Research report Duloxetine in the treatment of major depressive disorder: Comparisons of safety and tolerability in male and female patients

Background: While some studies have suggested sex differences in the efficacy of antidepressant medications, there have been few investigations into potential sex differences related to safety and/or tolerability. Pooled data from double-blind, placebo-controlled studies were utilized to assess the safety and tolerability of duloxetine in the treatment of major depressive disorder (MDD) in male and female patients. Methods: Safety data were pooled from seven double-blind, placebo-controlled clinical trials of duloxetine. Patients (aged z 18 years) meeting DSM-IV criteria for MDD received duloxetine (40–120 mg/day, male: N=318, female: N=578) or placebo (male: N=242, female: N=484) for up to 9 weeks. Safety was assessed using discontinuation rates, spontaneously reported treatment-emergent adverse events, changes in vital signs and laboratory analyses. Results: Discontinuation rates due to adverse events among duloxetine-treated patients were 18.6% for males and 13.5% for females. The most common treatment-emergent adverse events in both male and female patients included nausea, headache, dry mouth, diarrhea and constipation. The only event occurring at significantly different rates in male and female patients was nausea (Breslow Day p-value=0.008), and the significant difference was driven by a placebo nausea rate that was almost three times greater in females compared with males. No significant differential sex effects were found for pulse, blood pressure or weight. No laboratory analyte had an incidence of abnormal high or low values that differed significantly between male and female patients. Limitations: This was a post-hoc analysis of pooled data from acute phase clinical trials. Plasma concentrations of duloxetine were not obtained. Adverse event rates were based on spontaneous reports and differential dose–response effects were not evaluated. Conclusions: No evidence of clinically meaningful sex differences in the safety and tolerability of duloxetine were uncovered.