Background: Depression is a chronic recurring disorder and guidelines recommend long-term therapy. This clinical trial evaluated the long-term (1 year) safety and efficacy of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine, in patients with DSM-IV major depressive disorder.
Method: This was an open-label, 52-week, multinational clinical trial in outpatients (age > or = 18 years) who received duloxetine at 80 mg/day (administered 40 mg twice daily) to 120 mg/day (administered 60 mg twice daily) for up to 1 year.
Results: A total of 1279 patients had postbaseline data. Of these, 520 were exposed to duloxetine for at least 360 days, yielding approximately 808 patient-years of total exposure. Mean changes in Clinical Global Impressions-Severity of Illness scale (CGI-S) score, 17-item Hamilton Rating Scale for Depression total score and subfactor scores, Beck Depression Inventory-II score, and Sheehan Disability Scale score and mean Patient Global Impression-Improvement scale (PGI-I) scores all showed highly significant (p <.001) improvements at all assessment times. The estimated probabilities of improvement in CGI-S and PGI-I scores at week 1 were 40.4% and 59.2%, respectively, and at week 2 were 70.0% and 78.3%. The estimated probabilities of remission at weeks 6, 28, and 52 were 50.8%, 75.6%, and 81.8%, respectively. Adverse events led to discontinuation in 218 patients (17.0%). The most frequent specific events leading to discontinuation were nausea (1.5%), somnolence (1.4%), vomiting (0.9%), hypomania (0.8%), pregnancy (0.8%), dizziness (0.6%), insomnia (0.6%), and hypertension (0.5%). Treatment-emergent adverse events that were reported by > 10% of patients included nausea, insomnia, headache, somnolence, dry mouth, dizziness, constipation, sweating increase, anxiety, diarrhea, and fatigue. Most events occurred early in the study. Of those events that first occurred or worsened after discontinuation, only dizziness (8.3%) occurred in more than 5% of patients. Mean changes from baseline to last observation for standing and supine pulse were less than 2 b.p.m. Mean changes in blood pressure (< 1.0 mm Hg), corrected QT interval (< 1 msec), and body weight (2.4 kg [5.3 lb]) were not clinically significant. Laboratory analyses varied across visits, and mean changes after 52 weeks were generally close to zero. The incidence of laboratory values above or below normal limits at any time during treatment was low.
Conclusion: Duloxetine was effective, safe, and well tolerated in the long-term treatment of major depression at a dose of 80 to 120 mg/day in this study.