A randomized placebo-controlled trial of duloxetine in patients with major depressive disorder and associated painful physical symptoms

Abstract

Objective:

Painful physical symptoms are common in patients with major depressive disorder (MDD) and may predict poorer treatment outcomes. Duloxetine has demonstrated efficacy in treating both MDD and certain other painful conditions. This randomized, double-blind clinical trial assessed the effects of duloxetine in patients with both MDD and MDD-associated physical pain.

Methods:

Participants were outpatient adults with current MDD (DSM-IV-TR criteria; Montgomery–Åsberg Depression Rating Scale [MADRS] total score ≥20) and at least moderate pain (Brief Pain Inventory Short Form [BPI] average pain rating ≥3) and with at least one prior episode of MDD. Patients received placebo (N = 266) or duloxetine (N = 262) 60 mg once daily. This trial is registered at clinicaltrials.gov (NCT01000805).

Main outcome measures:

Coprimary outcomes were MADRS total score (change from baseline at 8 weeks) and BPI average pain rating (overall main effect over 8 weeks). The Sheehan Disability Scale (SDS) global functional impairment score (change from baseline at 8 weeks) was used to assess functioning. Remission was defined as MADRS total score ≤12 at the 8-week endpoint. Changes were analyzed using mixed-effects model repeated measures (MMRM).

Results:

Compared with placebo, duloxetine significantly improved the mean MADRS total score, BPI average pain rating, and SDS global functional impairment score (all p ≤ 0.05 for analyses described above). The remission rate was significantly greater with duloxetine compared with placebo (p = 0.001) and was greater for duloxetine-treated patients with ≥50% versus <50% improvement in BPI average pain score (p ≤ 0.001). Treatment emergent adverse events that occurred in at least 5% of duloxetine-treated patients and at twice the rate of placebo included nausea, somnolence, constipation, decreased appetite, and hyperhidrosis. Rates of discontinuation due to adverse events were greater for duloxetine than placebo (8.0% vs 3.4%, respectively; p = 0.024). This study did not address the effects of duloxetine on MDD and comorbid pain of a known origin.

Conclusions:

These results support the efficacy and tolerability of duloxetine in the treatment of depression and associated painful physical symptoms in patients with MDD and at least moderate MDD-associated pain.

Key words::

• Duloxetine
• Major depressive disorder
• Pain
• Randomized clinical trial

Transparency

Declaration of funding

Funding was provided by Eli Lilly and Company; Eli Lilly was involved in study design, analysis and interpretation of data, writing of the report, and the decision to submit the paper for publication.

Declaration of financial/other relationships

P.J.G., J.M.M., M.J.R., and L.B.M. are employees and stock holders of Eli Lilly and Company. M.G. and W.Z. are former employees of Lilly USA LLC.

Acknowledgements

Assistance in preparing the manuscript was provided by Thomas Melby, i3 Statprobe, USA, under contract with Eli Lilly and Company.

These findings were presented in part at the 164th Annual Meeting of the American Psychiatric Association, May 14–18, 2011, Honolulu, Hawaii.