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Emerging Perspectives: Look Again — SSRIs and Fewer Suicide Attempts

Feature |
July 13, 2007

Emerging Perspectives: Look Again — SSRIs and Fewer Suicide Attempts

  1. Joel Yager, MD

In particular patients, SSRIs might increase suicidality, but overall they are associated with significant decreases in suicide attempts.

  1. Joel Yager, MD

Several epidemiological studies from the past two decades have associated the prescription of SSRIs with lower U.S. suicide rates. More recently, a flurry of articles indicated that 1% to 3% of depressed patients under age 25 treated with SSRIs and new-generation non-SSRI antidepressants experienced suicidality (predominantly, suicidal ideation; occasionally, attempts; but not completed suicides). With these newer studies came enormous media attention, a black-box warning from the FDA in 2004, considerable consternation among parents and patients, fewer prescriptions for these medications, and a subsequent 2004 bump in suicide rates for young patients. Three new articles suggest that antidepressant medications do not increase rates of suicide attempts and completed suicides and, indeed, that treated patients have substantially lower attempt rates.

Simon and Savarino used outpatient claims data from a prepaid health plan to examine definite or possible suicide attempts reported from 90 days before starting treatment to 180 days after the initiation of treatment. There were 70,368 depressed patients receiving antidepressant medications from primary care physicians, 7,297 receiving antidepressants from psychiatrists, and 54,123 who had an initial psychotherapy visit. The data showed 618 definite and 97 possible suicide attempts. Attempt rates were highest in adolescents and young adults and were highest in the month before treatment initiation, next highest in the month after treatment initiation, and lower thereafter. Consistent with typical referral patterns, attempt rates were highest for psychiatric patients, intermediate for psychotherapy patients, and lowest for primary care patients. These patterns held for a subgroup of 23,910 patients under age 25.

Gibbons et al. compared suicide attempt rates before and after initiation of treatment with an SSRI, a non-SSRI antidepressant (bupropion, mirtazapine, nefazodone, or venlafaxine), or a tricyclic antidepressant. Subjects were 226,866 veterans with depression newly diagnosed in 2003 or 2004. For those receiving SSRIs or new-generation non-SSRIs, attempt rates were lower after treatment (average observation period, about 14 months) than before treatment (average observation period, about 10 months). After treatment initiation, attempt rates among SSRI recipients were about one third of the rates among patients receiving a non-SSRI, a tricyclic, or no antidepressant. Adjusted for patient-months, the relative risk for suicide attempts after, versus before, treatment initiation was 0.383 for SSRIs, 0.397 for non-SSRIs, and 0.505 for tricyclics. Patients receiving SSRI monotherapy had significantly less risk than those receiving no antidepressant.

Finally, Posner et al. employed a rigorous method of categorizing “suicidal adverse events” to reexamine data (including 427 reports of adverse events) from the 25 pediatric antidepressant clinical trials that the FDA used in its determinations. The categories were completed suicides, suicide attempts, preparation for suicide, suicidal ideation, self-injurious behaviors without suicidal intent, self-injurious behaviors with unknown intention, events without deliberate self-harm, and indeterminate events. The investigators identified 26 additional possible suicidal events and eliminated 12 others, and their methods classified 50% fewer events as suicide attempts than did the original researchers’ methods.

Comment

The first two studies affirm the association between treatment and reduction in suicide attempts, and the third reinterprets findings reported by pharmaceutical companies to the FDA, concluding that they contained only half as many actual suicide attempts as previously thought. On balance, these results strongly support the use of antidepressant medications for patients with depression. An editorialist states that “it is much more likely that suicidal behavior leads to treatment than that treatment leads to suicidal behavior.” Nevertheless, these association studies do not preclude the possibility that a minority of younger patients experience increased suicidal ideation and perturbation when they start antidepressant medications. Patients deserve close follow-up during treatment initiation.

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