Duloxetine for the Treatment of Major Depressive Disorder

Background. Existing therapies for depression frequently fail to provide full remission. This report evaluates the efficacy and safety of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine, in the treatment of major depressive disorder (MDD). Method. Efficacy of duloxetine was evaluated in six double-blind, placebo- and/or active-comparator-controlled clinical trials. A study of duloxetine in patients with stress urinary incontinence was also included in the safety assessments. The primary efficacy measure was total score on the 17-item Hamilton Rating Scale for Depression (HAMD-17). Secondary measures included estimated probabilities of response and remission, and changes in the Clinical Global Impressions scale, Patients Global Impression scale, and the Hamilton Rating Scale for Anxiety. Physical symptoms were assessed using Visual Analog Scales for Pain. Safety evaluations included reporting of adverse events, changes in vital signs, electrocardiogram, blood pressure, and laboratory analyses. Results. Duloxetine was significantly superior to placebo in reducing mean HAMD-17 total score in four of the six studies. Significant improvements for duloxetine over placebo were also observed on many secondary efficacy measures across five of the studies. Probabilities of remission >55% were observed in two of the studies, while in a third study the probability of remission with duloxetine treatment was nearly three times that observed with placebo (44% versus 16%). Duloxetine also produced significant improvement in painful physical symptoms compared with placebo, in many cases after only 2 weeks of treatment. The discontinuation rate due to adverse events (14.6%) was similar to those observed with selective serotonin reuptake inhibitors. The most frequently reported adverse events were nausea, dry mouth, fatigue, and insomnia. Conclusion. Duloxetine was demonstrated to be safe and effective in the treatment of MDD. The starting dose with the best balance of efficacy and tolerability is 60 mg per day. Psychopharmacology Bulletin. 2002;36(4):106-132