Time course of improvement of different symptom clusters in patients with major depression and pain treated with duloxetine or placebo

Abstract

Objective:

This post hoc analysis assessed improvements in a broad range of psychopathological dimensions and in interference of pain with functioning as well as the time course of these improvements in patients with major depressive disorder (MDD) and pain treated with duloxetine versus placebo.

Research design and methods:

Data were derived from an 8-week, double-blind, placebo-controlled study in adult outpatients with MDD and non-specific physical pain. Mean times between improvement in Brief Pain Inventory (BPI) pain severity and interference of pain with functioning, depression severity, and dimensions of the Symptom Checklist-90 Revised (SCL-90-R) subscales were evaluated by responder analysis.

Results:

For all SCL-90-R subscores, a higher percentage of duloxetine-treated patients reached responder status (50% improvement) as compared to placebo, of these anger/hostility and interpersonal sensitivity had the highest response rates. In the duloxetine-treated group, response for anger/hostility, phobic anxiety, psychoticism, and most items assessing interference of pain with functioning was reached earlier than response for pain severity. The times to response for Montgomery–Asberg Depression Rating Scale (MADRS) and for pain severity were similar. In the placebo-treated group, times to response for depression, anxiety, and MADRS were longer than response for pain severity.

Conclusions:

Duloxetine, and to a lesser degree placebo, not only improved depressive symptomatology and pain severity but also a much broader range of psychopathological symptoms. Time courses of improvements were different for duloxetine and placebo, in that depression and interference of pain with functioning improved earlier than pain severity in duloxetine-treated patients but not in placebo-treated patients. These results suggest that time to response is a valuable means of characterizing treatment effects.

Limitations:

Pain was only assessed as a symptom and no further clinical diagnosis for pain syndromes were performed.

Clinical trial registry ID:

www.clinicaltrial.gov - NCT00191919

Key words::

• Duloxetine
• Depression
• Pain
• Symptom cluster
• Time course

Transparency

Declaration of funding

This study was sponsored by Eli Lilly and Company, Indianapolis, IN, USA, and Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany.

Declaration of financial/other relationships

K.D. has served on the advisory boards of Boehringer Ingelheim GmbH and Eli Lilly and Company and received honoraria for his services. D.D. is an employee of Eli Lilly and Company, Indianapolis, IN, USA, and holds company stock. C.P. is an employee of Boehringer Ingelheim Pharma Inc., Ridgefield, CT, USA; J.C. is an employee of Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany; and S.B. is an employee of Boehringer Ingelheim GmbH, Ingelheim, Germany. CMRO peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors accept full responsibility for conducting and accessing data from the study. All authors participated in the decision to publish the data. The authors wish to thank all the investigators and patients for their participation in the study. The authors acknowledge the medical writing assistance provided by Dr G.V. Reddy, PRIMO Scientific Corporation, Panama City, Republic of Panama.