Duloxetine: A New Treatment for the Emotional and Physical Symptoms of Depression

Abstract

BACKGROUND: Depression is underdiagnosed in the primary care setting. Physical symptoms such as aches, pains, and gastrointestinal disturbance are frequently associated with major depressive disorder (MDD) and are often the presenting symptoms. Duloxetine, a dual-reuptake inhibitor of serotonin and norepinephrine, may have a positive effect on physical symptoms in addition to efficacy in treating emotional symptoms of depression. METHOD: Efficacy was evaluated in 6 double-blind, placebo- and/or active comparator-controlled trials of duloxetine for patients with MDD (DSM-IV criteria). Efficacy in depression was determined primarily using the 17-item Hamilton Rating Scale for Depression (HAM-D-17). Secondary efficacy measures included subscales of the HAM-D-17 and assessment of physical symptoms. Safety evaluations included adverse events, vital signs, laboratory analyses, and electrocardiograms. Safety was evaluated by pooling the data from the MDD trials and a study of duloxetine in nondepressed patients. RESULTS: Duloxetine demonstrated significant differences from placebo on core mood symptoms, physical symptoms (e.g., back pain), and global functioning as early as week 1 of treatment. The estimated probabilities of remission in the studies that demonstrated efficacy ranged from 43% to 57%. The most frequently observed adverse events for duloxetine-treated patients included nausea, dizziness, insomnia, fatigue, and somnolence. Duloxetine did not prolong corrected QT intervals, and the rate of sustained elevations of blood pressure did not differ significantly from placebo. CONCLUSION: In these studies, duloxetine was safe and effective in the treatment of both emotional and physical symptoms of MDD. Based on dose assessments, 60 mg q.d. appears to be the optimum starting and therapeutic dose.

Figure 1.

Mean Change in HAM-D-17 Total Score From Baseline to Endpoint in the 6 Trials of Duloxetine for Major Depressive Disorder (MMRM analysis)^a

Figure 2.

Estimated Probabilities of Remission (MMRM analysis) for All Randomized Patients in Those Studies Showing Superiority of Duloxetine Over Placebo on the Primary Efficacy Measure^a

Figure 3.

Mean Change in (A) HAM-D-17 Item 1 (depressed mood) and (B) HAM-D-17 Core Subfactor From Baseline to Last Visit for Duloxetine vs. Placebo (MMRM analysis)^a

Figure 4.

Estimated Probability of Patients' Demonstrating at Least a 1-Point Improvement in (A) CGI-S Score and (B) PGI-I Score in Study 1^a

Figure 5.

Mean Percentage Improvement in Overall Visual Analogue Scale (VAS) Pain Severity Score in (A) Study 1 and (B) Study 2^a