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November 2008

Metformin for Antipsychotic-Associated Weight Gain
Most studies with metformin (Avandamet and others) suggest that it attentuates weight gain or actually promotes weight loss in patients who are taking antipsychotics.

In Brief
Valproate Teratogenicity Increased by High Dose, Concomitant Drugs;Celecoxib, Naproxen Do Not Protect Against Alzheimer's Disease

Atomoxetine versus Methylphenidate for Pediatric ADHD
Methylphenidate (Ritalin and others) appears to be more efficacious than atomoxetine (Strattera) for treating attention-deficit/hyperactivity disorder in children but has more adverse effects.

Rivastigmine (Exelon) Patch
A transdermal system for delivering rivastigmine (Exelon) is now available in the United States for treating dementia associated with Alzheimer's or Parkinson's disease.

Atomoxetine versus Methylphenidate for Pediatric ADHD

November 2008

The selective norepinephrine reuptake inhibitor atomoxetine (Strattera) was approved by the US Food and Drug Administration (FDA) in 2002 for the treatment of attention-deficit/hyperactivity disorder (ADHD). How does it compare to older ADHD treatments, such as methylphenidate (Ritalin and others)? Newcorn and coworkers report on a placebo-controlled, double-blind trial that contrasted atomoxetine with the most frequently used and longest-acting methylphenidate formulation, an osmotically released preparation.1

Four hundred forty-two children and adolescents, aged 6 to 16 years, were randomly assigned to take one of three treatments for 6 weeks: atomoxetine, 0.8 to 1.8 mg/kg/day, in a divided twice-daily dose; osmotically released methylphenidate, 18 to 54 mg/day, as a single morning dose; or placebo. After the 6-week trial was completed, subjects originally assigned to the methylphenidate preparation were switched under double-blind conditions to atomoxetine for 6 weeks.

"Response" was at least a 40% improvement in ADHD scores. Response rates after the first 6 weeks were: methylphenidate, 56%; atomoxetine, 45%; and placebo, 24%. Both active treatments were superior to placebo, but methylphenidate "beat" atomoxetine to a significant degree. The number needed to treat (NNT) for atomoxetine was 5, but methylphenidate did even better, with an NNT of 3. Patients who had never previously taken a stimulant medication had comparable response rates between methylphenidate and atomoxetine, suggesting that prior stimulant treatment may be an important variable. Rates of discontinuation of treatment due to adverse events were low and similar for all three treatments.

The side effects that were significantly different from placebo for both drugs were decreased appetite, increased diastolic blood pressure, and weight loss. There were no significant differences in systolic blood pressure among the three groups. The magnitude of mean weight loss was greater with methylphenidate (0.9 kg [2.0 lb]) than with atomoxetine (0.6 kg [1.3 lb]). Insomnia was more common with methylphenidate, while somnolence occurred more often with atomoxetine. Heart rates increased significantly more with atomoxetine than with placebo or methylphenidate.

One hundred seventy-eight subjects who had taken methylphenidate were switched to atomoxetine for the second 6 weeks. Of 70 patients who did not initially respond to methylphenidate, 30 (43%) responded to a subsequent trial with atomoxetine.

Overall, about one-third of subjects in the crossover group responded to either methylphenidate or atomoxetine but not both. About half responded robustly to both treatments. Of the other half, about two-thirds responded preferentially to one treatment, divided approximately equally between methylphenidate and atomoxetine, and roughly 22% were nonresponders to both treatments.

Methylphenidate appears to be the more efficacious treatment, albeit with more adverse effects. In an accompanying editorial, Vitiello points out that the study was too short to measure impact on functioning and long-term safety, such as growth suppression.2 He opines that a response to one but not the other treatment may be genetically related.

As in so many areas of psychiatry, treatment of pediatric ADHD remains one of trial and error. Patients who do not respond to methylphenidate or to atomoxetine may respond to the other, suggesting the wisdom of sequential trials. And each medication has its own side effects and risks (BTP 2008;31:35).

1Newcorn JH, Kratochvil CJ, Allen AJ, Casat CD, Ruff DD, Moore RJ, Michelson D, Atomoxetine/Methylphenidate Comparative Study Group: Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: Acute comparison and differential response. Am J Psychiatry 2008;165:721-730.

2Vitiello B: Improving decision making in the treatment of ADHD. Am J Psychiatry 2008;165:666-667.