Atomoxetine. Attention-deficit/hyperactivity disorder: no better than methylphenidate

Abstract

When attention deficit-hyperactivity disorder in children is truly problematic, methylphenidate, an amphetamine, can be tried as a last resort. Methylphenidate has short-term symptomatic efficacy but also many adverse effects, including a risk of sudden death. After having been evaluated, unsuccessfully, in depression, atomoxetine, a noradrenaline reuptake inhibitor, was authorised in some EU member states for use in attention-deficit/hyperactivity disorder. In France it has only received temporary authorisation for prescription on a named-patient basis. Two double-blind trials comparing atomoxetine versus methylphenidate provided somewhat different results, based on a symptom rating scale completed by the investigator after an interview with the parents. In a trial in 516 children treated for 6 weeks, the "response" rate was statistically higher than with methylphenidate (56% versus 45%). In the other trial in 330 children treated for 8 weeks, the response rate was about 80% in both groups. A meta-analysis of 9 placebo-controlled trials in a total of 1828 children showed that atomoxetine was more effective than placebo in the short term. The main adverse effects identified in clinical trials and pharmacovigilance studies conducted in the United Kingdom and the United States were gastrointestinal disorders (abdominal pain, reduced appetite, vomiting, and weight loss) and neuropsychological disorders (drowsiness, irritability, mood swings, aggressive behaviour). A meta-analysis of 12 trials and pharmacovigilance studies showed an increased risk of suicide. Atomoxetine also provokes seizures, arterial hypotension, tachycardia, and hepatic disorders. Little is known about the risk of abuse or dependence, or the long-term efficacy of treatment. Atomoxetine carries a risk of multiple drug interactions due to its metabolism by the cytochrome P450 isoenzyme 2D6 and its inhibitory effect on noradrenaline reuptake. In practice, atomoxetine has a similar safety profile to methylphenidate and is probably less effective. When drug therapy is warranted, it is better to continue to use methylphenidate, despite its adverse effects.