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Objective: The authors explored the relationship between the initiation of therapy with selective serotonin reuptake inhibitor (SSRI) antidepressants and completed suicide in older patients. Method: The authors linked population-based coroner’s records with patient-level prescription data, physician billing claims, and hospitalization data for more than 1.2 million Ontario residents 66 years of age and older from 1992 to 2000. For each suicide case, four closely matched comparison subjects were selected using propensity score methods. The authors determined the odds ratio for suicide with SSRIs versus other antidepressant treatment, calculated at discrete monthly intervals from the start of treatment. Results: Of 1,329 suicide cases, 1,138 (86%) were each fully matched to four comparison subjects using propensity scores. During the first month of therapy, SSRI antidepressants were associated with a nearly fivefold higher risk of completed suicide than other antidepressants (adjusted odds ratio: 4.8, 95% confidence interval=1.9–12.2). The risk was independent of a recent diagnosis of depression or the receipt of psychiatric care, and suicides of a violent nature were distinctly more common during SSRI therapy. Numerous sensitivity analyses revealed consistent results. No disproportionate suicide risk was seen during the second and subsequent months of treatment with SSRI antidepressants, and the absolute risk of suicide with all antidepressants was low. Conclusions: Initiation of SSRI therapy is associated with an increased risk of suicide during the first month of therapy compared with other antidepressants. The absolute risk is low, suggesting that an idiosyncratic response to these agents may provoke suicide in a vulnerable subgroup of patients.