Efficacy and Safety of Duloxetine 60 mg and 120 mg Daily in Patients Hospitalized for Severe Depression: A Double-Blind Randomized Trial

Objective: To assess whether hospitalized patients with severe depression and potential suicidal ideation/behavior have earlier and better response to duloxetine 120 mg daily than 60 mg daily.

Method: Adults from 34 sites in 4 countries with severe major depressive disorder, defined by DSM-IV criteria, who were demonstrating Montgomery-Asberg Depression Rating Scale (MADRS) scores ≥ 30, 6-item Hamilton Depression Rating Scale (HDRS-6) scores ≥ 12, and Clinical Global Impressions-Severity of Illness scale (CGI-S) ≥ 4 and hospitalized ≥ 2 weeks underwent double-blind treatment with either duloxetine 60 mg (n = 167) or 120 mg (n = 171) daily for 8 weeks. Patients treated with 60 mg/d who did not respond had their doses titrated up to 120 mg/d. Primary outcome was the difference in baseline to week 4 change in MADRS scores between the groups. Secondary outcomes were baseline to week 8 changes in MADRS and HDRS-6 scores, response and remission, CGI-S scores, CGI-Improvement scores, Patient Global Impressions-Improvement, Hamilton Anxiety Rating Scale scores, and Reasons For Living inventory results. Safety was also assessed. The study was conducted between February 9, 2007, and August 26, 2008.

Results: There was no significant difference in mean baseline to week 4 MADRS score change between the 60-mg (−20.1) and 120-mg (−19.9) groups (P = .88). At week 4, 96/166 (60 mg) and 106/170 (120mg) patients responded and maintained responses at week 8 by further decreasing mean MADRS scores to 5.8 (60 mg) and 5.6 (120 mg). At week 8, 226/336 (67.3%) patients achieved remission, with no difference demonstrated between groups. Most secondary efficacy measures were significantly reduced from baseline to week 8 within each group and did not differ between groups. Treatment-emergent adverse events observed with > 10% frequency in both groups were headache and nausea.

Conclusions: Duloxetine 60-mg and 120-mg doses were equally effective and demonstrated no significant differences in treating severe depressive symptoms in hospitalized patients. The safety and tolerability profile of duloxetine in both dosages did not differ and was similar to those reported in previous duloxetine studies.

Trial Registration: clinicaltrials.gov Identifier: NCT00422162

J Clin Psychiatry 2011;72(8):1086-1094

Submitted: September 28, 2009; accepted January 28, 2010.

Online ahead of print: September 21, 2010 (doi:10.4088/JCP.09m05723blu).

Corresponding author: Stephan Brecht, MD, PhD, CDep Medical Affairs, Boehringer Ingelheim GmbH, 55216 Ingelheim am Rhein, Ingelheim, Germany ([email protected]).