A randomized controlled trial of venlafaxine XR for major depressive disorder after spinal cord injury: Methods and lessons learned

Abstract

Context/objective

We describe the rationale, design, methods, and lessons learned conducting a treatment trial for major depressive disorder (MDD) or dysthymia in people with spinal cord injury (SCI).

Design

A multi-site, double-blind, randomized (1:1) placebo controlled trial of venlafaxine XR for MDD or dysthymia. Subjects were block randomized and stratified by site, lifetime history of substance dependence, and prior history of MDD.

Setting

Six SCI centers throughout the United States.

Participants

Across participating centers, 2536 subjects were screened and 133 were enrolled into the trial. Subjects were 18–64 years old and at least 1 month post-SCI.

Interventions

Twelve-week trial of venlafaxine XR versus placebo using a flexible titration schedule.

Outcome measures

The primary outcome was improvement in depression severity at 12 weeks. The secondary outcome was improvement in pain.

Results

This article includes study methods, modifications prompted by a formative review process, preliminary data on the study sample and lessons learned. We describe common methodological and operational challenges conducting multi-site trials and how we addressed them. Challenges included study organization and decision making, staff training, obtaining human subjects approval, standardization of measurement and treatment, data and safety monitoring, subject screening and recruitment, unblinding and continuity of care, database management, and data analysis.

Conclusions

The methodological and operational challenges we faced and the lessons we learned may provide useful information for researchers who aim to conduct clinical trials, especially in the area of medical treatment of depression in people with SCI.

Keywords:

• Antidepressants
• Dysthymia
• Major depressive disorder
• Pain
• Randomized controlled trials
• Research design
• Spinal cord injuries

Acknowledgements

The study was developed and funded by grants from the National Institute on Disability and Rehabilitation Research, Office of Special Education and Rehabilitative Services, US Department of Education to the University of Washington (H133A060107, H133N060033), University of Alabama, Birmingham (H133A060107), Rehabilitation Institute of Chicago (H133N110014) and the University of Michigan, Ann Arbor (H133N110002). We acknowledge Pfizer for supplying the study drug. We are grateful to Christian Buhagiar, Jason Barber and Youlim Choi for data coordination, data management and analyses, to Jeff Purcell for investigational pharmacy leadership as well as to the PRISMS study team including Jan Troncale and Cheryl McCullumsmith. The opinions contained in this publication are those of the grantees and do not necessarily reflect those of the US Department of Education.