This review from the RTI International–University of North Carolina at Chapel Hill Evidence-based Practice Center (EPC) provides a comprehensive summary of the available data addressing the comparative effectiveness of four nonpharmacologic treatments as therapies for patients with treatment-resistant depression (TRD): electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), vagus nerve stimulation (VNS), and cognitive behavioral therapy or interpersonal psychotherapy (CBT or IPT).

The core patient population of interest was patients with major depressive disorder (MDD) who met our definition of TRD: failure to respond following two or more adequate antidepressant treatments. We also included TRD studies in which the patient population could include a “mix” of up to 20 percent of patients with bipolar disorder (i.e., 80 percent or more of patients had only MDD), assuming that this small mix would not substantially alter outcomes seen with MDD-only populations.

Contents

• Preface
• Acknowledgments
• Technical Expert Panel
• Peer Reviewers
• Executive Summary
• Introduction
  • Burden and Costs of Disease
  • Purpose of This Report
  • Scope and Key Questions (KQs)
  • Organization of the Report
• Methods
  • Topic Development
  • Technical Expert Panel
  • Literature Search
  • Study Selection
  • Data Extraction and Analytic Strategy
  • Quality Assessment
  • Applicability Assessment
  • Grading Strength of a Body of Evidence
  • Data Synthesis
  • Peer Review
• Results
  • Introduction
  • Key Question 1 Organization of Results
  • Key Question 1a Nonpharmacologic Interventions—Overview of Head-to-Head Comparisons
  • Key Question 1a Nonpharmacologic Interventions–Key Points of Head-to-Head Comparisons
  • Key Question 1a Nonpharmacologic Interventions—Detailed Analysis of Head-to-Head Comparisons
  • Key Question 1a Nonpharmacologic Interventions—Overview of Active Versus Control Comparisons
  • Key Question 1a Efficacy or Effectiveness of Nonpharmacologic Interventions for Acute Phase Treatment—Key Points of Active Versus Control Comparisons
  • Key Question 1a Efficacy or Effectiveness of Nonpharmacologic Interventions for Acute Phase Treatment—Detailed Analysis of Active Versus Control Comparisons
  • Key Question 1b Comparisons Involving Pharmacologic Interventions for Acute Phase Treatment—Overview of Comparisons
  • Key Question 1b Comparisons Involving Pharmacologic Interventions for Acute Phase Treatment—Overview of Nonpharmacologic Versus Pharmacologic Treatments
  • Key Question 1b Comparisons Involving Pharmacologic Interventions for Acute Phase Treatment—Key Points of Nonpharmacologic Versus Pharmacologic Treatments
  • Key Question 1b Comparisons Involving Pharmacologic Interventions for Acute Phase Treatment—Detailed Analysis of Nonpharmacologic Versus Pharmacologic Treatments
  • Key Question 1b Pharmacologic Interventions for Acute Phase Treatment—Overview of Pharmacologic Versus Pharmacologic Treatments
  • Key Question 1b Pharmacologic Interventions for Acute Phase Treatment—Key Points of Direct Comparisons
  • Key Question 1b Pharmacologic Interventions for Acute Phase Treatment—Detailed Analysis of Direct Comparisons
  • Key Question 2 Efficacy or Effectiveness for Maintaining Remission or Treating Patients With Unresponsive or Recurrent Disease: Overview
  • Key Question 2 Efficacy or Effectiveness for Maintaining Remission or Treating Patients With Unresponsive or Recurrent Disease: Key Points
  • Key Question 2 Efficacy or Effectiveness for Maintaining Remission or Treating Patients With Unresponsive or Recurrent Disease: Detailed Analysis
  • Key Question 3 Efficacy or Effectiveness for Treating Treatment-Resistant Depression for Particular Symptom Subtypes
  • Key Question 4 Organization of Safety, Adverse Events, and Adherence
  • Key Question 4a Cognitive Functioning—Overview
  • Key Question 4a Cognitive Functioning—Key Points
  • Key Question 4a Cognitive Functioning—Detailed Analysis
  • Key Question 4b Specific Adverse Events—Overview
  • Key Question 4b Specific Adverse Events—Key Points
  • Key Question 4b Specific Adverse Events—Detailed Analysis
  • Key Question 4c Tolerability as Measured by Withdrawals due to Adverse Events—Overview
  • Key Question 4c Tolerability as Measured by Withdrawals Due to Adverse Events—Key Points
  • Key Question 4c Tolerability as Measured by Withdrawals Due to Adverse Events—Detailed Analysis
  • Key Question 4d Adherence as Measured by Overall Withdrawals—Overview
  • Key Question 4d Adherence as Measured by Overall Withdrawals—Key Points
  • Key Question 4d Adherence as Measured by Overall Withdrawals—Detailed Analysis
  • Key Question 5 Efficacy and Harms for Selected Populations
  • Key Question 6 Health-Related Outcomes—Overview
  • Key Question 6 Health-Related Outcomes-Key Points
  • Key Question 6 Health-Related Outcomes—Detailed Analysis
• Discussion
  • Background
  • Overview of Main Findings
  • Applicability
  • Limitations of This Review
  • Future Research
  • Conclusion
• References
• Appendixes
  • Appendix A Search Strategy
  • Appendix B Data Abstraction Forms
  • Appendix C Excluded Studies
  • Appendix D Evidence Tables
  • Appendix E Abbreviations and Full Names of Diagnostic Scales and Other Instruments
  • Appendix F Characteristics of Studies With Poor Internal Validity
  • Appendix G Articles by Database Searched
  • Appendix H Studies Recommended for Inclusion by Peer and Public Reviewers

Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services¹, Contract No. 290-02-0016I. Prepared by: RTI International-University of North Carolina (RTI-UNC) Evidence-based Practice Center, Research Triangle Park, North Carolina

Suggested citation:

Gaynes BN, Lux L, Lloyd S, Hansen RA, Gartlehner G, Thieda P, Brode S, Swinson Evans T, Jonas D, Crotty K, Viswanathan M, Lohr KN. Nonpharmacologic Interventions for Treatment-Resistant Depression in Adults. Comparative Effectiveness Review No. 33. (Prepared by RTI International-University of North Carolina (RTI-UNC) Evidence-based Practice Center under Contract No. 290-02-0016I.) AHRQ Publication No. 11-EHC056-EF. Rockville, MD: Agency for Healthcare Research and Quality. September 2011. www.effectivehealthcare.ahrq.gov/reports/final.cfm.

This report is based on research conducted by the RTI International-University of North Carolina (RTI-UNC) Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-02-0016I, TO #2). The findings and conclusions in this document are those of the author(s), who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment.

This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement toos, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products or actions may not be stated or implied.

None of the investigators has any affiliations or financial involvement that conflicts with the material presented in this report.

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