The International Journal of Neuropsychopharmacology



Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials: a replication analysis of the Food and Drug Administration Database


Arif  Khan  a1 a2 c1, Shirin R.  Khan  a1, Robyn M.  Leventhal  a1 and Walter A.  Brown  a3
a1 The Northwest Clinical Research Center, Bellevue, WA, USA
a2 The Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA
a3 The Department of Psychiatry, Brown University, Providence, RI, USA

Abstract

The assumption that depressed patients who are assigned to placebo in antidepressant clinical trials are exposed to substantial morbidity and mortality has not been based on research data. Because of worldwide concern about placebo use and the implications of our earlier findings of no increased suicide risk in placebo-treated patients, we conducted a replication study in a new patient sample. We assessed suicide risk and symptom reduction among placebo-treated patients participating in antidepressant clinical trials for two recently approved antidepressants, venlafaxine ER and citalopram, which were unavailable during our previous study. Among 23201 participant patients, 32 committed suicide and 172 attempted suicide. Rates of suicide and attempted suicide did not differ significantly among the placebo- and drug-treated groups. Based on patient exposure years, annual rates of suicide and attempted suicide were 0.5 and 6.7% with placebo, 0.9% with active comparator (rates for attempted suicide are unavailable), and 0.6 and 6.3% with investigational antidepressants. Symptom reduction was 47.9% with investigational drugs (n = 1172), 47.5% with active comparators (n = 161), and 35.5% with placebo (n = 606). These data may inform discussions about the use of placebo in antidepressant clinical trials.

(Received August 20 2000)
(Reviewed November 20 2000)
(Revised November 27 2000)
(Accepted December 3 2000)


Key Words: Placebo; suicide and antidepressant treatment; placebo problem; placebo-controlled trials; randomized controlled trial.

Correspondence:
c1 Address for correspondence: Dr A. Khan, 1900 116th Ave NE no. 112, Bellevue, WA 98004, USA. Tel.: (425) 453 0404 Fax: (425) 453-1033 E-mail: arif@accessone.com


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