Background: Duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, was evaluated for therapeutic efficacy and safety/tolerability in the treatment of major depression.
Method: In an 8-week multicenter, double-blind, placebo-controlled study, 173 patients (aged 18-65 years) with DSM-IV major depressive disorder were randomly allocated to receive placebo (N = 70), duloxetine (N = 70), or fluoxetine, 20 mg q.d. (N = 33). Duloxetine dose was titrated in the first 3 weeks in a forced-titration regimen from 40 mg (20 mg b.i.d.) to 120 mg/day (60 mg b.i.d.). Patients were required to have a Clinical Global Impressions (CGI)-Severity of Illness scale score of at least moderate severity (> or = 4) and a 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score of at least 15. Patients could not have had any current primary DSM-IV Axis I diagnosis other than major depressive disorder, or any anxiety disorder as a primary diagnosis within the past year, excluding specific phobias. The primary efficacy measurement was the HAM-D-17 total score, and secondary measures included the Montgomery-Asberg Depression Rating Scale, CGI-Severity of Illness and CGI-Improvement, and Patient Global Impression of Improvement. Safety was evaluated by recording the occurrence of discontinuation rates and treatment-emergent adverse events and by measurement of vital signs and laboratory analytes.
Results: Duloxetine was superior to placebo in change on the HAM-D-17 (p = .009). Estimated probabilities of response and remission were 64% and 56%, respectively, for duloxetine, compared with 52% and 30% for fluoxetine and 48% and 32% for placebo. Duloxetine was numerically superior to fluoxetine on the primary and most of the secondary outcome measures. In general, duloxetine was well tolerated; 76% of patients achieved the maximum dose, and insomnia and asthenia were the only adverse events reported statistically significantly (p < .05) more frequently by duloxetine-treated patients compared with placebo-treated patients.
Conclusion: These data indicate that duloxetine is efficacious for the treatment of major depressive disorder and is well tolerated and safe.