Atomoxetine in Children with ADHD

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Bottom line: Atomoxetine may or may not be a reasonable alternative to ritalin for kids with ADHD

Clinical Question: In your clinic, you see an 11 year old boy with ADHD who is not responding to ritalin. Increasing the dosage causes the child to have insomnia and headaches. Is there an alternative tx?

Article: Kratochvil, Christopher, et al. 2002. Atomoxetine and Methylphenidate Treatment in Children with ADHD: A Prospective Randomized, Open Label Trial. J Am Acad Child Adolesc Psychiatry 41(7):776-84.

Background:

1. ADHD affects 3-7 percent of school age children
2. Affecting the dopaminergic and noradrenergic pathways have resulted in improved impulse control and concentration.
3. Atomoxetine is a potent inhibitor of the presynaptic norepinephrine transporter with minimal affinity for other neurotransmitters.

Methods:

1. Design - 10 week randomized, open label tx with either atomoxetine or ritalin. 319 patients were entered, and 228 were randomized (44 for ritalin, 184 for atomoxetine). 24 were dropped off in the Duke ER by parents and were lost to follow up.
2. Randomization - 3:1 (atomoxetine to ritalin) for first block, then 5:1 blocks (atomoxetine to ritalin)
3. Inclusion - boys 7-15 and girls 7-9 (pregnancy issues) who met ADHD DSM criteria. All children had severity score at least 1.5 SD from average.
4. Exclusion - Bipolar, psychosis, motor tics/ tourettes, substance abuse, prior failure with methylphenidate.

Efficacy Variables:

1. Primary scale was ADHD RS - an 18 item DSM IV based scale. Based on interview with parent.
2. Parent rated scale also implemented as a "T-score." 50 was the norm and every 10 points represented one SD.
3. Other scales include the conners parent rating scale (CPRS -R), CTRS-R (conners teacher), CGI severity
4. CYP2d6 status - pt's grouped under poor and extensive metabolizers (homozygotes at any of 6 alleles in a gene were deemed poor metabolizers. Poor metabolizers had dose titration of 1mg/kg per day, vs. 2mg/kg per day for extensive metabolizers. Ritaline pushed up for clinical need, not to exceed 60mg/day

Analysis: ANCOVA, LOCF

Validity:

1. Randomization - yes, but not blinded.
2. Follow up of patients sufficiently long and complete? decent
3. Were all patients analyzed in the groups to which they were randomized? yes
4. Were the groups similar at the start of the trial? OPEN LABEL
5. Were groups treated equally, apart from the experimental therapy? OPEN LABEL

Results:

1. 66/184 in atomoxetine and 19/44 ritalin patients dropped out (see table one for demographic info).
2. Of 228 patients, 218 came for at least one f/u and were included in results
3. Final mean dose for atomoxetine among extensive metabolizers (n= 174) was 1.40mg/kg/day. Poor metabolizers (n=10) had average dose of 0.48mg/kg/day.
4. Adverse Events - 5.4% of atomoxetine and 11.4% of ritalin group withdrew secondary to adverse effects.
5. Adverse Effects - Statistically significant increase in pulse and BP for both atomoxetine and ritalin. Headache the most common side effect in each group. Atomoxetine group lost 0.63kg in 10 wks, compared to 0.13 wks in Methylphenidate.

Comments: Open label trial, so difficult to say if bias was properly accounted for, but authors claim that placebo effect in ADHD trials are low to begin with. With the exception of weight, atomoxetine may at least be as safe as methylphenidate. French Fries are good.