Low-Dose Amitriptyline Effective for Chronic Low Back Pain

Laurie Barclay, MD


January 02, 2019

Efficacy of Low-Dose Amitriptyline for Chronic Low Back Pain: A Randomized Clinical Trial

Urquhart DM, Wluka AE, van Tulder M, et al
JAMA Intern Med. 2018;178:1474-1481

Study Summary

The largest contributor to global disability is low back pain, for which various treatments are available but are of limited efficacy. International clinical guidelines recommend low-dose antidepressants for management of chronic low back pain, and these are often prescribed for this widespread condition. To date, however, there has been no evidence that they are effective for this indication.

The goal of this double-blind, randomized clinical trial was to compare the efficacy of 6 months of treatment with a low-dose antidepressant (amitriptyline, 25 mg/day) versus an active comparator (benztropine mesylate, 1 mg/day) in reducing pain, disability, and work absence and interference in adults with chronic, nonspecific low back pain.

Participants (n = 146; mean age, 54.8 ± 13.7 years; 61.6% male) were recruited from hospital/medical clinics and through advertising. Pain intensity at 3 and 6 months was measured with the visual analogue scale, and the Descriptor Differential Scale was the primary outcome. The Roland Morris Disability Questionnaire and the Short Form-Health and Labour Questionnaire were used to determine secondary outcomes of disability and work absence and interference.

Among 118 participants (81%) who completed 6-month follow-up, pain reduction with low-dose amitriptyline or the comparator did not differ significantly at 6 months (adjusted difference, -7.81; 95% confidence interval [CI], -15.7 to 0.10) or at 3 months (-1.05; 95% CI, -7.87 to 5.78), independent of baseline pain. The low-dose amitriptyline group versus the comparator group had a statistically significantly better improvement in disability at 3 months (adjusted difference, -1.62; 95% CI, -2.88 to -0.36), but not at 6 months (-0.98; 95% CI, -2.42 to 0.46). Work outcomes of absence or hindrance at 6 months or 3 months and the number of participants who withdrew because of adverse events (12%) did not differ significantly between the groups.


This trial is limited by the heterogeneity of patients with chronic, nonspecific low back pain and its possibly insufficient power to detect differences in work or additional outcomes. Nonetheless, this first double-blind, randomized controlled trial of a low-dose tricyclic antidepressant for this condition suggests that it may be effective. Compared with an active agent, low-dose amitriptyline was associated with a reduction in disability at 3 months and a nonsignificant improvement in pain intensity at 6 months. The two treatments appeared to be equally well tolerated and effective for pain relief.

The findings merit further testing in large-scale randomized trials that include dose escalation. Given the global opioid overuse epidemic, clinicians may find it useful to consider low-dose amitriptyline while awaiting these results, particularly if the only alternative is opioids.

Low-dose amitriptyline has been shown to be effective in other pain conditions, and its off-label prescription for low back pain is rapidly increasing. Because low back pain management focuses on progressively increasing activity levels, low-dose amitriptyline may be relevant to overall therapy by reducing pain, disability, and fear, which are important barriers to activity.



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