What happens with adverse events during 6 months of treatment with selective serotonin reuptake inhibitors?

Objective: Although adverse events are a key factor in compliance, their evolution during treatment with antidepressants is poorly documented. Therefore, the time course of adverse events during 6 months of antidepressant treatment was investigated. Method: 85 psychiatric outpatients with a DSM-IV diagnosis of major depressive disorder (with the exclusion of other DSM-IV Axis I disorders) were enrolled between September 2002 and March 2003 in a multicenter, randomized, double-blind trial with selective serotonin reuptake inhibitors (fluoxetine [N = 421 and paroxetine [N = 43]). At each visit, the presence and severity of treatment-emergent adverse events were assessed systematically using the UKU Side Effect Rating Scale (UKU). General linear mixed modeling was used to investigate the predictors of the time course of adverse events. Results: Overall, the number of at least moderately severe adverse events decreased with time. More severely depressed patients reported overall more (at least moderately severe) adverse events than less severely depressed patients (p =.0002), but the decrease in reported adverse events was comparable over time. Men (N = 30) and women (N = 55) reported initially the same number of at least moderately severe adverse events, but the habituation was more rapid in men (p <.0001). Completers (N = 58) and dropouts (N = 27) did not differ initially, but completers' habituation was more rapid (p =.014). The habituation of adverse events was also more rapid in recurrent than in first-episode patients but only in men (p =.0025). Conclusion: The time course of adverse events varies with the severity of depression, sex, completer or dropout status, and recurrent versus first-episode depression.