STANLEY P. KUTCHER, M.D., EDITOR MINI REVIEW CONTENTS Atomoxetine Mini Review
Tim Yates, B.S.C., M.D.C.M., F.R.C.P.
• Clinically Useful Approaches
Atomoxetine (ATX) is a selective norepinephrine (NE) reuptake inhibitor that was
for the Atypical Antipsychotics
approved as a treatment for ADHD in the United States in November 2002. It was
(Second Generation Antipsychotics) in Pediatric
launched there in January 2003: Its approval and launch in Canada is pending. Psychotic Disorders
What is of particular interest about ATX is that it has a 24–hour effect on ADHD
signs and symptoms (albeit diminishing gradually towards the following morning)on a once–daily morning dosing schedule. Unlike the psychostimulants it is not a
controlled substance, it is less likely to cause insomnia in children and it does not
• Fluoxetine and CBT in Generalized Social Anxiety Clinical Applications
• Paroxetine in Children and Adolescents With Social
Studies of ATX using the ADHD Rating Scale (ADHD RS), the Conners Parent
Rating Scale–Revised (CPRS–R) and other validated ADHD measures have shown
• Olanzapine in Schizotypal
a beneficial clinical effect on the signs and symptoms of ADHD significantly greater
than placebo and similar to those of IR–MPH. Of these eight studies five were ran-
• Treatment–Emergent Mania in
domized and placebo–controlled while three were open–label including the com-
parison with MPH. There have been no negative trials to date.
ATX is equally effective against inattention and hyperactivity/impulsivity. This
clinical effect has been demonstrated in children, adolescents and adults; withADHD alone and with a range of comorbidities.
In children and adolescents, teachers and parents were in agreement about the
diminution of ADHD–related problems. In the classroom, teachers rated ATX as
Abstracts from the Canadian 24th Annual Conference,
improving childrens’ functioning irrespective of comorbid ODD or LD and prior
Canadian Academy of Child
stimulant response. Conners CGI scores were significantly improved while ratings of
and Adolescent Psychiatry
academic performance (APRS, p = .106), social skills (SSRS–T, p = .196), and prob-lem behavior (p=.025) each showed some improvement.
Beyond the first–line criteria for ADHD, ATX has proven superior to placebo in
improving CHQ measures of self–esteem, psychosocial functioning, parent impactand family activity. The improvements in family–related parameters are linked toATX’s continuing effect into the evening.
Child & Adolescent Psychopharmacology News
is an independent publication that accepts noadvertising or other outside support. CAPN • 1 Pharmacodynamics
pregelatinized starch and dimethicone. Stanley P. Kutcher, M.D., Editor Normand Carrey Mina K. Dulcan
ability in the rate of its breakdown. Five
so–called “slow” or “poor” metabolizers
“extensive metabolizers” or EMs. In the
Washington University School of Medicine,
serum half–life is about 5 hours. In the
Laurence Greenhill Rachel G. Klein Lili Kopala James T. McCracken
abruptly; no tapering of dose is required. Mark Riddle
John Hopkins Medical Institute, Baltimore, MD
Neal Ryan Jovan Simeon Child & Adolescent Psychopharmacology News
(ISSN 1085-0295) is published eight times per year
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Photocopying of this newsletter is not permitted. IMPORTANT NOTICE This publication is intended to provide accurate and authoritative information regarding the subject matter covered. It is sold with the understanding that the pub- lisher is not engaged in rendering medical, psychologi- cal, financial, legal, or other professional services. The recommended doses of medications cited in this newsletter are not meant to serve as a guide for prescribing of medications.
Physicians, please check the manufacturer’s product
information sheet or the PHYSICIAN’S DESK REF- ERENCE for further information and contraindica-
the evening and the following morning.
significant clinical benefit beginning at
CAPN • 2
different titration strategies, different
populations, different cut–offs for in-
plaints were about anorexia (24% vs.
magnitude of this effect is, to a degree,
nolence, fatigue, sedation, dizziness) at
ritability, aggression, emotional distur-
monoamine levels than 1 mg/Kg doses.
tis has been reported quite frequently in
be the result of a highly specific inhibi-
lowers the risk of drug–activated move-
lence and “asthenia”, and GI–related
pus striatum (a pleasure/reward area) its
diarrhea. In dose–response study the in-
sion. This latter point is buttressed by a
CAPN • 3
etc. A few did so because of lack of effi-
dysregulation syndrome” that falls short
non–significanly to be in higher dosage
Safety and Tolerability
medication is very likely to be effective
of tics; in some children their tics were
although not to a level of statistical sig-
subjects by week 8 there was a slight in-
and erectile dysfunction (10% vs. 1%).
if some other mechanism was at work. Brown University Child and AdolescentPharmacology Update a consultation let-
risk of mydriasis and its use is not rec-
urticaria, and rash have been noted.
years. Clearly there is a long–term ef-
tures for several days before returning to
to overdose with ATX alone. In ‘pure’
the velocity of growth over the first six
where the patient was also taking ATX.
from the baseline height and weight. CAPN • 4 References
With Attention-Deficit/Hyperactivity Disor-der: A randomized, Placebo-Controlled,
Dose-Response Study. Pediatrics, 108(5), E83.
Girls With Attention-Deficit/Hyperactivity
Disorder. Pediatrics, 110(6).
Adolescents With Attention-Deficit/Hyper-
Bymaster, F.P. (2002). Atomoxetine Increases
Extracellular Levels of Norepinephrine and
cebo-Controlled Study. American Journal of
Dopamine in Prefrontal cortex of Rat: A Po-
Psychiatry, 159, 11, 1896-1901.
tential Mechanism for Efficacy in Attention
Michelson, D. et al. (2003). Atomoxetine in
Neuropsychopharmacology, 27( 5), 699-711.
cebo-Controlled Studies,( Biological Psychia-
Bymaster, F.P. et al. (2003). Atomoxetine, A
Newcorn, J. (2003). The Brown University Child
Noradrenergic Neurotransmission. Neurosci-
and Adolescent Pharmacology Update, 5(11), 1,
ence Research division, Lilly Research Labo-
Atomoxetine, ADIS Drug profile, Adis Inter-
national Inc., Yardley PA. Pediatric Drugs,
Atomoxetine Increases Extracellular Levels of
Norepinephrine and Dopamine in Prefrontal
Spencer, T. et al. (2001). An Open-Label,
Cortex of Rat: A Potential Mechanism for Ef-
Dose-Ranging Study of Atomoxetine in Chil-
ficacy in Attention Deficit Hyperactivity Dis-
dren With Attention-Deficit/Hyperactivity
order. Presented at the Canadian College of
Disorder. Journal of Child and AdolescentPsychopharmacology News, 11(3).
Spencer, T. et al. (2002). Results From 2
Heil, S.H. et al. (2002). Comparison of the sub-
Proof-of-Concept, Placebo-Controlled Stud-
jective, physiological, and psychomotor ef-
ies of Atomoxetine in Children With Atten-
fects of atomoxetine and methylphenidate in
tion-Deficit/Hyperactivity Disorder. Journal of
light drug users. Drug and Alcohol Dependence,
Clinical Psychiatry, 63(12), 1140-1147.
Atomoxetine on Growth in Children and Ad-
olescents with ADHD. Presented at The Eu-
uous Symptom Relief. Lilly Research Labora-
Psychiatry (ESCAP), Paris, Sept. 28-Oct. 1,
Kratchovil, C.J. et al. (2002). Atomoxetine and
Weiss, M., Tannock, R. et al. Controlled Study of
Once-Daily Atomoxetine in the School Set-
accounts for much of its popularity.
Open-Label Trial. Journal of American Acad-
ting. Presented at the Canadian College of
emy of Child and Adolescent Psychiatry, 41(7),
McCracken, J.T., Sallee, F.R., Leonard, H.L., et
Wernicke, J.F., & Kratochvil, C.J. (2003). Safety
Profile of Atomoxetine in the Treatment of
in children with tic disorders. Poster at
Children and Adolescents With ADHD. Jour-Dr. Tim Yates is an Associate Professor of Psy-nal of Clinical Psychiatry, 63(12), 50-55. chiatry and Pediatrics, Faculty of Medicine,
atomoxetine for ADHD. The Brown Univer-University of Calgary, Alberta, Canada.sity Child and Adolescent Pharmacology Update,
cents with Attention Deficit Hyperactivity
Disorder. Journal of Child and Adolescent
Michelson, D. et al. (2001). Atomoxetine in the
Psychopharmacology News, 13(1), 53-63. www.guilford.com
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Irreducible characters which are zero on onlyInstitute of Advance Studies in Basic Sciences, Zanjan, IranSuppose that G is a …nite solvable group which has an irreduciblewhich vanishes on exactly one conjugacy class. show that G has a homomorphic image which is a nontrivial 2-transitivepermutation group. The latter groups have been classi…ed by Huppert. We can also say more about the struc
Het verhaal van de wolf in een verkeerde wereld Vaak kom je tijdens je leven steeds hetzelfde tegen, vaker dan je op basis van toeval kunt verwachten. ‘De geschiedenis verhaalt zich’, heet dat dan. Het verhaal van Wolf is daar een markant voorbeeld van. Ik leerde Wolf kennen tijdens een avondvierdaagse via de stichting. (Hij heet niet echt zo.) Hij heeft iets met wolven. Het