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Urquhart DM, Wluka AE, van Tulder M, et al. Efficacy of Low-Dose Amitriptyline for Chronic Low Back Pain: A Randomized Clinical Trial. JAMA Intern Med. 2018 Nov 1;178(11):1474-1481. doi: 10.1001/jamainternmed.2018.4222.
Area Score
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Special Interest - Pain -- Physician

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; ?2 = 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: Identifier: ACTRN12612000131853.

Comments from MORE raters

General Internal Medicine-Primary Care(US) rater

Great article with a useful design. I appreciated the use of an active comparator to minimize the placebo affect of the TCA. The study, in my mind, is almost more useful for the negative findings (minimal effect on pain at 6 months) rather than the positive findings (potential small benefit on chronic pain).

Special Interest - Pain -- Physician rater

I agree with the Authors' conclusion: it may be worth considering low-dose amitriptyline if the only alternative is an opioid.

Special Interest - Pain -- Physician rater

The authors reported that "participants were contacted by telephone at 2 weeks, 1 to 2 months, 3 months, 4 to 5 months, and 6 months to monitor their progress and any adverse events. The 3- and 6-month outcome questionnaires and the second 3 months of medication were sent to the participants by mail," which is not suitable for VAS.

Special Interest - Pain -- Physician rater

Who uses benztropin in back pain? This comparator isn't a common drug used for this condition, making the findings somewhat questionable.