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Antidepressants and Suicide: WHO Scientists Weigh InAntidepressants and suicide: What we don't know harms children.
Published on February 4, 2009 by Peter D. Kramer in In Practice
On the question of new antidepressants and suicide, the evidence we have has been synthesized, and the results are in: the medications prevent suicides in adults, and especially in the elderly. For children and adolescents, we simply don't know - and the gap in our knowledge has had dangerous effects.
World Health Organization scientists based in Italy and Canada have re-analyzed data on over 200,000 patients with depression treated with serotonergic antidepressants, or SSRIs. With a pool this large, the researchers were able to look past ideation to actual attempts or completed suicides.
The study found a strong protective effect for adults, including young adults, aged 18 to 25, and the elderly, over age 65. The medications decreased the risk of suicide by over 40 per cent in adults aged 18 to 64, and by over 50 per cent in older patients. These results are striking, especially in the light of earlier FDA summaries that found a neutral effect for non-elderly adults and a negative effect for young adults. But the FDA reports were based on research not designed to investigate suicidality, and the data were skewed conservatively, that is, in ways that might over-identify suicidal behavior. The new analysis is more clear-cut; it moves the line of high risk down from age 25 to age 18.
What happens below age 18 is uncertain. Both the FDA summary and yesterday's analysis found a marked increase in suicidality in depressed adolescents treated with SSRIs. (Unless I'm reading the data wrong, the risk for youth looks to be almost double on medication.) But as an accompanying editorial indicates, a large body of research points in the opposite direction. For instance, examining all youth suicides (42 deaths) over a five-year period, Danish pathologists found that none of the adolescents had been on SSRIs. In many countries, studies have found that low SSRI prescribing levels correlate with high youth suicide rates. Decreased SSRI prescribing since the FDA issued its "black box" warning has been associated with increased rates of suicide in adolescents. And some of the studies (including ones in the current WHO analysis) that have demonstrated an increase in suicidality are poorly controlled, so that the young people on SSRIs may be more seriously ill than those in the comparison group.
We need to settle this issue: As regards risk of suicide, do SSRIs help or harm depressed adolescents? The editorial assessing the WHO study contains these disturbing sentences: "Alarmingly, concerns about the risk of suicide in youth have led not only to fewer SSRI prescriptions without substitution of alternative medications or psychotherapies, but also to a decrease in predicted rates of diagnosis of mood disorders. Since a decrease in the rate of true depression is improbable, clinicians may be avoiding making this diagnosis to avoid the dilemma of whether to prescribe antidepressants to children or adolescents." This worry was one that experts raised when the FDA was considering its action - that a warning, however carefully worded, might cost lives. (I should note that on balance I favored the black box warning.) As the editorial indicates, "in youth, suicide appears to occur most commonly among those with untreated mood disorders."
My own impression - I discuss it in Against Depression - is that antidepressants simply work less well in children, and for reasons that accord well with the prevailing neurobiological theories of mood disorder. But when the medications do appear to help, are they dangerous? The new study again raises special worries about Paxil and also Effexor in young patients.
Incidentally, two of the WHO researchers on the new study, Andrea Cipriani and Corrado Barbui, were also authors of the widely publicized recent summary analysis that rated the relative merits of antidepressants. As in the prior report, in the new one Zoloft looks especially safe, at least in adults.