Long-term tolerability and effectiveness of duloxetine in the treatment of major depressive disorder.

To examine the long-term safety, tolerability, and effectiveness of duloxetine in the treatment of major depressive disorder in a naturalistic study design meant to mimic clinical practice. Data were from the long-term, open-label, extension phase that followed a 12-week acute-treatment, multicenter study of adult outpatients with major depressive disorder. After the first week of the acute phase, all patients were treated with at least 60 mg daily duloxetine, which could be titrated to a maximum dose of 120 mg daily. Outcome measures were collected at monthly visits and included spontaneously reported adverse events, weight, vital signs, and the 17-item Hamilton Depression Rating scale. Seventy-two of the 177 (40.7%) patients who entered the extension phase of this study completed the study. The mean duration of participation in the extension was 305 days, with total exposure ranging from 68 to 707 days. Of the 177 patients who entered the extension, only 12 or 13 (7.0%) showed clinically significant worsening of depression that led to study discontinuation. The mean 17-item Hamilton Depression Rating scale score remained below 7 throughout the extension. A total of 21/177 patients (11.9%) discontinued due to adverse events during extension treatment. The adverse events causing discontinuation during the extension, with the exception of weight gain, were generally not unique to the extension phase, with 11/21 patients (52.0%) discontinuing due to adverse events that were first reported during acute treatment. Weight gain was reported as a reason for discontinuation during extension treatment in 4/177 (2.3%) patients. In this open-label study, efficacy was maintained for most patients. The adverse events causing discontinuation during the extension phase were generally not unique to the extension phase. Few patients experienced significant weight gain.