Efficacy, safety, and tolerability of desvenlafaxine 50 mg/day and 100 mg/day in outpatients with major depressive disorder^*

ABSTRACT

Objective: To assess the efficacy, safety, and tolerability of 50- and 100-mg/day doses of desvenlafaxine (administered as desvenlafaxine succinate), a serotonin-norepinephrine reuptake inhibitor, for the treatment of major depressive disorder (MDD).

Research design and methods: Patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) MDD and 17-item Hamilton Rating Scale for Depression (HAM-D₁₇) scores ≥20 were randomly assigned to double-blind placebo or desvenlafaxine treatment (fixed dose of 50 mg/day or 100 mg/day) for 8 weeks. The primary efficacy measure was the HAM-D₁₇. Changes from baseline in HAM-D₁₇ scores were analyzed using analysis of covariance. The final on-therapy evaluation was the primary endpoint for efficacy analyses, using last-observation-carried-forward data.

Main outcomes measures and results: The intent-to-treat population included 447 patients. Desvenlafaxine 50 mg was associated with a significantly greater adjusted mean change from baseline on the HAM-D₁₇ (−11.5) compared with placebo (−9.5, p = 0.018); the 100-mg dose group (−11.0) did not achieve statistical significance (p = 0.065). The 100-mg dose group experienced significant improvements compared with placebo on several secondary efficacy measures, including the 6-item Hamilton Depression Rating Scale (p = 0.038) and the Visual Analog Scale–Pain Intensity total score (p = 0.041). Both desvenlafaxine doses were generally well-tolerated. The most common adverse events (incidence ≥10% in either desvenlafaxine group and twice the rate of placebo) were dry mouth, constipation, insomnia, decreased appetite, hyperhidrosis, and dizziness.

Conclusions: These results demonstrate efficacy, safety, and tolerability of desvenlafaxine 50 mg/day for treating MDD. The significant findings on secondary measures support the efficacy of desvenlafaxine 100 mg, as seen in other trials. Conclusions may be limited by the exclusion of MDD patients with comorbid conditions and the short-term desvenlafaxine treatment duration.

Key words: :

• Desvenlafaxine
• Efficacy
• Major depressive disorder
• Safety

Acknowledgments

Declaration of interest: This clinical trial and analysis were sponsored by Wyeth Research, Collegeville, PA, USA. The authors thank Sherri D. Jones, PharmD and Kathleen M. Dorries, PhD of Advogent, for writing and editorial assistance on this manuscript. ML has equity ownership in ChiMatrix LLC electronic data capture and the Liebowitz Social Anxiety Scale; consults for Avera, Astra Zeneca, Tikvah, Wyeth, and Lilly; licenses software or LSAS for GlaxoSmithKline, Pfizer, Avera, Tikvah, Lilly, Indevus, and Servier; speaks and presents posters for Wyeth; and has clinical trial contracts with Pfizer, GlaxoSmithKline, Astra Zeneca, Forest, Tikvah, Avera, Lilly, Novartis, Sepracor, Horizon, and Johnson & Johnson. ALM, SKP, RG, RT, and KAT are employees of Wyeth Research. Clinical trial registration:, NCT00277823.

Notes

† p < 0.01 desvenlafaxine 50 mg vs. placebo