pediatrics recommend stimulants
and behavior modification as first-line therapy for the management of ADHD,
atomoxetine offers those patients who do not respond to or cannot tolerate one
or more stimulants an alternative treatment option. CONCLUSION: Atomoxetine, the
first non-stimulant approved for the management of ADHD in children,
adolescents, and adults, provides patients who have not responded to or cannot
tolerate one or more stimulants an alternative treatment option.
-----
Expert Opin Emerg Drugs. 2004 Nov;9(2):293-302.
New drugs for the treatment of attention-deficit/hyperactivity
disorder.
Pataki CS, Feinberg DT, McGough JJ.
UCLA Neuropsychiatric Institute, Room 27-370C, 760 Westwood Plaza, Los Angeles,
CA 90024, USA. cpataki@mednet.ucla.edu
Attention-deficit/hyperactivity disorder (ADHD) is the most common
neuropsychiatric disorder of childhood. Recent research indicates that ADHD most
often persists into adolescence and adulthood, and is associated with
impairments in academic, social and occupational functioning. The ADHD diagnosis
is based on history and clinical examination. There are no objective laboratory
measures for diagnosis. ADHD is largely heritable. Its underlying
pathophysiology has been theorised to include dysregulation of inhibitory
noradrenergic frontocortical activity on dopaminergic striatal structures.
Evidence shows that ADHD is highly responsive to pharmacological treatments
resulting in global functional improvements. Although pharmacotherapy is
recognised as the most effective treatment, additional components to optimise
ADHD management include proper educational placement, parent management training
and social skills development. Central nervous system stimulants, specifically
methylphenidate and amphetamine, remain first-line pharmacological treatments.
Atomoxetine, a selective noradrenergic re-uptake inhibitor, is the first
non-stimulant compound to receive FDA approval for paediatric and adult ADHD.
Other medication classes, including alpha-agonist antihypertensives, tricyclic
antidepressants, other antidepressants such as buproprion, and the
wake-promoting agent modafinil, are prescribed in off-label therapy. Ongoing
development of new ADHD medications is expected to emphasise alternative and
extended-release delivery systems and non-stimulant compounds.
-----
CNS Drugs. 2004;18(14):957-66.
The role of stimulants in the treatment of preschool children
with attention-deficit hyperactivity disorder.
Kratochvil CJ, Greenhill LL, March JS, Burke WJ, Vaughan BS.
University of Nebraska Medical Center, Omaha, Nebraska 68198-5581, USA.
The symptoms of attention-deficit hyperactivity disorder (ADHD) can have an
early onset, beginning before the age of 6 years. Despite the significant number
of preschool-aged children that can be diagnosed with ADHD, there are limited
controlled data available on the pharmacological interventions being
increasingly used in this population. A 1990 review showed that 34% of
paediatricians and 15% of family physicians had prescribed psychostimulant
medications to preschoolers with ADHD, and pharmacoepidemiological studies
indicate growing use of stimulants in preschoolers during the 1990s.
Unfortunately, only six controlled trials, with a total enrollment of less than
200 children, have been conducted using these drugs in preschoolers. While these
small studies provide some evidence of benefit from the use of methylphenidate
in preschoolers with ADHD, more data are critically needed.Practice parameters
developed by the American Academy of Child & Adolescent Psychiatry and the
American Academy of Pediatrics provide some guidance regarding the diagnosis and
treatment of young children with ADHD, but are mainly based upon research in
children of primary-school age. The ongoing PATS (Preschool ADHD Treatment
Study), funded by the National Institute of Mental Health, will provide
important clinical guidance for diagnostic considerations and intervention
strategies for children with ADHD aged 3-5 years. Pending the release of data
from the PATS study, clinicians must rely on developmental assessment skills,
available standardised rating instruments, reports about the child from multiple
informants, and knowledge of the risks and benefits of available pharmacological
and behavioural treatments, in order to treat preschool children with ADHD
effectively.
-----
Fortschr Neurol Psychiatr. 2004 Oct;72(10):586-91.
[Atomoxetine for the treatment of attention-deficit/hyperactivity
disorder]
[Article in German]
Davids E, Gastpar M.
Klinik fur Psychiatrie und Psychotherapie der Universitat Duisburg-Essen,
Rheinische Kliniken Essen, Essen. eugen.davids@uni-essen.de
Atomoxetine is a selective noradrenaline reuptake inhibitor that has been
studied for use in the treatment of attention-deficit/hyperactivity disorder
(ADHD). In vitro, ex vivo and in vivo studies have shown that atomoxetine is a
highly selective antagonist of the presynaptic norepinephrine transporter with
little or no affinity for other noradrenergic receptors or other
neurotransmitter transporters or receptors. So far, two open-label and seven
randomised, double-blind, placebo-controlled, clinical trials have been
published, six in youths and three in adults. Each of these trials has shown a
positive response as measured by the primary efficacy measures, the ADHD-IV
Rating Scale (ADHD RS) or the Conners Adult ADHD Rating Scale (CAARS).
Atomoxetine has generally been well tolerated. The most common treatment-related
adverse event was decreased appetite. Atomoxetine shows no abuse potential and
is not a controlled substance in the US. In November of 2002 the FDA approved
atomoxetine for use in the US for the treatment of ADHD in children, adolescents
and adults. Atomoxetine is the first nonstimulant approved by the FDA for the
treatment of ADHD and the first medication approved for the treatment of adult
ADHD.
-----
J Child Neurol. 2004 Oct;19(10):798-814.
Attention-deficit hyperactivity disorder (ADHD).
Voeller KK.
Western Institute for Neurodevelopmental Studies and Interventions, Boulder, CO
80302, USA. kvoeller@worldnet.att.net
Approaches to the diagnosis and treatment of attention-deficit hyperactivity
disorder (ADHD) are undergoing a major change as a result of information from
studies on the genetics of ADHD and the use of new neuroimaging technologies.
Moreover, pharmacogenomics, although still in its infancy, will provide a basis
for much more sophisticated treatment strategies for ADHD, particularly once
more information is available about the genetics of ADHD. Even at this point in
time, there is some pertinent information available that, although not ready for
application in clinical settings, nonetheless provides a broader perspective for
the clinician. In terms of etiology, ADHD is a neuropsychiatric disorder. There
is a genetic basis in about 80% of the cases, involving a number of different
genes, and in about 20% of the cases, ADHD is the result of an acquired insult
to the brain. Some individuals likely have both genetic and acquired forms.
Although medication works well in many cases of ADHD, optimal treatment of ADHD
requires integrated medical and behavioral treatment. The family plays a crucial
role in the management of children with ADHD. Because there is often a very high
degree of comorbidity between ADHD and learning disabilities, teachers also have
a great deal to contribute in the day-to-day management of these children. Early
recognition and treatment prevent the development of more serious
psychopathology in adolescence and adulthood.
-----
Psychol Med. 2004 Aug;34(6):973-82.
Efficacy and safety of methylphenidate in 45 adults with
attention-deficit/hyperactivity disorder. A randomized placebo-controlled
double-blind cross-over trial.
Kooij JJ, Burger H, Boonstra AM, Van der Linden PD, Kalma LE, Buitelaar JK.
Parnassia, Psycho-medical Centre, Department of Adult ADHD, The Hague, The
Netherlands. s.kooij@parnassia.nl
BACKGROUND: Data on the efficacy and safety of methylphenidate in adults with
attention deficit/ hyperactivity disorder (ADHD) are lacking in Europe. This
study was undertaken to report on the efficacy and safety of methylphenidate in
an adult out-patient population with ADHD, and to compare results with US data.
METHOD: A double-blind randomized cross-over trial comparing methylphenidate and
placebo in 45 adults with ADHD with childhood onset was performed in a
dose-titration design. Methylphenidate was titrated from 0.5 mg/kg per day in
week 1 up to 1.0 mg/kg per day in week 3. RESULTS: Response rates using
methylphenidate varied between 38 and 51%, and using placebo between 7 and 18%
(p<0.05), depending on outcome measure used. Although the overall percentage of
subjects having any side effect on both methylphenidate and placebo was rather
high, side effects on methylphenidate over and above those on placebo were few
and mild. CONCLUSIONS: Methylphenidate proves to be an effective and well
tolerated treatment for symptoms of ADHD in adults in the short term. Future
research should study the long-term response and clarify the impact of gender,
co-morbidity, socio-economic status and IQ on response rates in adults with
ADHD.
-----
Arch Intern Med. 2004 Jun 14;164(11):1221-6.
Attention-deficit/hyperactivity disorder in adults: a survey of
current practice in psychiatry and primary care.
Faraone SV, Spencer TJ, Montano CB, Biederman J.
Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston, MA
02114, USA. sfaraone@hms.harvard.edu
BACKGROUND: Recognition and treatment of attention-deficit/hyperactivity
disorder (ADHD) in adults in psychiatry and primary care have faced many
obstacles. METHODS: Review by 50 psychiatrists and 50 primary care practitioners
(PCPs) of 537 and 317 medical records, respectively, of adults diagnosed as
having ADHD. Information on other psychiatric disorders, time of onset of ADHD,
source of referral, use of referrals for diagnosis, ADHD treatment, and use of
drug holidays was recorded. RESULTS: Forty-five percent of the patient records
reviewed by psychiatrists and 65% reviewed by PCPs indicated previous diagnoses
of ADHD. Only 25% of the adults with ADHD had been first diagnosed as having the
disorder in childhood or adolescence. A diagnosis of ADHD was the initial cause
for referral in 80% of psychiatric patients and 60% of PCP patients. Most
patients with previously diagnosed and undiagnosed ADHD were self-referred.
Among patients who had not received a prior diagnosis, 56% complained about ADHD
symptoms to other health professionals without being diagnosed; PCPs were the
least aggressive in diagnosing ADHD. In psychiatric and PCP settings, there was
a statistical difference in the use of pharmacotherapy (91% vs 78%,
respectively) and the proportion of patients taking drug holidays (24% vs 17%,
respectively); most drug holidays were initiated by the patient (57%).
Stimulants were the treatment of choice for adult ADHD (84% treated with
stimulants). CONCLUSION: Data contained within this medical record review
suggest that adult ADHD is a substantial source of morbidity in both psychiatric
and PCP settings.
-----
J Am Acad Child Adolesc Psychiatry. 2004 Jun;43(6):686-98.
Effects of methylphenidate treatment in children with mental
retardation and ADHD: individual variation in medication response.
Pearson DA, Lane DM, Santos CW, Casat CD, Jerger SW, Loveland KA, Faria LP,
Mansour R, Henderson JA, Payne CD, Roache JD, Lachar D, Cleveland LA.
Department of Psychiatry and Behavioral Sciences, University of Texas Medical
School at Houston 77030-3497, USA. Deborah.A.Pearson@uth.tmc.edu
OBJECTIVE: Individual variation in cognitive and behavioral response to
methylphenidate (MPH) was investigated in children with mental retardation and
attention-deficit/hyperactivity disorder. METHOD: Twenty-four children (mean age
10.9 years, SD = 2.4) participated in a placebo-controlled, double-blind,
crossover trial with 0.15-, 0.30-, and 0.60-mg/kg b.i.d. doses of MPH. Parent
and teacher behavioral ratings, as well as cognitive task performance, were
assessed at each dose. RESULTS: Relative to placebo, most children with
attention-deficit/hyperactivity disorder and mental retardation showed some
degree of behavioral and cognitive improvement with MPH treatment. However,
fewer of these children made substantial gains (>30% improvement, relative to
placebo) with MPH treatment. At the highest dose, 55% of the children showed
substantial behavioral gains and 46% made substantial gains in cognitive task
performance. However, there was substantial independence between changes in
behavior and changes in cognitive performance. CONCLUSIONS: At the 0.60-mg/kg
MPH dose, more children showed substantial cognitive and behavioral gains than
those who showed substantial declines in a ratio of more than 5:1. However, it
may be prudent to assess cognitive change as well as behavioral effects because
improvements in the former do not necessarily forecast improvements in the
latter in children with attention-deficit/hyperactivity disorder and mental
retardation.
-----
J Am Acad Child Adolesc Psychiatry. 2004 Jun;43(6):677-85.
Treatment effects of methylphenidate on cognitive functioning in
children with mental retardation and ADHD.
Pearson DA, Santos CW, Casat CD, Lane DM, Jerger SW, Roache JD, Loveland KA,
Lachar D, Faria LP, Payne CD, Cleveland LA.
Department of Psychiatry and Behavioral Sciences, University of Texas Medical
School at Houston 77030-3497, USA. Deborah.A.Pearson@uth.tmc.edu
OBJECTIVE: Cognitive effects of stimulant medication were investigated in
children with mental retardation (MR) and attention-deficit/hyperactivity
disorder (ADHD). METHOD: Performance on tasks tapping sustained attention,
visual and auditory selective attention, inhibition, and immediate memory was
assessed for 24 children (mean age 10.9 years) during a placebo-controlled,
double-blind, crossover treatment trial with 0.15, 0.30, and 0.60 mg/kg b.i.d.
dosages of methylphenidate (MPH). RESULTS: Successively higher MPH doses were
associated with consistent gains in cognitive task performance, with optimal
performance noted at the highest dose. Analysis of dose-response curves revealed
significant linear components of trend on measures tapping sustained attention,
visual selective attention, auditory selective attention, as well as two tasks
tapping inhibition/impulsivity: delay of gratification and match-to-sample. No
evidence of a curvilinear dose-response relationship emerged for any measure.
CONCLUSIONS: Inattention and disinhibition/impulsivity decline with MPH
treatment in children with ADHD/MR, and consistent with the Multimodal Treatment
Study of ADHD, higher MPH doses are most effective. These findings also suggest
that cognitive testing, together with behavioral and medical assessment, can be
an effective tool in assessing stimulant response in children with ADHD/MR.
-----
Am J Phys Med Rehabil. 2004 Jun;83(6):401-20.
Effects of methylphenidate on attention deficits after traumatic
brain injury: a multidimensional, randomized, controlled trial.
Whyte J, Hart T, Vaccaro M, Grieb-Neff P, Risser A, Polansky M, Coslett HB.
Moss Rehabilitation Research Institute, Albert Einstein Healthcare Network,
Philadelphia, Pennsylvania 19141, USA.
OBJECTIVE: To evaluate the effects of methylphenidate on a variety of aspects of
attention, ranging from laboratory-based impairment measures to caregiver
ratings and work productivity, in individuals after traumatic brain injury.
DESIGN: A total of 34 adults with moderate to severe traumatic brain injury and
attention complaints in the postacute phase of recovery were enrolled in a 6-wk,
double-blind, placebo-controlled, repeated crossover study of methylphenidate,
administered in a dose of 0.3 mg/kg/dose, twice a day. A wide range of
attentional measures was gathered weekly, including computerized and
paper-and-pencil tests of attention, videotaped records of individual work in a
distracting environment, real-time observational scoring of attentiveness in a
classroom environment, and caregiver and clinician rating scales of
attentiveness. Participants also attempted to guess their drug condition each
week. Data from the first ten participants were used for pilot purposes, to
develop attentional factors for composite scoring, and to identify attentional
dimensions suggestive of a treatment effect for independent replication. The
remaining 24 participants' results were used to confirm potential treatment
effects seen in the pilot sample, using Wilcoxon's signed-ranks test on
composite factor scores and individual variables. RESULTS: A total of 54
dependent variables were reduced to 13 composite factors and 13 remaining
individual variables. Of the 13 attentional factors, five showed suggestive
treatment effects in the pilot sample. Of these, three showed statistically
significant treatment effects in the replication sample: speed of information
processing (effect sizes, -0.06 to 0.48; P < 0.001), attentiveness during
individual work tasks (effect sizes, 0.15-0.62; P = 0.01), and caregiver ratings
of attention (effect sizes, 0.44-0.50; P = 0.01). Of the individual variables,
four showed suggestive treatment effects in the pilot sample, but only one
showed significant treatment effects in the replication sample: reaction time
before errors in the Sustained Attention to Response Task (effect size, 0.20; P
= 0.03). No treatment-related improvement was seen in divided attention,
sustained attention, or susceptibility to distraction. None of the variables
showed suggestive or definite negative treatment effects. Effect sizes for those
performance measures positively affected by methylphenidate were in the small to
medium range and included both impairment and activity level measures.
Improvements in processing speed did not seem to come at the expense of
accuracy. CONCLUSIONS: Methylphenidate, at 0.3 mg/kg/dose, given twice a day to
individuals with attentional complaints after traumatic brain injury, seems to
have clinically significant positive effects on speed of processing, caregiver
ratings of attention, and some aspects of on-task behavior in naturalistic
tasks. Further research is needed to identify the optimal dose and to extend
these findings to less carefully selected individuals.
-----
J Am Acad Child Adolesc Psychiatry. 2004 May;43(5):559-67.
Stimulant treatment over five years: adherence, effectiveness,
and adverse effects.
Charach A, Ickowicz A, Schachar R.
Department of Psychiatry, The Hospital for Sick Children and the University of
Toronto, Research Institute, The Hospital for Sick Children, University of
Toronto, Ontario, Canada. alice.charach@sickkids.ca
OBJECTIVE: To evaluate the impact of adherence and medication status on
effectiveness and adverse effects of stimulant use in children with
attention-deficit/hyperactivity disorder (ADHD) over 5 years. METHOD:
Seventy-nine of 91 participants in a 12-month randomized controlled trial of
methylphenidate and parent groups enrolled in a follow-up study. Adherence to
stimulants, treatment response, and adverse effects were evaluated annually for
5 years. Changes in teacher-reported symptoms and parent-reported adverse
effects were compared at 2, 3, 4, and 5 years for 3 groups: adherents,
nonadherents on medication, or nonadherents off medication. Controlling for age,
gender, and baseline severity, adherence status and medication status were
evaluated as correlates of teacher-reported ADHD symptom scores at each year
using multiple regression analyses. RESULTS: At 2 years, adherents (n = 41)
showed greater improvement in teacher-reported symptoms than those off
medication (n = 16) and equivalent response to nonadherents on stimulants (n =
16) (p =.02). At 5 years, adherents (n = 16) showed greater improvement in
teacher-reported symptoms than nonadherents on stimulants (n = 15) and those off
medication (n = 14) (p =.04). At year 2 medication status (beta = 4.67
[0.40-8.95, p =.033]) and at year 5 adherence status (beta = 7.23 [3.01-11.44, p
=.001]) correlated with higher teacher-reported symptom scores. Clinically
significant adverse effects were present for 5 years, most commonly loss of
appetite. CONCLUSIONS: Psychostimulants improve ADHD symptoms for up to 5 years,
but adverse effects persist.
-----
Biol Psychiatry. 2004 May 15;55(10):1031-40.
Modafinil improves cognition and response inhibition in adult
attention-deficit/hyperactivity disorder.
Turner DC, Clark L, Dowson J, Robbins TW, Sahakian BJ.
Department of Psychiatry, University of Cambridge, School of Clinical Medicine,
Cambridge, United Kingdom.
BACKGROUND: Modafinil, a novel cognitive enhancer, has a clinical profile
similar to conventional stimulants such as methylphenidate, despite a seemingly
different mechanism of action. Modafinil selectively improves neuropsychological
task performance in healthy volunteers, possibly through improved inhibitory
control. We examined whether modafinil induced similar improvements in adults
with attention-deficit/hyperactivity disorder. METHODS: Twenty patients with a
DSM-IV diagnosis of attention-deficit/hyperactivity disorder were entered into a
double-blind, randomized, placebo-controlled crossover study using a single 200
mg dose of modafinil. RESULTS: Modafinil produced a similar pattern of cognitive
enhancement to that observed in healthy adults, with improvements on tests of
short-term memory span, visual memory, spatial planning, and stop-signal motor
inhibition. On several measures, increased accuracy was accompanied by slowed
response latency. This alteration in the speed-accuracy trade-off may indicate
that modafinil increases the ability to "reflect" on problems coupled with
decreased impulsive responding. Improvements were also seen in sustained
attention, which was unaffected in healthy subjects. CONCLUSIONS: If these
benefits are shown to be maintained with chronic administration, modafinil may
have potential as an important therapy for attention-deficit/hyperactivity
disorder with a similar effect to stimulants such as methylphenidate in
improving stop-signal response inhibition but without the side effects commonly
experienced with amphetamine-like drugs.
-----
BMC Psychiatry. 2004 Apr 8;4(1):9.
Zinc sulfate as an adjunct to methylphenidate for the treatment
of attention deficit hyperactivity disorder in children: a double blind and
randomized trial.
Akhondzadeh S, Mohammadi MR, Khademi M.
Pychiatric Research Centre, Roozbeh Hospital, Tehran University of Medical
Sciences, South Kargar Street, Tehran 13185, Iran. s.akhond@neda.net
BACKGROUND: Attention-deficit hyperactivity disorder is an early-onset,
clinically heterogenous disorder of inattention, hyperactivity, and
impulsiveness. The diagnosis and treatment of attention-deficit hyperactivity
disorder continues to raise controversy, and, there is also an increase in
treatment options. In this 6-week double blind, placebo controlled-trial, we
assessed the effects of zinc plus methylphenidate in the treatment of children
with attention deficit hyperactivity disorder. To the best of our knowledge,
this study is the first double blind and placebo controlled clinical trial
assessing the adjunctive role of zinc in ADHD. METHODS: Our subjects were 44
outpatient children (26 boys and 18 girls) between the ages of 5-11 (mean +/- SD
was 7.88 +/- 1.67) who clearly met the DSM IV diagnostic criteria for
attention-deficit hyperactivity disorder and they were randomized to
methylphenidate 1 mg/kg/day + zinc sulfate 55 mg/day (with approximately 15 mg
zinc element) (group 1) and methylphenidate 1 mg/kg/day + placebo (sucrose 55
mg) (group 2) for a 6 week double blind clinical trial. The principal measure of
the outcome was the Teacher and Parent ADHD Rating Scale. Patients were assessed
by a child psychiatrist at baseline, 14, 28 and 42 days after the medication
started. RESULTS: The present study shows the Parent and Teacher Rating Scale
scores improved with zinc sulfate over this 6-week, double blind and placebo
controlled trial. The behavior of the two treatments was not homogeneous across
the time. The difference between the two protocols was significant as indicated
by the effect on the group, the between-subjects factor (F = 4.15, d.f. = 1, P =
0.04; F = 4.50, d.f. = 1, P = 0.04 respectively). The difference between the two
groups in the frequency of side effects was not significant. CONCLUSIONS: This
double-blind, placebo-controlled study demonstrated that zinc as a supplementary
medication might be beneficial in the treatment of children with
attention-deficit hyperactivity disorder. However, further investigations and
different doses of zinc are required to replicate these findings in children
with ADHD.
-----
Biol Psychiatry. 2004 Apr 1;55(7):772-5.
Training of slow cortical potentials in
attention-deficit/hyperactivity disorder: evidence for positive behavioral and
neurophysiological effects.
Heinrich H, Gevensleben H, Freisleder FJ, Moll GH, Rothenberger A.
Department of Child and Adolescent Psychiatry, University of Gottingen,
Gottingen, Germany.
BACKGROUND: Learned self-control of slow cortical potentials (SCPs) may lead to
behavioral improvement in attention-deficit/hyperactivity disorder (ADHD).
Hence, training effects should also be reflected at the neurophysiological
level. METHODS: Thirteen children with ADHD, aged 7-13 years, performed 25 SCP
training sessions within 3 weeks. Before and after training, the German ADHD
rating scale was completed by parents, and event-related potentials were
recorded in a cued continuous performance test (CPT). For a waiting-list group
of nine children with ADHD, the same testing was applied. RESULTS: ADHD
symptomatology was reduced by approximately 25% after SCP training. Moreover, a
decrease of impulsivity errors and an increase of the contingent negative
variation were observed in the CPT task. CONCLUSIONS: This study provides first
evidence for both positive behavioral and specific neurophysiological effects of
SCP training in children with ADHD.
-----
Neuropsychobiology. 2004;49(3):130-3.
Tianeptine as a slightly effective therapeutic option for
attention-deficit hyperactivity disorder.
Niederhofer H.
Child and Adolescent Psychiatry, Regional Hospital Bozen, Bolzano, Italy.
helmutniederhofer@yahoo.de
OBJECTIVE: Because of the hypotonic side effect of clonidine, the use of
tianeptine was studied as an alternative because of its longer excretion
half-life, decreased sedative side effects and more selective binding profile.
METHOD: We rated sixty-eight psychiatric outpatients diagnosed with
attention-deficit hyperactivity disorder (ADHD) at baseline and while taking
tianeptine to determine its efficacy as a treatment for ADHD and used
comparisons of Conners' parent ratings within each subject to measure behavioral
changes in the subjects. RESULTS: During tianeptine treatment, patients' mean
scores improved significantly overall, and also for Conners' Hyperactivity,
Inattention and Immaturity factors. CONCLUSIONS: This preliminary study
indicates that tianeptine might be a slightly effective beneficial and useful
treatment for ADHD, reducing hyperactive behaviors and enabling greater
attentional ability with minimal side effects. Copyright 2004 S. Karger AG,
Basel
-----
Curr Opin Pediatr. 2004 Apr;16(2):217-26.
Update on attention-deficit/hyperactivity disorder.
Daley KC.
Department of Medicine, Children's Hospital Boston, Boston, Massachusetts 02115,
USA. katie_daley@vmed.org
PURPOSE OF REVIEW: Attention-deficit/hyperactivity disorder (ADHD) is present in
3% to 10% of children in the United States. Children with ADHD can have academic
impairments, social dysfunction, and poor self-esteem. There is also a higher
risk of both cigarette smoking and substance abuse. Given this, the importance
of treatment for ADHD needs to be underscored. This article will briefly review
the diagnosis, etiology, and treatment of ADHD, with particular focus on
nonstimulant medication and alternative treatment modalities. RECENT FINDINGS:
Recent evidence suggests that the overall rate of medication treatment for ADHD
has been increasing, with over 2 million children being treated with stimulants
in 1997. With this increase, controversy has arisen over the possible
association of stimulants with growth suppression. In addition, estimates
indicate that as many as 30% of children with ADHD either do not respond to
stimulant treatment or cannot tolerate the treatment secondary to side effects.
This has lead to the consideration of treatment with both nonstimulant
medications as well as alternative therapies, including diet, iron
supplementation, herbal medications, and neurofeedback. Considering the various
treatment options now available for ADHD, along with the complexity of the
condition, clinical practice guidelines are emerging for the treatment of ADHD
and will be discussed. SUMMARY: ADHD continues to be a serious health problem.
Adequate treatment is needed to avoid academic impairments, social dysfunction,
and poor self-esteem. This treatment includes consideration of stimulant
medication, nonstimulant medication, as well as alternative therapies. The child
with ADHD is likely better served with a mutimodal treatment plan, including
medication, parent/school counseling, and behavioral therapy. Implementing an
evidenced based algorithm for the treatment of ADHD may prove to be most
effective.
-----
CNS Drugs. 2004;18(4):243-50.
Pharmacokinetic considerations in the treatment of
attention-deficit hyperactivity disorder with methylphenidate.
Wolraich ML, Doffing MA.
University of Oklahoma Health Sciences Center, Child Study Center, Oklahoma
City, Oklahoma 73117, USA. mark-wolraich@ouhsc.edu
Methylphenidate is commonly used for the treatment of attention-deficit
hyperactivity disorder (ADHD). Its efficacy in improving the core symptoms of
ADHD, as well as some of the aggressive and oppositional behaviours, is well
documented, based on a large volume of research. Methylphenidate has a wide
margin of safety and relatively mild adverse effects, most commonly appetite
suppression and insomnia.Methylphenidate is a rapidly absorbed medication that,
in its d-isomer form, readily penetrates the CNS, particularly the striatum. It
appears to function by blocking the reuptake of dopamine.Both the plasma
concentrations and behavioural effects of methylphenidate demonstrate a time to
maximum of between 1 and 3 hours, with the maximum behavioural effects occurring
when the plasma concentrations are increasing. Because of the rapid onset of
action, the effects of methylphenidate can be dramatic but usually last only
about 4 hours with the immediate-release formulation. The behavioural responses
of individuals are also highly variable, so that it is necessary to start
treatment at a low dosage and increase up to a maximally effective dosage
(usually starting at 10-15 mg/day with increases of 10-15mg at weekly intervals
to a maximum dosage of 60 mg/day, irrespective of formulation). Because of the
variability in behavioural responses, assessment of plasma concentrations is not
clinically useful nor does weight help in deciding an appropriate dosage. The
difficulties in administering methylphenidate multiple times a day, particularly
during the school day, have been alleviated in the past few years by the
development of extended-release preparations with varying behavioural effects
lasting 8-12 hours. The 8-hour preparations (Metadate) CD and Ritalin) LA)
utilise a microbead technology, while the 12-hour preparation (Concerta)
utilises an osmotic pump system. All extended-release formulations effectively
control the symptoms of ADHD. While pharmacokinetic differences appear to exist
between some of these new formulations, there are currently no clinical data
available to demonstrate clinical efficacy differences between them.
-----
J Clin Pharm Ther. 2004 Apr;29(2):139-44.
Efficacy of theophylline compared to methylphenidate for the
treatment of attention-deficit hyperactivity disorder in children and
adolescents: a pilot double-blind randomized trial.
Mohammadi MR, Kashani L, Akhondzadeh S, Izadian ES, Ohadinia S.
Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of
Medical Sciences, Tehran, Iran.
Attention-deficit hyperactivity disorder (ADHD) is a common disorder of
childhood that affects 3-6% of school children. Conventional stimulant
medications are recognized as useful symptomatic treatments by both specialists
and parents. Nevertheless, approximately 30% of ADHD children treated with them
do not respond adequately or cannot tolerate the associated adverse effects.
Such difficulties highlight the need for alternative, safe and effective
medications in the treatment of this disorder. Theophylline is a psychomotor
stimulant most widely used as a broncodilator. Purinergic modulation may be
therapeutically beneficial in the treatment of psychiatric disorders. We
hypothesized that theophylline would be beneficial for the treatment of ADHD and
report results of a trial of theophylline compared with methylphenidate for the
treatment of ADHD. A total of 32 children with ADHD as defined by DSM IV were
randomized to theophylline and methylphenidate dosed on an age and
weight-adjusted basis at 4 mg/kg/day (under 12 years) and 3 mg/kg/day
theophylline (over 12 years) (group 1) and 1 mg/kg/day methylphenidate (group 2)
for a 6-week double-blind and randomized clinical trial. The principal measure
of the outcome was the Teacher and Parent ADHD Rating Scale. Patients were
assessed by a child psychiatrist, at baseline and at 14, 28 and 42 days after
start of the medication. No significant differences were observed between
theophylline and methylphenidate on the Parent and Teacher Rating Scale scores
over the trial (t = 0.49, d.f. = 24 P = 0.62 and t = 0.19, d.f. = 24 P = 0.54
respectively). Although the number of dropouts in the methylphenidate group was
higher than the theophylline group, there was no significant difference between
the two protocols in terms of the dropouts. In addition, headaches were observed
more often in the methylphenidate group. The results suggest that theophylline
may be a useful for the treatment of ADHD. In addition, a tolerable side-effect
profile is one of the advantages of theophylline in the treatment of ADHD.
Nevertheless, our study is small and our results would need to be confirmed in a
larger study.
-----
J Clin Psychiatry. 2004;65 Suppl 3:38-45.
Impact of ADHD and its treatment on substance abuse in adults.
Wilens TE.
Department of Psychiatry, Harvard Medical School, Substance Abuse Program in
Pediatric Psychopharmacology, Massachusetts General Hospital, Boston 02114-3117,
USA. twilens@partners.org
Attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance
abuse in adults. Additional psychiatric comorbidity increases this risk. ADHD is
associated with different characteristics of substance abuse: substance abuse
transitions more rapidly to dependence, and lasts longer in adults with ADHD
than those without ADHD. Self-medication may be a factor in the high rate of
substance abuse in adults with ADHD. While previous concerns arose whether
stimulant therapy would increase the ultimate risk for substance abuse, recent
studies have indicated that pharmacologic treatment appears to reduce the risk
of substance abuse in individuals with ADHD. When treating adults with ADHD and
substance abuse, clinicians should assess the relative severity of the substance
abuse, the symptoms of ADHD, and any other comorbid disorders. Generally,
stabilizing or addressing the substance abuse should be the first priority when
treating an adult with substance abuse and ADHD. Treatment for adults with ADHD
and substance abuse should include a combination of addiction
treatment/psychotherapy and pharmacotherapy. The clinician should begin
pharmacotherapy with medications that have little likelihood of diversion or low
liability, such as bupropion and atomoxetine, and, if necessary, progress to the
stimulants. Careful monitoring of patients during treatment is necessary to
ensure compliance with the treatment plan.
-----
J Clin Psychiatry. 2004;65 Suppl 3:27-37.
A guide to the treatment of adults with ADHD.
Weiss MD, Weiss JR.
University of British Columbia Medical Center, Division of Child Psychiatry,
British Columbia's Children's Hospital, Vancouver. mweiss@cw.bc.ca
While child and adolescent physicians are familiar with the treatment of
attention-deficit/hyperac-tivity disorder (ADHD), many adult physicians have had
little experience with the disorder. It is difficult to develop clinical skills
in the management of residual adult manifestations of developmental disorders
without clinical experience with their presentation in childhood. Adult patients
are increasingly seeking treatment for the symptoms of ADHD, and physicians need
practice guidelines. Adult ADHD often presents differently from childhood ADHD.
Because adult ADHD can be comorbid with other disorders and has symptoms similar
to those of other disorders, it is important to understand differential
diagnoses. Physicians should work with patients to provide feedback about their
symptoms, to educate them about ADHD, and to set treatment goals. Treatment for
ADHD in adults should include a medication trial, restructuring of the patient's
environment to make it more compatible with the symptoms of ADHD, and ongoing
supportive management to address any residual impairment and to facilitate
functional and developmental improvements.
-----
J Clin Psychiatry. 2004;65 Suppl 3:22-6.
ADHD treatment across the life cycle.
Spencer TJ.
Department of Pediatric Psychopharmacology, Massachusetts General Hospital,
Department of Psychiatry, Harvard Medical School, Boston 02114, USA.
Since attention-deficit/hyperactivity disorder (ADHD) is usually diagnosed in
children, evidence from the studies of pharmacologic treatments for children
with ADHD is used to inform pharmacologic treatment recommendations for adults.
A large percentage of children diagnosed with ADHD have symptoms that persist
into adolescence and adulthood. Evidence shows that pharmacologic treatments
improve functional outcomes in children with ADHD, and studies using similar
pharmacologic treatments show positive results in adults with ADHD. This article
reviews the use of long-acting methylphenidate, mixed amphetamine salts,
desipramine, monoamine oxidase inhibitors, bupropion, and atomoxetine in studies
of children, adolescents, and adults with ADHD.
-----
J Clin Psychiatry. 2004;65 Suppl 3:18-21.
Diagnosis and treatment of ADHD in adults in primary care.
Montano B.
Department of Family Practice, University of Connecticut Medical School,
Farmington, USA. docmontano@aol.com
The prevalence rate of adult attention-deficit/hyperactivity disorder (ADHD)
indicates that 4.5% of adults continue to exhibit ADHD from childhood. Most
adult sufferers of ADHD have not been properly diagnosed or treated. The
majority of adults with ADHD exhibit at least 1 comorbid psychiatric disorder,
such as major depressive disorder, anxiety disorder, personality disorder,
substance abuse disorder, or bipolar disorder. In many instances, such a
disorder may offer the first clue to diagnosing an adult with ADHD.
Comorbidities may, however, confound a proper ADHD diagnosis, so it is important
to look for and establish an early (childhood) and persistent (lifelong) history
of inattention or hyperactivity. The use of available standardized ADHD rating
scales and checklists will then help the physician to differentiate between ADHD
and other comorbid psychiatric disorders commonly seen in primary care. At
present, there is no universally accepted and efficient standardized assessment
tool for identifying adult ADHD in primary care. However, the Adult Self-Report
Scale Screener may represent such a tool and may be used with ease in a busy
office setting. Using such strategies, primary care providers are still able and
encouraged to identify and treat adults with ADHD.
-----
J Am Acad Child Adolesc Psychiatry. 2004 Apr;43(4):420-9.
A randomized controlled trial of pemoline for
attention-deficit/hyperactivity disorder in substance-abusing adolescents.
Riggs PD, Hall SK, Mikulich-Gilbertson SK, Lohman M, Kayser A.
Department of Psychiatry, University of Colorado School of Medicine, Denver
80262, USA. paula.riggs@uchsc.edu
OBJECTIVE: In adolescents with substance use disorder (SUD), comorbid
attention-deficit/hyperactivity disorder (ADHD) is associated with greater
severity of substance abuse, conduct problems, and worse treatment outcomes.
Although many controlled trials have established the efficacy of
psychostimulants, including pemoline, for ADHD in children and adolescents, none
have been conducted in adolescents with SUD. This randomized, placebo-controlled
trial, conducted between 1996 and 2000, evaluated the safety and efficacy of
pemoline on substance abuse and conduct problems. METHOD: Sixty-nine adolescents
(aged 13-19) with conduct disorder (CD), SUD, and ADHD were recruited from the
community and randomly assigned to a 12-week clinical trial of pemoline (n = 35)
or placebo (n = 34), titrated over 4 weeks to a single morning dose of 75 to
112.5 mg as tolerated. RESULTS: Pemoline had greater efficacy than placebo for
ADHD as determined by significantly more Clinician's Global
Impression-Improvement (CGI-I) ratings of 1 (very much improved) or 2 (much
improved) at the study endpoint (n = 69; p <.05). There was also greater
reduction in ADHD severity on the parent-rated Conners Hyperactivity-Impulsivity
scale in pemoline-treated study completers compared to placebo-treated
completers (pemoline, n = 17; placebo, n = 16; p <.01), but no difference
between groups in the intent-to-treat analysis (n = 68; p <.13). Substance use
did not decline in either group, and there was no difference between groups in
baseline to study endpoint change in substance use or CD symptoms. Overall,
pemoline was well tolerated, demonstrating a good safety profile and no
elevation in liver enzyme levels. CONCLUSIONS: Pemoline was efficacious for ADHD
but did not have an impact on CD or substance abuse in the absence of specific
treatment for SUD.
-----
Expert Opin Drug Saf. 2004 Mar;3(2):93-100.
Evaluation of risks associated with short- and long-term
psychostimulant therapy for treatment of ADHD in children.
Kociancic T, Reed MD, Findling RL.
Department of Psychiatry, University Hospitals of Cleveland, Case Western
Reserve University School of Medicine, Cleveland, OH 44106, USA.
Attention-deficit hyperactivity disorder (ADHD) is a common condition during
childhood that is associated with significant psychosocial dysfunction.
Psychostimulants are the compounds that have been most extensively studied for
the treatment of ADHD in children. There is substantial scientific evidence that
several methylphenidate- and amphetamine-based preparations have acute efficacy
in the treatment of this condition in children. The short-term safety and
tolerability of these compounds has been reasonably well-studied and the risks
associated with psychostimulant therapy in the short-term are generally
acceptable. However, the amount of long-term effectiveness and safety data
relating to these compounds is relatively small. Data that do exist suggest that
long-term treatment with psychostimulants in appropriately diagnosed patients
may be associated with salutary effects as well as relatively modest risks.
Until more extensive, methodologically rigorous data are available, it appears
that judicious psychostimulant pharmacotherapy of ADHD in children may be
justified.
-----
Eur J Clin Nutr. 2004 Mar;58(3):467-73.
Effect of docosahexaenoic acid-containing food administration on
symptoms of attention-deficit/hyperactivity disorder—a placebo-controlled
double-blind study.
Hirayama S, Hamazaki T, Terasawa K.
Department of Early Childhood Education and Care, Kurashiki City College,
Okayama, Japan.
OBJECTIVES: To investigate whether docosahexaenoic acid (DHA) supplementation
was able to ameliorate attention-deficit/hyperactivity disorder(AD/HD) symptoms
in AD/HD children. DESIGN AND SUBJECTS: A placebo-controlled double-blind study
with 40 AD/HD (including eight AD/HD-suspected) children of 6-12 y of age who
were mostly without medication. Subjects of a DHA group (n=20) took active foods
containing fish oil (fermented soybean milk, bread rolls and steamed bread; 3.6
g DHA/week from these foods) for 2 months, whereas those of a control group
(n=20) took indistinguishable control foods without fish oil. The following
items were measured at the start and end of the study: (1) attention deficit,
hyperactivity and impulsivity (AD/HD-related symptoms according to DSM-IV
criteria); (2) aggression assessed by both parents and teachers; (3) visual
perception (finding symbols out of a table); (4) visual and auditory short-term
memory; (5) development of visual-motor integration; (6) continuous performance;
(7) impatience. RESULTS: Changes in tests 1, 2, 3, 5 and 7 over time did not
significantly differ between the two groups. However, visual short-term memory
and errors of commission (continuous performance) significantly improved in the
control group compared with the changes over time in the DHA group (P=0.02 and
0.001, respectively). Recalculation without AD/HD-suspected subjects (n=4 each
group) showed similar P-values with regard to both measures. CONCLUSION: DHA
supplementation did not improve AD/HD-related symptoms. Treatment of ADHD with
fatty acids deserves further investigation, but careful attention should be paid
as to which fatty acid(s) is used.
-----
J Child Health Care. 2004 Mar;8(1):69-81.
ADHD and drug therapy: is it still a valid treatment?
Doggett AM.
School of Education, Colorado State University, USA. doggett@lamar.colostate.edu
The purpose of this article is to discuss alternative treatments other than drug
therapy for Attention-Deficit/Hyperactive Disorder (ADHD) in educational
settings. There is an increasing body of knowledge that supports interventions
for improving cognitive outcomes without the use of medication. The article
explores the risks to ADHD children, shows the potential linkage between gifted
children and ADHD, explores recent brain research, and examines various
alternative treatment options. Information is presented on alternative
treatments such as cognitive behavioral therapies, educational interventions,
electroencephalograph (EEG) neuro-feedback, and diet.
-----
CNS Drugs. 2004;18(6):397-401.
Spotlight on atomoxetine in adults with attention-deficit
hyperactivity disorder.
Simpson D, Plosker GL.
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Atomoxetine (Strattera) is a selective noradrenaline (norepinephrine) reuptake
inhibitor and nonstimulant that has shown greater efficacy than placebo in
attention-deficit hyperactivity disorder (ADHD) in adults. In two large, well
controlled, 10-week trials in adults with ADHD, improvements in ADHD symptoms,
as assessed by investigator- and patient-rated scores, were greater with oral
atomoxetine (60, 90 or 120 mg/day) than with placebo. Mean reductions in the
total ADHD symptom score on the investigator-rated Conners' Adult ADHD Rating
Scale (CAARS) in atomoxetine versus placebo recipients were 28.3% versus 18.1%
and 30.1% versus 19.6%, respectively. Mean reductions in the scores on the
Clinician Global Impression of Severity Scale, patient-rated CAARS and
Wender-Reimherr Adult Attention Deficit Disorder Scale were also significantly
greater with atomoxetine than with placebo. Continued efficacy was demonstrated
in a noncomparative, 34-week extension phase.Atomoxetine was generally well
tolerated in clinical trials; withdrawal rates due to adverse events in
atomoxetine- versus placebo-treated patients participating in the two major
trials were 7.8% versus 4.3% and 9.3% versus 2.4% (p < 0.05 for the latter
trial). Adverse events reported significantly more frequently with atomoxetine
than placebo included dry mouth, insomnia, nausea, decreased appetite,
constipation, dizziness, sweating, dysuria, sexual problems and palpitations.
Modest increases in heart rate and blood pressure were well tolerated and
gradually decreased on cessation of treatment. Atomoxetine was not associated
with QT interval prolongation. Atomoxetine can be administered once or twice
daily. Its subjective-effects profile is different to that of methylphenidate
and atomoxetine is not associated with abuse or diversion; it is therefore not a
controlled substance in the US. This also means repeat prescriptions during
long-term treatment can be more conveniently processed. CONCLUSION: Atomoxetine
is an effective and generally well tolerated treatment for adults with ADHD. It
is a nonstimulant and is the first ADHD treatment to be approved specifically
for adult use based on its efficacy in well controlled adult trials. It can be
administered as a single daily dose or split into two evenly divided doses. It
carries negligible risk of abuse or diversion and is not a controlled substance.
Atomoxetine is a valuable new treatment option for adults with ADHD and is
particularly useful in patients who are at risk for substance abuse or who do
not wish to take a controlled substance.
-----
J Am Acad Child Adolesc Psychiatry. 2004 Mar;43(3):260-8.
Methylphenidate improves visual-spatial memory in children with
attention-deficit/hyperactivity disorder.
Bedard AC, Martinussen R, Ickowicz A, Tannock R.
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
OBJECTIVE: To investigate the effect of methylphenidate (MPH) on visual-spatial
memory, as measured by subtests of the Cambridge Neuropsychological Testing
Automated Battery (CANTAB), in children with attention-deficit/hyperactivity
disorder (ADHD). Visual-spatial memory is a core component of working memory
that has been shown to be impaired in ADHD, irrespective of comorbid reading
and/or language problems. METHOD: A clinic-referred sample of school-age
children with a confirmed DSM-IV diagnosis of ADHD (n = 26) completed tests of
visual-spatial memory, planning ability, and recognition memory in an acute,
randomized, placebo-controlled, crossover trial with three single fixed doses of
MPH. MPH effects on right-handed and left-handed motor control were also
assessed. RESULTS: MPH significantly improved performance on a self-ordered,
updating visual-spatial working memory task and on maintenance of visual-spatial
information but had no effects on measures of visual-spatial planning ability or
recognition memory. Also, MPH significantly improved left-handed motor control.
CONCLUSIONS: Beneficial effects of MPH on visual-spatial processing in ADHD are
selective and restricted to visual-spatial memory.
-----
J Am Acad Child Adolesc Psychiatry. 2004 Mar;43(3):251-9.
A prospective study of stimulant response in preschool children:
insights from ROC analyses.
Short EJ, Manos MJ, Findling RL, Schubel EA.
Department of Psychology, Case Western Reserve University, Cleveland, OH 44106,
USA. EJS3@PO.CWRU.edu
OBJECTIVE: The purpose of this study was to examine the efficacy of
psychostimulant medication in a naturalistic sample of preschoolers. Benefits
and side effects for methylphenidate and mixed amphetamine salts (Adderall) were
examined. METHOD: Twenty-eight preschoolers (ages 4.0 - 5.9) participated in the
present investigation. They were obtained consecutively from a large sample of
suburban children assessed for attention-deficit/hyperactivity disorder. After
having received various dosing levels of a stimulant in a placebo-controlled
crossover design, best dose was assigned based on the lowest Abbreviated
Symptoms Questionnaire T score received in a given week. All analyses compared
best dose ratings to placebo ratings. RESULTS: Preschoolers' behavioral ratings
by parents and teachers were improved as a function of stimulant medication.
More than 82% of the medicated sample improved their behavioral rating by at
least 1 SD as demonstrated by receiver operating characteristic (ROC) analyses,
with more than 50% of medicated preschoolers improving by more than 2 SD. Side
effects were infrequent at best dose of medication. CONCLUSIONS: Clinically
significant changes in behavioral ratings of preschoolers were noted in response
to stimulant medication. Both stimulants were well tolerated. ROC curves were
useful for clearly depicting on a case-by-case basis how much improvement was
derived from psychopharmacological treatment.
-----
Int Clin Psychopharmacol. 2004 Jan;19(1):17-22.
Treatment modalities among US children diagnosed with
attention-deficit hyperactivity disorder: 1995-99.
Robison LM, Sclar DA, Skaer TL, Galin RS.
Pharmacoeconomics and Pharmacoepidemiology Research Unit, College of Pharmacy,
Washington State University, Pullman 99164-6510, USA. lrobison@wsu.edu
The objective of this study was to determine the prevalence of single and
combination treatment modalities among US children aged 5-18 years who were
diagnosed with attention-deficit hyperactivity disorder (ADHD). Treatments
included: (i) stimulant pharmacotherapy alone; (ii) psychotherapy and/or mental
health counselling alone; (ii) a combination; or (iv) no treatment. Data from
the US National Ambulatory Medical Care Survey (NAMCS) for the years 1995-99,
were used for this analysis. Office-based physician-patient visits documenting a
recorded diagnosis of ADHD (ICD-9-CM codes 314.00 or 314.01) were extracted from
the NAMCS. Findings are presented for children diagnosed with ADHD with or
without comorbid mental illness, for children diagnosed with ADHD without
comorbid mental illness, by gender, and by age groups. Over the timeframe
1995-99, an estimated 14 402 090 office-based visits documented a diagnosis of
ADHD, with (24%) or without (76%) comorbid mental illness, among children aged
5-18 years. Overall, the most frequent treatment was stimulant medication alone
(42.0%). This was followed by the combination treatment of stimulant medication
plus psychotherapy and/or mental health counselling (32.1%). Only 10.8% of the
children received psychotherapy and/or mental health counselling alone; 15.1%
received no treatment beyond the office-based visit. This pattern was consistent
for boys and girls; however, a larger proportion of boys (11.7%) were receiving
psychotherapy and/or mental health counselling alone than girls (8.2%). More
girls (18.7%) were receiving no treatment option compared to boys (13.9%). The
percentage of children receiving psychotherapy and/or mental health counselling
alone increased with each age group (6.7%, 5-8 years; 11.3%, 9-12 years; 13.6%,
13-18 years), as did the combination treatment of stimulant medication plus
psychotherapy and/or mental health counselling (28.2%, 31%, 37.3%,
respectively). Only 8.2% of children age 13-18 years were receiving no treatment
option compared to 16.9% of children age 9-12 years, and 19.5% of those aged 5-8
years. The reasons for the gender and age group differences discerned in this
study require further investigation, as does the reason why 15.1% of children
were receiving no treatment beyond the office-based visit.
-----
Exp Clin Psychopharmacol. 2004 Feb;12(1):57-64.
Effect of methylphenidate on time perception in
children with attention-deficit/hyperactivity disorder.
Baldwin RL, Chelonis JJ, Flake RA, Edwards MC, Feild CR,
Meaux JB, Paule MG.
Department of Pediatrics, University of Arkansas for Medical Sciences--Arkansas
Children's Hospital, Little Rock, AR 72202, USA. baldwinronaldL@uams.edu
The effects of methylphenidate (MPH) on performance of a time-production
task were studied in 17 children with attention-deficit/hyperactivity
disorder who participated in 1 test session on and 1 off MPH.
Participants held a response lever down for at least 10 but no
longer than 14 s. Administration of MPH had no effect on the number
of correct responses or on the mean duration of lever holds. MPH
administration significantly decreased timing response variability,
increased holds of 10- to 11-s duration, and decreased lever holds
of extremely short durations. These results indicate that administration
of MPH resulted in more precise timing performance without changing
the mean duration of lever holds, suggesting an enhancement in
working memory.
-----
Ann Pharmacother. 2004 Jan;38(1):86-90.
Atomoxetine treatment of attention-deficit/hyperactivity
disorder.
Eiland LS, Guest AL.
Harrison School of Pharmacy, Auburn University, Huntsville, AL
35801, USA. eilanls@auburn.edu
OBJECTIVE: To review the literature of the first nonstimulant
approved for treatment of attention-deficit/hyperactivity disorder
(ADHD). DATA SOURCES: Primary literature and review articles were
obtained through PubMed/MEDLINE (1966-February 2003). STUDY SELECTION
AND DATA EXTRACTION: Literature evaluating atomoxetine in ADHD
was selected. Animal data were excluded. DATA SYNTHESIS: Stimulants
are currently first-line therapy for ADHD. However, their use
raises several concerns including the potential for abuse and
adverse effects. Atomoxetine introduces a new therapeutic drug
class, selective norepinephrine-reuptake inhibitors, for ADHD
management. This additional treatment option offers potential
advantages over current therapies. CONCLUSIONS: Clinical trials
demonstrate that atomoxetine is a safe and effective alternative
for ADHD treatment in children and adults; however, its disadvantages
may hinder it from becoming a first-line agent.
-----
No To Hattatsu. 2004 Jan;36(1):31-6.
[Memory functions in children with attention deficit/hyperactivity
disorder—the effects of methylphenidate on them]
[Article in Japanese]
Kitazawa S, Hirabayashi S, Kobayashi M.
Departments of Rehabilitation (SK, MK) and Child Neurology (SH),
Nagano Children's Hospital, Minamiazumi, Nagano. sanae_kitazawa@hospital.nagano.nagano.jp
The memory functions or capacities in attention-deficit/hyperactivity
disorder (AD/HD) are still not clear, though it has been pointed
that the working memory in AD/HD could be impaired due to difficulties
of motor inhibition or self-regulation. We examined the Auditory
Verbal Learning Test (AVLT) and the Rey-Osterrieth Complex Figure
Test (RCFT) in addition to the memory tasks of ordinary intelligence
tests (WISC-III and K-ABC) in children with AD/HD. Whether these
results could be improved by methylphenidate administration or
not was also evaluated. Over the half cases had normal results
without medication. Some cases in whom methylphenidate were clinically
effective showed improved memory functions, especially in the
auditory long-term memory, after methylphenidate administration.
In conclusion, memory capacities seem normal in AD/HD. Methylphenidate
does not have an effect on the memory capacities, but may improve
the strategies in which the short-term memory can be effectively
transferred to the long-term memory.
-----
Issues Emerg Health Technol. 2003 May;(46):1-4.
Atomoxetine for attention deficit/hyperactivity
disorder.
Garces K.
Seven randomized, double-blinded, controlled trials in children,
adolescents and adults have shown that atomoxetine improves attention
deficit/hyperactivity disorder (ADHD) symptoms compared to placebo.
There is no evidence that atomoxetine has greater efficacy or
a better safety profile than currently used therapy. Atomoxetine
has been submitted for regulatory approval in Canada and is currently
approved in the US. The price of atomoxetine in Canada has not
been established.
-----
CNS Spectr. 2003 Apr;8(4):253-8.
Non-stimulant treatment of attention-deficit/hyperactivity
disorder.
Pliszka SR.
Department of Psychiatry, University of Texas Health Science Center,
San Antonio 78284, USA. pliszka@uthscsa.edu
Stimulants are a highly efficacious and safe treatment for
attention-deficit/hyperactivity disorder (ADHD), with 75% to 90%
of patients responding well if two different stimulants (amphetamine
and methylphenidate) are used. Nonetheless, a subset of ADHD patients
will either fail to respond to stimulants or have side effects
that preclude their use (tics, severe loss of appetite, marked
insomnia). For such patients, there are a number of non-stimulant
agents that serve as second-line treatments. Tricyclic antidepressants
(TCAs) are the most studied of these drugs. They are superior
to placebo in the treatment of ADHD and may reduce abnormal movements
in patients with ADHD/tic disorder. TCAs often produce side effects
of sedation, dry mouth, and constipation. Bupropion is superior
to placebo in the treatment of ADHD and has a more favorable side-effect
profile than the TCAs. A new selective norepinephrine reuptake
inhibitor, atomoxetine, has been shown to be efficacious in the
treatment of ADHD and has recently received an approvable letter
from the Food and Drug Administration. The a-agonists clonidine
and guanfacine have also been used as alternative agents in ADHD,
though the controlled data are more limited. A recent controlled
clinical trial suggests a combination of methylphenidate and clonidine
has advantages in the treatment of comorbid ADHD and tics over
either medication alone. Clinical guidelines for each of these
agents, as well as their use in combination with stimulants in
comorbid conditions, will be discussed.
-----
J Am Acad Child Adolesc Psychiatry. 2003 Apr;42(4):424-33.
ADHD treatment with once-daily OROS methylphenidate:
interim 12-month results from a long-term open-label study.
Wilens T, Pelham W, Stein M, Conners CK, Abikoff H, Atkins M,
August G, Greenhill L, McBurnett K, Palumbo D, Swanson J, Wolraich
M.
Clinical Research Program in Pediatric Psychopharmacology, Massachusetts
General Hospital and Harvard Medical School, 15 Parkman Street,
Boston, MA 02114, USA. wilens@helix.mgh.harvard.edu.
OBJECTIVE: Few treatment studies of attention-deficit/hyperactivity
disorder (ADHD) extend beyond a few months. This article reports
an interim analysis of a 24-month study evaluating the 12-month
tolerability and effectiveness of a once-daily OROS formulation
of methylphenidate (OROS MPH) in children with ADHD. METHOD: Children,
aged 6-13 years, with ADHD who participated in previous controlled
studies and were MPH responders, received once-daily OROS MPH
in this multicenter, open-label, nonrandomized study. Effectiveness
was evaluated monthly by parents/caregivers and schoolteachers
using validated rating scales (e.g., IOWA Conners). Safety and
adverse events assessments involved objective (e.g., vital signs,
growth) and subjective (sleep quality, tics) reporting. RESULTS:
Seventy-one percent of subjects (289/407) completed 12 months'
treatment. Effectiveness was maintained throughout 12 months as
demonstrated by stable IOWA Conners ratings and sustained improvements
in peer interaction and Global Assessment Scale scores. OROS MPH
was well tolerated, with adverse events similar to those expected
with short-acting stimulant medication. OROS MPH had minimal impact
on sleep quality and tics. There were no clinically meaningful
changes in blood pressure, pulse, or height. The apparent absence
of meaningful changes is tempered by the fact that children were
MPH responders and were medicated at baseline, most for extended
periods prior to enrollment. CONCLUSION: In this open-label study,
once-daily OROS MPH treatment appears to be well tolerated and
effectiveness was maintained for up to 12 months in these children
with ADHD.
-----
CMAJ. 2003 Mar 18;168(6):715-22.
Assessment and management of attention-deficit
hyperactivity disorder in adults.
Weiss M, Murray C.
Division of Child Psychiatry, University of British Columbia,
Vancouver, BC. mweiss@cw.bc.ca
Attention-deficit hyperactivity disorder (ADHD) is estimated
to affect 2%-6% of adults. The symptoms in adults with ADHD mirror
those in children with the disorder and are associated with significant
educational, occupational and interpersonal difficulties. Double-blind,
placebo-controlled trials have established that adult ADHD is
responsive to stimulant medication treatment. New medications
and psychotherapeutic approaches are being developed in an effort
to achieve optimal treatment effects in this population. We review
the available literature and provide an approach to the assessment
and management of ADHD in adults.
-----
J Child Psychol Psychiatry. 2003 Feb;44(2):159-68.
Annotation: The use of psychotropic medications
in children: an American view.
Wolraich ML.
Oklahoma University Health Sciences Center, USA. mark-wolraich@ouhsc.edu
BACKGROUND: Psychotropic medications have become an integral
component in the treatment of children with mental illnesses.
METHODS: Selective reviews of the empirical evidence for the efficacy
of psychotropic medications and studies of their use patterns
were reviewed. RESULTS: Very strong efficacy for at least the
short-term benefits and safety of stimulant medications was found
and some good efficacy and safety evidence for the treatment of
anxiety and depressive disorders with seratonin reuptake inhibitors
(SSRI) was also found. Efficacy for tricyclic antidepressants
to treat attention deficit hyperactivity disorder was found but
the presence of significant side effects makes them less the drugs
of choice. Other medications are presented but with less rigorous
evidence. Studies of use found that stimulant medications are
extensively prescribed in the US by both psychiatrists and primary
care physicians. SSRI are also prescribed extensively but not
to the extent of stimulants and are more frequently prescribed
by psychiatrists. CONCLUSIONS: There is now good evidence for
the efficacy of some psychotropic agents and their use is an integral
component in the management of childhood mental illnesses.
-----
Pharmacotherapy. 2003 Feb;23(2):222-30.
A survey of herbal use in children with attention-deficit-hyperactivity
disorder or depression.
Cala S, Crismon ML, Baumgartner J.
Kaiser Permanente, Denver, Colorado, USA.
OBJECTIVE: To examine whether herbal medicines were given to
children or adolescents receiving care for attention-deficit-hyperactivity
disorder or depression. METHODS: Between October 2000 and July
2001, a 23-item questionnaire was administered in five community
mental health centers in Texas. Parents or primary caregivers
of children who received a psychiatric assessment were sought
for participation. One hundred seventeen caregivers completed
a questionnaire. The main outcome measure was primary caregivers'
self-report of the use of herbal therapy in their children. RESULTS:
The lifetime prevalence of herbal therapy in patients was 20%
(23 patients). Eighteen patients (15%) had taken herbal medicines
during the past year. Recommendations from a friend or relative
resulted in the administration of herbal medicines by 61% of 23
caregivers. Herbal medicines were given most frequently for a
behavioral condition, with ginkgo biloba, echinacea, and St. John's
wort most prevalent. Almost 83% of caregivers gave herbal medicines
alone, whereas 13% gave herbal medicines with prescription drugs.
Most caregivers (78%) supervised the administration of herbal
therapy in their children; the children's psychiatrists (70%),
pediatricians (56%), or pharmacists (74%) typically were not aware
of the use. CONCLUSIONS: Most caregivers supervised herbal therapy
in their children, without communication with a health professional.
A need exists for better communication between health professionals
and caregivers regarding the use of herbal therapy.
-----
Arch Gen Psychiatry. 2003 Feb;60(2):204-11.
Development of a new once-a-day formulation of
methylphenidate for the treatment of attention-deficit/hyperactivity
disorder: proof-of-concept and proof-of-product studies.
Swanson J, Gupta S, Lam A, Shoulson I, Lerner M, Modi N, Lindemulder
E, Wigal S.
University of California, Irvine, Department of Pediatrics, Child
Development Center, CA, USA.
BACKGROUND: The duration of action of the immediate-release
formulation of methylphenidate hydrochloride is short (3 to 4
hours), and 3 times daily dosing is thought to maximize effectiveness
across a 12-hour day. The initial sustained-release formulations
of methylphenidate had reduced efficacy compared with immediate-release
methylphenidate and were not well accepted. Tachyphylaxis was
hypothesized to account for the reduced effects, and an ascending
drug delivery pattern was proposed to overcome this acute tolerance.
METHODS: Children with attention-deficit/hyperactivity disorder
were evaluated in a laboratory school to characterize onset and
duration of the effect of a variety of methylphenidate regimens.
In a proof-of-concept study, an experimental ascending profile
was established by an initial bolus followed by small increasing
doses of immediate-release methylphenidate in capsules administered
every 30 minutes for 8 hours. Two proof-of-product studies of
a new oral once-a-day formulation to deliver methylphenidate by
an osmotic pump process based on OROS (ALZA Corp, Mountain View,
Calif) technology (hereafter referred to "OROS-methylphenidate")
were conducted: a pharmacokinetic study and a pharmacodynamic
study. RESULTS: The experimental ascending profile matched the
effect of the standard regimen of methylphenidate, 3 times daily.
In the pharmacokinetic study, OROS-methylphenidate treatment produced
a rapid rise followed by increasing plasma concentrations that
peaked 7 to 9 hours after administration. In the pharmacodynamic
study, OROS-methylphenidate treatment matched the 3 times daily
dosing of methylphenidate for onset and duration of efficacy.
CONCLUSIONS: These studies demonstrate the translation of a basic
science finding (acute tolerance to clinical doses of methylphenidate)
into clinical application (the selection of a new drug delivery
pattern for methylphenidate). This approach produced a new product
(OROS-methylphenidate or Concerta), which proved to have the predicted
rapid onset (with 1-2 hours) and long duration of efficacy (10-12
hours) after a single administration in the morning.
-----
J Child Neurol. 2003 Feb;18(2):109-12.
Use of methylphenidate for attention-deficit hyperactivity
disorder in patients with epilepsy or electroencephalographic
abnormalities.
Gucuyener K, Erdemoglu AK, Senol S, Serdaroglu A, Soysal S, Kockar
AI.
Department of Pediatric Neurology, Faculty of Medicine, Gazi University,
Ankara, Turkey.
Methylphenidate is commonly believed to lower seizure threshold.
The safe use of methylphenidate has not been clarified in patients
with attention-deficit hyperactivity disorder (ADHD) and concomitant
active seizure or electroencephalographic (EEG) abnormalities.
Patients with ADHD and active seizures (n = 57) and patients with
ADHD and EEG abnormalities (n = 62), 6 to 16 years of age, were
included in the study. The safety and efficacy of treatment with
antiepilepsy drugs combined with methylphenidate were determined
by assessing seizure frequency, changes in ADHD symptoms, the
Conners' Rating Scales, EEG differences, and side effects. The
Conners' Rating Scales, performed by parents and teachers, and
mean total ADHD symptom scores at the beginning of the study and
at the end were significantly different (P = .05 for the Conners'
Rating Scales and P = .001 for ADHD symptom scores). Methylphenidate
had a beneficial effect on EEG. Seizure frequency did not change
from baseline. The side effects of methylphenidate were mild and
transient Methylphenidate is safe and effective in children with
ADHD and concomitant active seizures or EEG abnormalities.
-----
Biol Psychiatry. 2003 Jan 15;53(2):112-20.
Atomoxetine in adults with ADHD: two randomized,
placebo-controlled studies.
Michelson D, Adler L, Spencer T, Reimherr FW, West SA, Allen AJ,
Kelsey D, Wernicke J, Dietrich A, Milton D.
Lilly Research Laboratories, Indianapolis, Indiana 46285, USA.
BACKGRAUND: Attention-deficit/hyperactivity disorder (ADHD)
has been less studied in adults than in children, and the treatment
studies reported to date have been small, single-center trials.
To assess the efficacy of atomoxetine, a new and highly selective
inhibitor of the norepinephrine transporter, we conducted two
large, multicenter treatment trials. METHODS: Two identical studies
using randomized, double-blind, placebo-controlled designs and
a 10-week treatment period were conducted in adults with DSM-IV-defined
ADHD as assessed by clinical history and confirmed by a structured
interview (study I, n = 280; study II, n = 256). The primary outcome
measure was a comparison of atomoxetine and placebo using repeated
measures mixed model analysis of postbaseline values of the Conners'
Adult ADHD Rating Scale. RESULTS: In each study, atomoxetine was
statistically superior to placebo in reducing both inattentive
and hyperactive and impulsive symptoms as assessed by primary
and secondary measures. Discontinuations for adverse events among
atomoxetine patients were under 10% in both studies. CONCLUSION:
Atomoxetine appears to be an efficacious treatment for adult ADHD.
Its lack of abuse potential may be an advantage for many patients.
-----
Curr Drug Target CNS Neurol Disord. 2002 Aug;1(4):423-31.
Nicotinic treatment for cognitive dysfunction.
Levin ED, Rezvani AH.
Department of Psychiatry and Behavioral Sciences, Duke University
Medical Center, Durham, NC 27710, USA. edlevin@duke.edu
Nicotinic medications may provide beneficial therapeutic treatment
for cognitive dysfunction such as Alzheimer's disease, schizophrenia
and attention deficit hyperactivity disorder (ADHD). For development
of nicotinic treatments we are fortunate to have a well characterized
lead compound, nicotine. Transdermal nicotine patches offer a
way to deliver measured doses of nicotine in a considerably safer
fashion than the more traditional means of administration, tobacco
smoking. We have found that transdermal nicotine significantly
improves attentional function in people with Alzheimer's disease,
schizophrenia or ADHD as well as normal nonsmoking adults. To
follow-up on this proof of principal that nicotinic treatment
of cognitive dysfunction holds promise, it is important to use
animal models to determine the critical neurobehavioral bases
for nicotinic involvement in cognitive function so that more selective
nicotinic analogues that improve cognitive function with fewer
side effects can be developed. We have found with local infusion
in rat studies that the hippocampus and amygdala are important
substrates for nicotinic effects on working memory function. Both
alpha7 and alpha4beta2 nicotinic receptors are involved in working
memory. Nicotinic interactions with dopaminergic and glutaminergic
systems are also important in the basis of cognitive function.
Studies of the neural nicotinic mechanisms underlying cognitive
function are key for opening avenues for development of safe and
effective nicotinic treatments for cognitive dysfunction.
-----
J Atten Disord. 2002;6 Suppl 1:S109-19.
Non-stimulant treatment for Attention-Deficit/Hyperactivity
Disorder.
Spencer T, Biederman J.
Pediatric Psychopharmacology Unit, Psychiatry Service at Massachusetts
General Hospital, Boston 02114, USA.
A variety of compounds with a common noradrenergic/dopaminergic
activity have shown documented anti-Attention-Deficit/Hyperactivity
Disorder (ADHD) activity. There is a substantial body of literature
documenting the efficacy of tricyclic antidepressants on ADHD
in over 1,000 subjects. There is an equally large database on
the efficacy of the specific norepinephrlne reuptake inhibitor,
atomoxetine, of greater than 2,000 Individuals. In addition, the
atypical antidepressant buproplon also has been documented to
be effective in the treatment of ADHD in controlled clinical trials.
Despite wide use, the scientific base supporting the efficacy
of alpha-2, noradrenergic agonists is somewhat limited. Several
lines of evidence provide preliminary support for the potential
benefits of cholinergic cognitive enhandng drugs, such as anticholinesterase
inhibitors (tacrine, donepezil) as well as novel nicotinic analogues
(ABT-418). Despite these promising results, more research is needed
on alternative pharmacological treatments for the treatment of
ADHD.
-----
Rev Prat. 2002 Nov 15;52(18):2013-6.
[Psychotherapy in children with attention deficit
hyperactivity disorder]
[Article in French]
George G.
Policlinique Ney 124, boulevard Ney 75018 Paris. gisele.george@libertysurf.fr
Alone or used with psychostimulants, psychotherapy is the keystone
of the treatment in children attention deficit disorder hyperactivity
(ADHD). This article explains in which matter psychotherapy is
essential. To be well done, it's necessary before starting the
treatment to analyze precisely the disorder and how it interferes
with the child's environment. It describes how this functional
analysis must be done in order to be more precise in the choice
of the treatment objectives. This article explains why in children
ADHD treatment, the individual therapy must be associated with
a family training and describes briefly the more studied and recognized
psychotherapy techniques in those children ADHD and how other
partners (teacher, speech or motor therapist) are also useful.
-----
Rev Prat. 2002 Nov 15;52(18):2009-12.
[Outcome of hyperactive children]
[Article in French]
Messerschmitt P.
Unite de psychopathologie de l'enfant et de l'adolescent Hopital
Armand-Trousseau 75571 Paris. paul.messerschmitt@trs.ap-hop-paris.fr
Two issues are examined: 1. Does comorbidity in ADHD interfere
with the longitudinal outcome? 2. Is adult ADHD a clinical reality.
It seems that marked impairment in ADHD children social functioning
(conduct disorders, aggressivity, destructive behavior) is a significant
predictor of adult social disability (substance use disorders,
antisocial personality and even criminality). Adult ADHD seems
to be a reality, but much less frequent than in youths. Impulsivity,
attention disorder, and emotional status are the main characters
of the syndrome. We have no data leading to the responsibility
of psychostimulant treatment in substance use disorders in teenage
or adulthood. Implications of early versus late onset of ADHD
symptoms are not clear. Early onset (before 7) seems to be associated
with worse clinical outcomes.
-----
J Atten Disord. 2002;6 Suppl 1:S101-7.
Methylphenidate in treatment of adults with Attention-Deficit/Hyperactivity
Disorder.
Biederman J, Spencer T.
Pediatric Psychopharmacology Unit, Child Psychiatry Service, Massachusetts
General Hospital, Boston 02114, USA.
Attention-Deficit/Hyperactivity Disorder (ADHD) can persist
into adulthood with a continuation of the pattern of childhood
psychopathology, cognition and functioning. Adult comorbidities
include substance use disorders, antisocial personality disorder,
anxiety, and depression. Studies have shown that as in children,
methylphenidate treatment for adults can lead to a robust, dose-dependent
improvement in ADHD symptoms. Future research is needed to evaluate
the safety and efficacy of long-term treatment with methylphenidate
(MPH).
-----
J Atten Disord. 2002;6 Suppl 1:S89-100.
Guidelines and algorithms for the use of methylphenidate
in children with Attention-Deficit/
Hyperactivity Disorder.
Greenhill L, Beyer DH, Finkleson J, Shaffer D, Biederman J, Conners
CK, Gillberg C, Huss M, Jensen P, Kennedy JL, Klein R, Rapoport
J, Sagvolden T, Spencer T, Swanson JM, Volkow N.
New York State Psychiatric Institute/Columbia University, New
York 10032, USA. LarryLGreenhill@cs.com
OBJECTIVE: To review published algorithms for guiding the use
of methylphenidate (MPH) in the treatment of Attention-Deficit/Hyperactivity
Disorder (ADHD) in children and adolescents. METHODS: A consensus
roundtable of 12 experts was convened to review the evidence for
the safety and efficacy of MPH in the treatment of ADHD, as well
as the published algorithms and practice guidelines for using
MPH. The experts reviewed the algorithms for practicality and
acceptability by clinicians. RESULTS: Algorithms that included
MPH commonly selected it as the initial medication to be employed
in the treatment of children with ADHD. Factors involved included
its high efficacy, good safety record, and the ubiquitous nature
of its appearance in the ADHD treatment literature. CONCLUSIONS:
MPH should be considered as the first medication to be used in
a treatment algorithm for children and adolescents with ADHD.
-----
J Atten Disord. 2002;6 Suppl 1:S45-56.
Longer term effects of stimulant treatments for
Attention-Deficit/Hyperactivity Disorder.
Jensen P.
Center for the Advancement of Children's Mental Health, Columbia
University, New York, NY 10032, USA. pj131@columbia.edu
Of pharmacological options available for Attention-Deficit/Hyperactivity
Disorder (ADHD), stimulant medications are the most studied, the
most commonly used, the most effective, and the first-line choice
for treatment. Evidence of the short-term efficacy of methylphenidate
(MPH) and other stimulants as well as behavioral treatments in
the management of symptoms of ADHD is abundant This paper reviews
therapeutic trials with a duration or follow-up period of 12 months
or more and evaluates the longer term outcomes of available treatments
for ADHD. The trials were reported by Ialongo et al. (1993), Horn
et al. (1991), Schachar, Tannock, Cunningham, and Corkum (1997),
Gillberg et al. (1997), Hechtman and Abikoff (1995), and the National
Institute of Mental Health (MTA Cooperative Group, 1999a, 1999b).
-----
J Atten Disord. 2002;6 Suppl 1:S17-30.
Forty years of methylphenidate treatment in Attention-Deficit/
Hyperactivity Disorder.
Conners CK.
Duke University Medical Center ADHD Program, Durham, NC 27705,
USA. ckconners1@direcway.com
This paper reviews approximately 40 years of stimulant drug
treatment of children with behavior and learning problems. These
patients generally fall under the rubric of Attention-Deficit/Hyperactivity
Disorder (ADHD), with core symptoms of hyperactivity, impulsivity,
and inattention being the most studied and most robust of the
targets for stimulant treatment. In addition, the drug effects
on other targets, such as cognitive and academic function, are
included. The largest selection of studies involves methylphenidate.
Both qualitative studies and meta-analytic studies from major
reviews are examined. Variations in the methodology of the reviews
are described and some of the discrepancies in interpretation
examined. Despite wide variations in subject selection, types
of trials, degree of methodological rigor, and the decade in which
the studies took place, the evidence is remarkably consistent
The overall results suggest significant clinical impact upon the
core features of ADHD. More studies of long-term effects and special
populations such as older adolescents and adults will be necessary,
though existing evidence strongly supports similar findings as
for the younger patients with a diagnosis of ADHD.
-----
J Clin Psychiatry. 2002;63 Suppl 12:50-5.
Safety profile of atomoxetine in the treatment
of children and adolescents with ADHD.
Wernicke JF, Kratochvil CJ.
Eli Lilly and Company, Lilly Corporate Center DC-6026, Indianapolis,
IN 46285, USA.
Atomoxetine is a selective norepinephrine reuptake inhibitor
that is being developed for the treatment of attention-deficit/hyperactivity
disorder (ADHD). Atomoxetine will be the first nonstimulant medication
approved by the U.S. Food and Drug Administration (FDA) for the
treatment of ADHD. Throughout the testing phases, more than 2000
children and adolescents have been exposed to atomoxetine in clinical
trials, with both the number of exposures and the length of exposure
time increasing. Serious adverse events have not been clearly
associated with the drug, and there have been few discontinuations
due to adverse events. The most common drug-related event reported
in trials has been decreased appetite and an initial period of
weight loss followed by an apparently normal rate of weight gain.
These events tend to appear early in the course of treatment with
atomoxetine and then decline. Atomoxetine has also been associated
with mild increases in blood pressure and pulse that plateau during
treatment and resolve upon discontinuation. There have been no
effects seen on the QT interval, and the cytochrome P450 2D6 metabolism
of patients seems to have little effect on safety or tolerability
of the drug. This article will review the data from completed
and ongoing clinical trials available at the time the New Drug
Application was submitted to the FDA. Described are serious adverse
events, discontinuations, and treatment-emergent adverse events.
Specifically, cardiac effects and effects on weight, height, and
metabolism that are related to treatment of ADHD with atomoxetine
in children and adolescents are discussed.
-----
J Clin Psychiatry. 2002;63 Suppl 12:36-43.
Psychosocial treatments for attention-deficit/hyperactivity
disorder in children.
Barkley RA.
Department of Psychiatry, University of Massachusetts Medical
School, Worcester, 55 Lake Ave. N., Worcester, MA 01655, USA.
barkleyr@ummhc.org
This article provides a brief overview of the major psychosocial
treatments that have some efficacy for the management of attention-deficit/hyperactivity
disorder (ADHD) in children. Parent training in effective child
behavior management methods, classroom behavior modification methods
and academic interventions, and special educational placement
appear to have the greatest promise of efficacy. Augmenting these,
additional family therapy in problem-solving and communication
skills and the coordination of multiple school resources across
the day may be necessary. To be effective in improving prognosis,
treatments must be maintained over extended periods of time.
-----
J Clin Psychiatry. 2002 Dec;63(12):1140-7.
Results from 2 proof-of-concept, placebo-controlled
studies of atomoxetine in children with attention-deficit/hyperactivity
disorder.
Spencer T, Heiligenstein JH, Biederman J, Faries DE, Kratochvil
CJ, Conners CK, Potter WZ.
Massachusetts General Hospital, Boston, USA.
BACKGROUND: Atomoxetine is a nonstimulant drug being studied
for the treatment of attention-deficit/hyperactivity disorder
(ADHD). Atomoxetine is a highly specific inhibitor of the presynaptic
norepinephrine transporter with minimal affinity for other noradrenergic
receptors or other neurotransmitter transporters or receptors.
Results of 2 proof-of-concept studies are reported that tested
the hypothesis that a selective inhibitor of presynaptic norepinephrine
uptake would be effective for the treatment of ADHD in school-aged
children. METHOD: Two identical 12-week, stratified, randomized,
double-blind, placebo-controlled trials were conducted in children
who met DSM-IV criteria for ADHD. The primary efficacy outcome
measure was the mean change from baseline to endpoint in the Attention-Deficit/Hyperactivity
Disorder Rating Scale (ADHD RS) total score. Secondary efficacy
measures included the Clinical Global Impressions-ADHD-Severity
(CGI-ADHD-S) and the Conners' Parent Rating Scale-Revised: Short
Form (CPRS-R:S). RESULTS: A total of 291 patients were randomized
in the 2 trials combined (Study 1, N = 147; Study 2, N = 144).
Stimulant-naive patients were randomized to atomoxetine, placebo,
or methylphenidate. Patients with prior stimulant exposure were
randomized to atomoxetine or placebo. Atomoxetine significantly
reduced ADHD RS total scores compared with placebo in each study
(p <.001). Changes in the CGI-ADHD-S (Study 1: p =.003; Study
2: p =.001) and CPRS-ADHD Index (Study 1: p =.023; Study 2: p
<.001) also showed atomoxetine to be statistically significantly
superior to placebo in reducing ADHD symptoms. Atomoxetine was
found to be well tolerated in this population of pediatric patients.
CONCLUSION: Two studies of atomoxetine early in its development
confirmed that atomoxetine, a specific and selective inhibitor
of noradrenergic uptake, was effective for the treatment of children
with ADHD. In addition, atomoxetine was found to be well tolerated.
-----
Exp Clin Psychopharmacol. 2002 Nov;10(4):400-7.
Stimulant medication improves recognition memory
in children diagnosed with attention-deficit/hyperactivity disorder.
Chelonis JJ, Edwards MC, Schulz EG, Baldwin R, Blake DJ, Wenger
A, Paule MG.
Department of Psychology, University of Arkansas at Little Rock,
University of Arkansas for Medical Sciences-Arkansas Children's
Hospital, and National Center for Toxicological Research, 72204,
USA. jjchelonis@mail.ualr.edu
The effect of stimulant medication on recognition memory was
examined in 18 children with attention-deficit/hyperactivity disorder
(ADHD). Recognition memory was assessed using a delayed matching-to-sample
task at 6 delays ranging from 1 to 32 s. Each child was tested
on 2 separate occasions, once 60 to 90 min after taking stimulant
medication and the other at least 18 hr after taking medication.
Children performed significantly better on medication than off.
Stimulant administration significantly increased accuracy and
the number of nickel reinforcers earned. Decreases in observing
response latency and correct choice response latency occurred
after taking stimulant medication. The results indicate that stimulant
medication improved recognition memory for children with ADHD.
-----
World J Biol Psychiatry. 2002 Jul;3(3):150-5.
A pilot controlled trial of transdermal nicotine
in the treatment of attention deficit hyperactivity disorder.
Shytle RD, Silver AA, Wilkinson BJ, Sanberg PR.
Center for Infant and Child Development, Center for Aging and
Brain Repair, Departments of Psychiatry, Neurosurgery, Neuroscience
Program, University of South Florida, Tampa, Florida, USA. dshytle@hsc.usf.edu
OBJECTIVE: To test the hypothesis that transdermal nicotine
would be efficacious for the treatment of children and adolescents
with attention deficit hyperactivity disorder (ADHD). METHOD:
This was a double-blind, placebo-controlled, randomized, pilot
trial that compared the effects of daily transdermal nicotine
(5 mg/16 hrs) to placebo in children and adolescents with ADHD.
There was a three-day washout period of all psychotropic medication
followed by a one-week treatment period. RESULTS: All 10 subjects
enrolled (six males, four females; mean age = 10 years, SEM =
0.8) completed the study. As assessed by the 48-item Conners Parent
Rating Scale at endpoint and during the trial, there was a significantly
greater reduction in ADHD symptoms on "Learning Problems"
and "Hyperactivity" subfactors. Nausea, stomach ache,
itching under patch and dizziness were the most frequently reported
adverse effects associated with transdermal nicotine. CONCLUSIONS:
While the results of this study support previous research indicating
that nicotinic receptor modulation may be a potentially useful
strategy for the treatment of ADHD, therapeutic uses of nicotine
are limited due to side effects. Thus, future research should
investigate ways of improving the therapeutic index of nicotinic
ligands in the treatment of ADHD, such as testing selective nicotinic
antagonists alone or in combination with cholinergic agonists.
------
Pediatrics. 2002 Dec;110(6):e75.
Efficacy of atomoxetine versus placebo in school-age
girls with attention-deficit/hyperactivity disorder.
Biederman J, Heiligenstein JH, Faries DE, Galil N, Dittmann R,
Emslie GJ, Kratochvil CJ, Laws HF, Schuh KJ; Atomoxetine ADHD
Study Group.
Massachusetts General Hospital, Boston, Massachusetts, USA.
OBJECTIVE: The efficacy of atomoxetine was assessed in school-age
girls with attention-deficit/hyperactivity disorder (ADHD). Atomoxetine
is a potent inhibitor of the presynaptic norepinephrine transporter
with minimal affinity for other noradrenergic receptors or for
other neurotransmitter transporters or receptors. METHODS: A total
of 291 children who were 7 to 13 years of age and met Diagnostic
and Statistical Manual of Mental Disorders, Fourth Edition criteria
for ADHD participated in 1 of 2 combined, double-blind, placebo-controlled,
multisite, identical clinical trials. This intent-to-treat subset
analysis examined the effects of atomoxetine versus placebo in
51 girls who were randomized to atomoxetine (n = 30) or placebo
(n = 21) for 9 weeks. ADHD symptoms were assessed using parent-
and investigator-rated scales. RESULTS: Atomoxetine was superior
to placebo on the following measures: the Attention-Deficit Hyperactivity
Disorder Rating Scale-IV-Parent Version: Investigator Administered
and Scored Total Score; the Inattentive and Hyperactive/Impulsive
subscales of the Attention-Deficit Hyperactivity Disorder Rating
Scale-IV-Parent Version: Investigator Administered and Scored
Total Score; the ADHD Index subscale of the Conners' Parent Rating
Scale-Revised: Short Form; and the Clinical Global Impressions
of Severity of ADHD. Statistically significant efficacy was seen
1 week after randomization and remained so for the duration of
the study. One patient from each of the atomoxetine and placebo
groups discontinued the study as a result of an adverse event.
CONCLUSION: Atomoxetine was found to be effective and well tolerated
for the treatment of ADHD in school-age girls.
-----
J Clin Exp Neuropsychol. 2002 Sep;24(6):781-91.
Training of working memory in children with ADHD.
Klingberg T, Forssberg H, Westerberg H.
Department of Neuropediatrics, Karolinska Institute, Stockholm,
Sweden. torkel.klingberg@neuro.ki.se
Working memory (WM) capacity is the ability to retain and manipulate
information during a short period of time. This ability underlies
complex reasoning and has generally been regarded as a fixed trait
of the individual. Children with attention deficit hyperactivity
disorder (ADHD) represent one group of subjects with a WM deficit,
attributed to an impairment of the frontal lobe. In the present
study, we used a new training paradigm with intensive and adaptive
training of WM tasks and evaluated the effect of training with
a double blind, placebo controlled design. Training significantly
enhanced performance on the trained WM tasks. More importantly,
the training significantly improved performance on a nontrained
visuo-spatial WM task and on Raven's Progressive Matrices, which
is a nonverbal complex reasoning task. In addition, motor activity--as
measured by the number of head movements during a computerized
test--was significantly reduced in the treatment group. A second
experiment showed that similar training-induced improvements on
cognitive tasks are also possible in young adults without ADHD.
These results demonstrate that performance on WM tasks can be
significantly improved by training, and that the training effect
also generalizes to nontrained tasks requiring WM. Training improved
performance on tasks related to prefrontal functioning and had
also a significant effect on motor activity in children with ADHD.
The results thus suggest that WM training potentially could be
of clinical use for ameliorating the symptoms in ADHD.
-----
Am J Psychiatry. 2002 Nov;159(11):1896-901.
Once-daily atomoxetine treatment for children
and adolescents with attention deficit hyperactivity disorder:
a randomized, placebo-controlled study.
Michelson D, Allen AJ, Busner J, Casat C, Dunn D, Kratochvil C,
Newcorn J, Sallee FR, Sangal RB, Saylor K, West S, Kelsey D, Wernicke
J, Trapp NJ, Harder D.
Lilly Research Laboratories, Indianapolis, IN 46285, USA. dmichelson@lilly.com
OBJECTIVE: The authors assessed the efficacy of once-daily
atomoxetine administration in the treatment of children and adolescents
with attention deficit hyperactivity disorder (ADHD). METHOD:
In a double-blind study, children and adolescents with ADHD (N=171,
age range=6-16 years) were randomly assigned to receive 6 weeks
of treatment with either atomoxetine (administered once daily)
or placebo. RESULTS: Outcomes among atomoxetine-treated patients
were superior to those of the placebo treatment group as assessed
by investigator, parent, and teacher ratings. The treatment effect
size (0.71) was similar to those observed in previous atomoxetine
studies that used twice-daily dosing. Parent diary ratings suggested
that drug-specific effects were sustained late in the day. Discontinuations
due to adverse events were low (less than 3%) for both treatment
groups, and no serious safety concerns were observed. CONCLUSIONS:
Once-daily administration of atomoxetine is an effective treatment
for children and adolescents with ADHD.
-----
J Clin Psychopharmacol. 2002 Oct;22(5):468-73.
Comparative efficacy of Adderall and methylphenidate
in attention-deficit/hyperactivity disorder:
a meta-analysis.
Faraone SV, Biederman J, Roe C.
Pediatric Psychopharmacology Unit of the Child Psychiatry Service,
Massachusetts General Hospital, Boston. sfaraone@hms.harvard.edu
Because methylphenidate is currently the most widely prescribed
medication for attention-deficit/ hyperactivity disorder, several
studies have used it as the active comparator medication for evaluating
the efficacy of a newer stimulant, Adderall. These prior studies
show Adderall to be superior to placebo and suggest it is at least
as effective as the standard-release form of methylphenidate and
has a longer duration of action. Although these initial studies
provide useful information for clinicians treating children with
attention-deficit/hyperactivity disorder, they are difficult to
interpret because findings vary among studies and among the different
types of measures used within each study. To provide a clearer
picture of what conclusions can be drawn from these studies, we
performed a meta-analysis. Data from the four available studies
suggest that Adderall has a small but statistically significant
advantage over the standard-release form of methylphenidate. This
advantage was observed for both symptom measures and global ratings
but was strongest for global ratings. The effect of Adderall was
significant for clinician and parent ratings but not for teacher
ratings and was significant for both fixed-dose and best-dose
designs.
-----
Eur Arch Psychiatry Clin Neurosci. 2002 Aug;252(4):177-84.
Psychotherapy of attention deficit hyperactivity
disorder in adults—a pilot study using a structured skills
training program.
Hesslinger B, Tebartz van Elst L, Nyberg E, Dykierek P, Richter
H, Berner M, Ebert D.
Albert-Ludwigs-University, Department of Psychiatry and Psychotherapy,
Hauptstr 5, 79104 Freiburg, Germany. bernd_hesslinger@psyallg.ukl.uni-freiburg.de
In clinical practice many adult patients with attention deficit
hyperactivity disorder (ADHD) ask for an additional psychotherapeutic
intervention besides the medical therapy. In this paper we present
a structured skill training program particularly tailored for
adult patients with ADHD. The program is based on the principles
of cognitive-behavioral treatment for borderline personality disorder
developed by M. Linehan. It was modified to suit the special needs
of adult patients with ADHD. In this exploratory pilot study we
tested this program in a group setting. The following elements
were presented: neurobiology of ADHD, mindfulness, chaos and control,
behavior analysis, emotion regulation, depression, medication
in ADHD, impulse control, stress management, dependency, ADHD
in relationship and self respect. In an open study design patients
were assessed clinically using psychometric scales (Attention
Deficit Hyperactivity Disorder Checklist according to DSM-IV,
16 items of the SCL-90-R, Beck-Depression Inventory, visual analogue
scale) prior to and following group therapy. This treatment resulted
in positive outcomes in that patients improved on all psychometric
scales.
-----
Ann Clin Psychiatry. 2002 Jun;14(2):105-11.
Attention deficit disorder in adults.
Pary R, Lewis S, Matuschka PR, Rudzinskiy P, Safi M, Lippmann
S.
Department of Veterans Affairs, Mental Health, and Behavioral
Science Service, Louisville, Kentucky 40206, USA.
ADHD/ADD, once thought to occur only in children, is now recognized
as continuing into adulthood in many people. In order to be labeled
as such, signs and symptoms must start before age 7 and are primarily
characterized by inattention, distractibility, and impulsiveness.
Although the exact mechanism is unknown, a number of associated
neurochemical and structural abnormalities have been observed.
This disorder can negatively affect the educational, social, and
occupational lives of those who suffer from its symptoms. It interferes
with the ability to establish and maintain close relationships.
Pharmacotherapy remains the primary mode of treatment. Stimulants
such as dextroamphetamine and methylphenidate are the main drugs
utilized; they are available in immediate and longer duration
versions. Bupropion is another important medicinal option, and
there are a variety of other miscellaneous medications to consider,
including modafinil, venlafaxine, tricyclic antidepressants, and
guanfacine. Psychotherapy is shown to help control impulsiveness,
form more satisfactory relationships, rear children more effectively,
and improve organizational and problem-solving skills.
-----
Drugs. 2002;62(13):1899-904; discussion 1905-8.
Dexmethylphenidate.
Keating GM, Figgitt DP.
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Dexmethylphenidate comprises only the d-enantiomer (the pharmacologically
effective isomer) of racemic methylphenidate and is indicated
for the treatment of patients aged > or =6 years with attention
deficit hyperactivity disorder (ADHD). In a 4-week, double-blind
trial in 132 children with ADHD, significantly greater improvements
from baseline in teacher-rated Swanson, Nolan and Pelham (SNAP)-ADHD
scores were seen in dexmethylphenidate and methylphenidate recipients,
compared with placebo recipients. In addition, significantly more
dexmethylphenidate and methylphenidate recipients, compared with
placebo recipients, were much improved or very much improved according
to Clinical Global Impression-Improvement of Illness scale scores.
In the same study, parent-rated SNAP-ADHD scores had decreased
by a significantly greater extent in dexmethylphenidate recipients
at 3pm and 6pm and in methylphenidate recipients at 3pm, compared
with placebo recipients. Significantly fewer dexmethylphenidate
than placebo recipients failed treatment in a double-blind, treatment-withdrawal
trial in 75 children with ADHD (17.1 vs 61.5%). In a noncomparative
study in 22 children with ADHD, symptoms of ADHD, as assessed
by teachers and parents, were controlled during the entire school
day in 68 and 86% of dexmethylphenidate recipients, respectively,
with a median duration of effect of 6.3 and 7.5 hours, respectively.
Dexmethylphenidate was generally well tolerated in children with
ADHD; adverse events were consistent with those known to be associated
with agents containing methylphenidate.
-----
Pediatr Neurol. 2002 Apr;26(4):261-6.
Methylphenidate treatment.
Weber P, Lutschg J.
University Children's Hospital, Department of Neuropediatrics,
P.O. Box, CH-4005, Basel, Switzerland.
Methylphenidate is the psychotropic drug most commonly used
to treat individuals suffering from developmental attention-deficit-hyperactivity
disorder. Additional attention deficit is part of numerous neurologic
diseases in childhood. Despite the vast extent of scientific research
on methylphenidate, the use of this stimulant in the treatment
of cognitive and behavioral dysfunction in children with epilepsy,
brain tumor, leukemia, closed brain injury, encephalitis, meningitis,
or mental retardation continues to be controversial. Only few
data exist about the efficacy and side effects of methylphenidate
treatment in children with this neurologic illness or history.
The aim of the present study is to provide a review of this important
clinical topic and perhaps to stimulate further controlled investigations.
©Copyright 1992-date by The Center
for Current Research. The Attention-Deficit/Hyperactivity Disorder
File is a proprietary compilation of the Center for Current Research.
The information in the File is solely for your use, and the use
of your family, friends, and doctors. The information is the property
of the individual researchers and institutions that produced it.
It is an infringement of copyright law to attempt to "resell"
the information as it is presented here.
|
