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Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence

BMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h4320 (Published 16 September 2015) Cite this as: BMJ 2015;351:h4320

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Re: Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence

Faced with the suicidal events in Study 329, Drs Verdolini and Agius invite readers to consider the underlying neurobiology but their letter has no links to neurobiology whatsoever. It offers a series of claims regularly made by those with a mania for bipolar disorder. There is no link in these claims to biology and it is not clear that there is any clinical footing to the claims either.

For the record, healthy volunteers become suicidal on serotonin reuptake inhibitors. Are all of these bipolar? The rate of suicidal events on SSRIs in non-depressive indications is roughly the same as it is in depression - are these eating disorder and other patients all bipolar?

The rate of suicidal events on anticonvulsant supposed mood stabilizers in clinical trials of bipolar disorder is roughly double the placebo rate in the same trials - the results map onto the rates for suicidal events in antidepressant trials. It goes without saying these suicidal patients actually bipolar but offering this as an explanation would be ridiculous.

The rate of suicidal events in trials of anticonvulsants used for migraine and epilepsy is again similar to that in bipolar disorder trials - what are we to make of this.

What are we to make of the fact that the rate of suicidal events in antipsychotic trials is also roughly similar - regardless of indication?

A much more parsimonious hypothesis is that certain drugs do not suit certain individuals. We have no idea what the biology is in these cases. We do not even know why some patients on SSRIs become intensely nauseated and others do not - a much more common side effect that suicidality. To suggest that we do know what is going on by bringing bipolar disorder into the frame, a disorder whose biology remains quite opaque, is not helpful

Competing interests: As outlined in Restoring Study 329

09 December 2015
David Healy
Professor of Psychiatry
Hergest Unit, Wales LL57 2PW