Joseph W. Frank, MD, MPH; Travis I. Lovejoy, PhD, MPH; William C. Becker, MD; Benjamin J. Morasco, PhD; Christopher J. Koenig, PhD; Lilian Hoffecker, PhD, MLS; Hannah R. Dischinger, BS; Steven K. Dobscha, MD; Erin E. Krebs, MD, MPH
Presented in part at the Society of General Internal Medicine Annual Meeting, Hollywood, Florida, 11 May 2016.
Note: Everyone who contributed significantly to this study has been listed as an author. The authors had access to all of the study data, take full responsibility for the accuracy of the data analysis, and had authority over preparation of the manuscript and the decision to submit it for publication. All authors approve the manuscript and agree to adhere to all terms outlined in the Annals of Internal Medicine information for authors.
Disclaimer: The views expressed in this article are those of the authors and do not necessarily represent the views of the U.S. Department of Veterans Affairs.
Financial Support: The project was supported by Locally Initiated Project Award QLP 59-046 (principal investigator: Dr. Frank) from the U.S. Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, Substance Use Disorder Quality Enhancement Research Initiative. Dr. Frank received additional support from Career Development Award IK2HX001914 from the U.S. Department of Veterans Affairs, Health Services Research and Development Service. Dr. Lovejoy received support from VA Career Development Award IK2HX001516. Dr. Becker received support from U.S. Department of Veterans Affairs, Health Services Research and Development QUE15-460.
Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-0598.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Registered at PROSPERO (CRD42015020347). Statistical code: Not applicable. Data set: See the tables, figures, and appendix tables.
Requests for Single Reprints: Joseph W. Frank, MD, MPH, VA Eastern Colorado Health Care System, 1055 Clermont Street, Denver, CO 80220; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Frank: VA Eastern Colorado Health Care System, 1055 Clermont Street, Denver, CO 80220.
Dr. Lovejoy: Center to Improve Veteran Involvement in Care, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Road, Mail Code R&D 66, Portland, OR 97239.
Dr. Becker: VA Connecticut Healthcare System, 950 Campbell Avenue, Mail Stop 151B, West Haven, CT 06516.
Dr. Morasco: Center to Improve Veteran Involvement in Care, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Road, Mail Code R&D 99, Portland, OR 97239.
Dr. Koenig: Department of Communication Studies, San Francisco State University, 1600 Holloway Avenue, Humanities Building, Room 282, San Francisco, CA 94132.
Dr. Hoffecker: Health Sciences Library, University of Colorado, 12950 East Montview Boulevard, MS-A003, Aurora, CO 80045.
Ms. Dischinger: Oregon Health & Science University School of Medicine, 3181 SW Sam Jackson Park Road, Portland, OR 97239.
Dr. Dobscha: Center to Improve Veteran Involvement in Care, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Road, Portland, OR 97239.
Dr. Krebs: Center for Chronic Disease Outcomes Research, Minneapolis Veterans Affairs Health Care System, One Veterans Drive, Minneapolis, MN 55417.
Author Contributions: Conception and design: J.W. Frank, T.I. Lovejoy, W.C. Becker, B.J. Morasco, S.K. Dobscha, E.E. Krebs.
Analysis and interpretation of the data: J.W. Frank, T.I. Lovejoy, W.C. Becker, B.J. Morasco, C.J. Koenig, H.R. Dischinger, S.K. Dobscha, E.E. Krebs.
Drafting of the article: J.W. Frank, T.I. Lovejoy, W.C. Becker, B.J. Morasco, C.J. Koenig, L. Hoffecker, H.R. Dischinger, S.K. Dobscha, E.E. Krebs.
Critical revision of the article for important intellectual content: J.W. Frank, T.I. Lovejoy, W.C. Becker, B.J. Morasco, C.J. Koenig, L. Hoffecker, H.R. Dischinger, S.K. Dobscha, E.E. Krebs.
Final approval of the article: J.W. Frank, T.I. Lovejoy, W.C. Becker, B.J. Morasco, C.J. Koenig, L. Hoffecker, H.R. Dischinger, S.K. Dobscha, E.E. Krebs.
Obtaining of funding: J.W. Frank, T.I. Lovejoy, W.C. Becker, B.J. Morasco, S.K. Dobscha, E.E. Krebs.
Administrative, technical, or logistic support: H.R. Dischinger.
Collection and assembly of data: J.W. Frank, W.C. Becker, B.J. Morasco, L. Hoffecker, H.R. Dischinger.
Expert guidelines recommend reducing or discontinuing long-term opioid therapy (LTOT) when risks outweigh benefits, but evidence on the effect of dose reduction on patient outcomes has not been systematically reviewed.
To synthesize studies of the effectiveness of strategies to reduce or discontinue LTOT and patient outcomes after dose reduction among adults prescribed LTOT for chronic pain.
MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library from inception through April 2017; reference lists; and expert contacts.
Original research published in English that addressed dose reduction or discontinuation of LTOT for chronic pain.
Two independent reviewers extracted data and assessed study quality using the U.S. Preventive Services Task Force quality rating criteria. All authors assessed evidence quality using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Prespecified patient outcomes were pain severity, function, quality of life, opioid withdrawal symptoms, substance use, and adverse events.
Sixty-seven studies (11 randomized trials and 56 observational studies) examining 8 intervention categories, including interdisciplinary pain programs, buprenorphine-assisted dose reduction, and behavioral interventions, were found. Study quality was good for 3 studies, fair for 13 studies, and poor for 51 studies. Many studies reported dose reduction, but rates of opioid discontinuation ranged widely across interventions and the overall quality of evidence was very low. Among 40 studies examining patient outcomes after dose reduction (very low overall quality of evidence), improvement was reported in pain severity (8 of 8 fair-quality studies), function (5 of 5 fair-quality studies), and quality of life (3 of 3 fair-quality studies).
Heterogeneous interventions and outcome measures; poor-quality studies with uncontrolled designs.
Very low quality evidence suggests that several types of interventions may be effective to reduce or discontinue LTOT and that pain, function, and quality of life may improve with opioid dose reduction.
Veterans Health Administration. (PROSPERO: CRD42015020347)
Appendix Table 1. Ovid MEDLINE Search Strategy
Appendix Table 2. USPSTF Quality Rating Criteria for RCTs and Cohort Studies
Appendix Table 3. GRADE Criteria for Assessing Quality of Evidence*
Table 1. Effectiveness of Strategies to Reduce or Discontinue LTOT (n = 67 studies)
Study flow diagram.
Table 2. Summary of Findings and Quality-of-Evidence Assessment
Appendix Table 4. Derivation of GRADE Score*
Table 3. Studies of Effect of Dose Reduction or Discontinuation of LTOT on Patient Outcomes (n = 40 studies)
Table 4. Implications for Clinicians and Next Steps for Research
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In this video, Joseph W. Frank, MD, MPH, offers additional insight into the article, "Patient Outcomes in Dose Reduction or Discontinuation of Long-Term Opioid Therapy. A Systematic Review."
Frank JW, Lovejoy TI, Becker WC, et al. Patient Outcomes in Dose Reduction or Discontinuation of Long-Term Opioid Therapy: A Systematic Review. Ann Intern Med. 2017;167:181–191. [Epub ahead of print 11 July 2017]. doi: https://doi.org/10.7326/M17-0598
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Published: Ann Intern Med. 2017;167(3):181-191.
Published at www.annals.org on 11 July 2017
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