Duloxetine versus placebo in the treatment of major depressive disorder and associated painful physical symptoms: a replication study

Objective: Painful physical symptoms are common in patients with major depressive disorder (MDD) and can negatively affect patient outcomes. Duloxetine has demonstrated efficacy in treating MDD and other certain painful conditions; this study specifically evaluated patients with both MDD and MDD-associated pain. Methods: This randomized, double-blind clinical trial enrolled adult outpatients with MDD (DSM-IV-TR criteria; Montgomery-Asberg Depression Rating Scale [MADRS] total score >= 20) and at least moderate pain (Brief Pain Inventory, Short Form [BPI] average pain rating >= 3). Patients received placebo (N=266) or duloxetine (N=261) 60 mg once daily (QD) (after starting dose of 30 mg QD for 1 week). This study replicated another study evaluating MDD and MDD-associated pain. Clinical trial registration: Clinicaltrials. gov (NCT01070329). Main outcome measures: Co-primary outcomes were the MADRS total score (change from baseline at 8 week endpoint) and BPI average pain rating (overall main effect over 8 weeks of treatment). The Sheehan Disability Scale (SDS) global functional impairment score at week 8 assessed functioning as a secondary outcome. Changes were analyzed using mixed-effects model repeated measures (MMRM), and the MADRS remission rate (total score <= 12 at 8-week endpoint) was analyzed using the Cochran-Mantel-Haenszel test. Results: Both co-primary objectives and the first two gated secondary objectives were achieved: compared with placebo, duloxetine significantly improved the mean MADRS total score, BPI average pain rating, SDS global functional impairment score, and remission of depression at 8-week endpoint (all p<0.01). The third gated secondary objective, evaluating remission of depression at the last two non-missing visits, was not achieved. The within-group MADRS remission rate was greater for duloxetine-treated patients with >= 50% (versus <50%) improvement in BPI average pain (p<0.001). Safety outcomes were similar to previous reports. This study did not address the effects of duloxetine on MDD and comorbid pain of a known origin. Conclusions: These results replicated findings supporting the efficacy and tolerability of duloxetine compared to placebo as treatment for depression and pain in patients with MDD and at least moderate pain associated with MDD.