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FILLERS: Second generation antidepressants should remain an option for children and adolescents with depression or anxiety BMJ 2007; 335: 607 [Abstract] [Full text]

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Skepticism about antidepressants for under 18s

David B Menkes, Jon N Jureidini, Peter R Mansfield   (22 September 2007)

Skepticism about antidepressants for under 18s 22 September 2007
David B Menkes, Associate Professor Waikato Clinical School, Hamilton 3240, New Zealand, Jon N Jureidini, Peter R Mansfield Send response to journal: Re: Skepticism about antidepressants for under 18s	An anonymous BMJ Update (1) describes a meta-analysis concluding that benefits outweigh harms in the antidepressant treatment of children and adolescents (2). This conclusion warrants skepticism for several reasons. First, Bridge et al treat responder status and suicidality (ideation or attempts) as though they were opposite but equal. For depression, 10% more responded to antidepressants than to placebo, whilst 1% more subjects had at least one episode of suicidality. This numerical difference is taken as showing that benefit outweighs harm. However, the difference between responders and non-responders is often no more than a few points on a continuous rating scale; difference scores between antidepressant and placebo groups are often of little or no clinical significance (3). By contrast, there is a categorical and life-threatening difference between children who do and don’t have suicidal ideation or attempts. Second, the authors calculated suicidality per individual rather than per act. More children on antidepressants exhibited multiple acts, and more serious acts, than those on placebo. Similarly, the authors chose to use the more conservative of the two datasets considered by the US Food and Drug Administration in its analysis of antidepressant-induced suicidality (4). This dataset is likely to underestimate the problem; for example, the category ‘self injury with intent unknown’ is excluded. Third, the claim that there were no suicides in the trials is uncertain because some were lost to follow up. Fourth, suicidality was the only harm considered by Bridge et al. They did not mention other common adverse effects including hostility and drug withdrawal. Nor did they consider the possibility of long-term adverse effects of antidepressants on young peoples’ physical and/or psychological development. Whilst antidepressants can be beneficial, recent trial (5) and case- control data show excess suicidality and completed suicide in young people (6). Together with concerns about the quality of paediatric antidepressant trials (7), such findings bedevil clinician guidance. On the basis of available evidence, we believe routine use of these drugs is unjustified. There may be merit in exploiting the 32-50% ‘placebo’ response (NNT = 2-3) (2) and proceeding to antidepressants, cautiously, if this fails. 1. Anonymous. Second generation antidepressants should remain an option for children and adolescents with depression or anxiety. BMJ 2007;335:607. 2. Bridge JA, Iyengar S, Salary CB, Barbe RP, Birmaher B, Pincus HA, Ren L, Brent DA. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta- analysis of randomized controlled trials. JAMA 2007;297:1683-96. 3. Moncrieff J, Kirsch I. Efficacy of antidepressants in adults. BMJ 2005;331:155-7. 4. Hammad TA, Laughren T, Racoosin J. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry 2006;63:332-9. 5. Apter A, Lipschitz A, Fong R, Carpenter DJ, Krulewicz S, Davies JT, Wilkinson C, Perera P, Metz A. Evaluation of suicidal thoughts and behaviors in children and adolescents taking paroxetine. J Child Adolesc Psychopharmacol 2006;16:77-90. 6. Olfson M, Marcus SC, Shaffer D. Antidepressant drug therapy and suicide in severely depressed children and adults: A case-control study. Arch Gen Psychiatry 2006;63:865-72. 7. Jureidini JN, Doecke CJ, Mansfield PR, Haby MM, Menkes DB, Tonkin AL. Efficacy and safety of antidepressants for children and adolescents. BMJ 2004;328:879-83. Competing interests: JNJ and PRM have no competing financial interests to declare. DBM has been a paid expert witness on behalf of plaintiffs in civil cases defended by antidepressant manufacturers Eli Lilly and Pfizer.