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Do Antidepressants Make Patients Suicidal?

Suicide attempts, but not suicides, may increase slightly, but the mechanism remains unclear.

It is difficult to study whether antidepressants increase suicidality. Prospective studies of suicidal behavior are impractical, and suicide is so rare that case-control studies require very large numbers of subjects. These researchers examined data from Finnish registries on 15,390 people at high risk for attempting suicide because they had been hospitalized for previous attempts from 1997 to 2003.

The investigators assessed each patient’s antidepressant use in the year before hospitalization, serious suicide attempts in the preceding 5 years, hospitalizations for suicidality, antidepressant use after the index hospitalization, and cause of death where applicable. During follow-up (average, 3.4 years after index hospitalization), 602 patients committed suicide, and 7136 attempted suicide.

Compared with no antidepressant use, use of any antidepressant nonsignificantly reduced risk for suicide (relative risk, 0.91) but significantly increased the risk for nonfatal suicide attempts (RR, 1.64). As to specific medications, only fluoxetine significantly decreased risk for completed suicide (RR, 0.52; 95% confidence interval, 0.30–0.93); venlafaxine slightly but significantly increased the risk (RR, 1.61; 95% CI, 1.01–2.57). Antidepressant use significantly reduced mortality from all causes (RR, 0.64). SSRIs significantly decreased risks for cardiovascular and cerebrovascular deaths (RR, 0.42). Children ages 10 to 19 had slightly higher risks for suicide attempts with all antidepressants, including SSRIs, than did the entire group.

Comment: In analyzing the impact of a large number of risk factors at the same time, the authors did not correct for multiple comparisons, making the significance of the results less certain. Even ignoring this issue, results were barely significant in most cases: Confidence intervals overlapped or came close to 1.0. Increased suicide risks may be associated with venlafaxine, because this agent is often given to more severely depressed patients. SSRIs may have reduced cardiovascular and cerebrovascular risk via antiplatelet actions or, perhaps, via interactions with nonpsychiatric medications. Overall, the results do not tell us whether depression undertreatment or the antidepressant itself leads patients to attempt suicide, at least soon after starting medication.

— Steven Dubovsky, MD

Published in Journal Watch Psychiatry January 29, 2007

Citation(s):

Tiihonen J et al. Antidepressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort. Arch Gen Psychiatry 2006 Dec; 63:1358-67.

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