Leo Sher, M.D.

Our research report, “Treatment of suicide attempters with bipolar disorder: a randomized clinical trial comparing lithium and valproate in the prevention of suicidal behavior” was published in the October 2011 issue of the American Journal of Psychiatry (1). In our double-blind, randomized, parallel-group study, we tested the hypothesis that lithium offers bipolar patients with a history of suicide attempt greater protection against suicidal behavior compared to valproate.

To be included, patients had to have a DSM-IV diagnosis of a bipolar disorder (bipolar I or II disorder or bipolar disorder not otherwise specified) based on the Structured Clinical Interview for DSM-IV; be in a depressive or mixed episode; have at least one past suicide attempt; and be 18 to 75 years of age. Patients were randomly assigned to treatment with lithium or valproate, plus adjunctive medications as indicated, in a double-blind 2.5-year trial. We aimed to maintain patients on therapeutic dosages of lithium or valproate for the duration of the study. An intent-to-treat analysis was performed using the log-rank test for survival data. Two models were fitted: time to suicide attempt and time to suicide event (attempt or hospitalization or change in medication in response to suicide plans).

Average time in the study was not significantly different between the lithium and valproate groups. There were 45 suicide events in 35 participants, including 18 suicide attempts made by 14 participants, six from the lithium group and eight from the valproate group. There were no suicides. The event rate did not vary by sex. Intent-to-treat analysis using the log-rank test showed no differences between treatment groups in time to suicide attempt or to suicide event. Post hoc power calculations revealed that the modest sample size, reflective of challenges in recruitment, only permits detection of a relative risk of 5 or greater.

Contrary to our hypothesis, this randomized controlled trial revealed no difference in time to suicide attempt or suicide event between patients treated with lithium and those treated with valproate. The high rates of suicide attempts in both medication groups highlight the challenge of treating very suicidal patients.

Reference

1. Oquendo MA, Galfalvy HC, Currier D, Grunebaum MF, Sher L, Sullivan GM, Burke AK, Harkavy-Friedman J, Sublette ME, Parsey RV, Mann JJ. Treatment of suicide attempters with bipolar disorder: a randomized clinical trial comparing lithium and valproate in the prevention of suicidal behavior. Am J Psychiatry. 2011 Oct;168(10):1050-6. doi: 10.1176/appi.ajp.2011.11010163. Epub 2011 Jul 18.