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STANLEY P. KUTCHER, M.D., EDITOR
MINI REVIEW
CONTENTS
Atomoxetine
Mini Review
• Atomoxetine
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 New Research
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 Anxiety Disorder
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 Personality Disorder
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- Children
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 HANDOUT INCLUDED:
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 Bruce Ferguson
so–called “slow” or “poor” metabolizers David Gardner
“extensive metabolizers” or EMs. In the Barbara Geller
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 (Feb, Mar, May, June, Aug, Sept, Nov, and Dec) by The Guilford Press, 72 Spring Street, New York, NY 10012. Periodicals postage paid at New York, NY, and SUBSCRIPTION PRICE: Volume 9, 2004 (eight issues) Individuals $150.00 ($160.00, Canada and for-eign) and Institutions, $225.00 ($235.00, Canada and foreign). Orders by MasterCard, VISA, or American Express can be placed by phone at 800-365-7006, Fax212-966-6708, or E-mail news@guilford.com; in New York, 212-431-9800. Payment must be made in U.S.
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This publication is intended to provide accurate and
authoritative information regarding the subject matter
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The recommended doses of medications cited in
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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 Adolescent Pharmacology 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 Adolescent Psychopharmacology 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 E-mail: Tim.Yates@CalgaryHealthRegion.ca Disorder. Journal of Child and Adolescent Michelson, D. et al. (2001). Atomoxetine in the Psychopharmacology News, 13(1), 53-63.
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