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Efficacy of Low-Dose Amitriptyline for Chronic Low Back PainA Randomized Clinical Trial

Educational Objective
To examine the efficacy of a low-dose antidepressant compared with an active comparator in reducing pain, disability, and work absence and hindrance in individuals with chronic low back pain (LBP).
1 Credit CME
Key Points

Question  Is a low-dose tricyclic antidepressant effective in the treatment of chronic low back pain?

Findings  In this randomized clinical trial of 146 participants with chronic low back pain, the use of low-dose amitriptyline did not demonstrate an improvement in pain, disability, or work at 6 months compared with an active comparator. However, there was a reduction in disability at 3 months, an improvement in pain intensity that was nonsignificant at 6 months, and minimal adverse events reported for the treatment group.

Meaning  These results suggest that low-dose amitriptyline may be an effective treatment for chronic low back pain; although large-scale trials are needed, it may be worth considering amitriptyline, especially if the alternative is opioids.


Importance  Antidepressants at low dose are commonly prescribed for the management of chronic low back pain and their use is recommended in international clinical guidelines. However, there is no evidence for their efficacy.

Objective  To examine the efficacy of a low-dose antidepressant compared with an active comparator in reducing pain, disability, and work absence and hindrance in individuals with chronic low back pain.

Design, Setting, and Participants  A double-blind, randomized clinical trial with a 6-month follow-up of adults with chronic, nonspecific, low back pain who were recruited through hospital/medical clinics and advertising was carried out.

Intervention  Low-dose amitriptyline (25 mg/d) or an active comparator (benztropine mesylate, 1 mg/d) for 6 months.

Main Outcomes and Measures  The primary outcome was pain intensity measured at 3 and 6 months using the visual analog scale and Descriptor Differential Scale. Secondary outcomes included disability assessed using the Roland Morris Disability Questionnaire and work absence and hindrance assessed using the Short Form Health and Labour Questionnaire.

Results  Of the 146 randomized participants (90 [61.6%] male; mean [SD] age, 54.8 [13.7] years), 118 (81%) completed 6-month follow-up. Treatment with low-dose amitriptyline did not result in greater pain reduction than the comparator at 6 (adjusted difference, −7.81; 95% CI, −15.7 to 0.10) or 3 months (adjusted difference, −1.05; 95% CI, −7.87 to 5.78), independent of baseline pain. There was no statistically significant difference in disability between the groups at 6 months (adjusted difference, −0.98; 95% CI, −2.42 to 0.46); however, there was a statistically significant improvement in disability for the low-dose amitriptyline group at 3 months (adjusted difference, −1.62; 95% CI, −2.88 to −0.36). There were no differences between the groups in work outcomes at 6 months (adjusted difference, absence: 1.51; 95% CI, 0.43-5.38; hindrance: 0.53; 95% CI, 0.19-1.51), or 3 months (adjusted difference, absence: 0.86; 95% CI, 0.32-2.31; hindrance: 0.78; 95% CI, 0.29-2.08), or in the number of participants who withdrew owing to adverse events (9 [12%] in each group; χ2 = 0.004; P = .95).

Conclusions and Relevance  This trial suggests that amitriptyline may be an effective treatment for chronic low back pain. There were no significant improvements in outcomes at 6 months, but there was a reduction in disability at 3 months, an improvement in pain intensity that was nonsignificant at 6 months, and minimal adverse events reported with a low-dose, modest sample size and active comparator. Although large-scale clinical trials that include dose escalation are needed, it may be worth considering low-dose amitriptyline if the only alternative is an opioid.

Trial Registration  anzctr.org.au Identifier: ACTRN12612000131853

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Article Information

Accepted for Publication: July 4, 2018.

Correction: This article was corrected on March 4, 2019, to fix errors in the y-axis of Figure 2B.

Corresponding Author: Donna M. Urquhart, PhD, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Victoria 3004, Australia (donna.urquhart@monash.edu).

Published Online: October 1, 2018. doi:10.1001/jamainternmed.2018.4222

Author Contributions: Drs Urquhart and Cicuttini had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Urquhart, Wluka, van Tulder, Sim, Gibson, Arnold, Cicuttini.

Acquisition, analysis, or interpretation of data: Urquhart, Wluka, van Tulder, Heritier, Forbes, Fong, Wang, Cicuttini.

Drafting of the manuscript: Urquhart, Heritier, Forbes, Cicuttini.

Critical revision of the manuscript for important intellectual content: Urquhart, Wluka, van Tulder, Forbes, Fong, Wang, Sim, Gibson, Arnold, Cicuttini.

Statistical analysis: Urquhart, van Tulder, Heritier, Forbes, Wang, Cicuttini.

Obtained funding: Urquhart, Wluka, Sim, Gibson, Cicuttini.

Administrative, technical, or material support: Urquhart, Wluka, Sim, Cicuttini.

Supervision: Urquhart, Wluka, Fong, Gibson, Arnold, Cicuttini.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported by the National Health and Medical Research Council (NHMRC, Australia, ID 1024401). Drs Urquhart, Wluka, and Wang are recipients of NHMRC Career Development Fellowships (Clinical Level 1 No. 1011975; Clinical Level 2 No. 1063574; Clinical Level 1 No. 1065464, respectively).

Role of the Funder/Sponsor: The NHMRC had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank the study participants. We also thank our study personnel, including Judy Hankin, BA, RN (study coordination, participant recruitment, outcome data collection), Alice Noone, BAppSc (study coordination, participant recruitment, outcome data collection), Molly Bond, BBiotech (study coordination, participant recruitment, outcome data collection), Cameron Redpath, BBNsc (participant recruitment, outcome data collection), Clare Bellhouse, BA, MPsych (participant recruitment, outcome data collection), Pyae Phyo Maung, MBBS, MPH (participant recruitment, outcome data collection), Waruna Peiris, BBiomedSc, (data entry and cleaning), Shane Anthony, MBBS (data entry and cleaning), Muhammad Hasim, MBBS (identification and referral of potential participants), who were involved in the coordination and execution of this study. They are affiliated with Monash University, Alfred Health and/or Eastern Health, Melbourne Australia. They were not financially compensated outside of salary.

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