Duloxetine hydrochloride: A new dual-acting medication for the treatment of major depressive disorder

Abstract

Duloxetine hydrochloride has recently been approved by the US Food and Drug Administration for the treatment of major depressive disorder (MDD). Duloxetine is a potent inhibitor of serotonin and norepinephrine reuptake, with weak effects on dopamine reuptake. This article reviews the literature on duloxetine with regard to its pharmacodynamics, pharmacokinetics, clinical efficacy, and tolerability. A comprehensive search of MEDLINE was performed using the terms duloxetine, Cymbalta, and major depressive disorder, with no restriction on year. The Eli Lilly and Company clinical trial registry, and abstracts and posters from recent American Psychiatric Association meetings were also reviewed. Duloxetine exhibits linear, dose-dependent pharmacokinetics across the approved oral dosage range of 40 to 60 mg/d. No dose adjustment appears to be needed based on age. Duloxetine has shown efficacy in reducing depressive symptoms compared with placebo, and duloxetine recipients have shown significant improvements in global functioning compared with placebo (both, P < 0.05). Response and remission rates have been comparable to or greater than those seen with fluoxetine or paroxetine. Duloxetine is generally well tolerated, with nausea, dry mouth, and fatigue being the most common treatment-emergent adverse effects. Cardiovascular adverse effects do not appear to result in sustained blood pressure elevations, QTc-interval prolongation, or other electrocardiographic changes. Based on the available evidence, duloxetine is a well-tolerated and effective treatment for MDD in adults. Randomized head-to-head comparisons against established antidepressants are needed to determine the relative safety and efficacy of duloxetine.