1. JAMA Intern Med. 2018 Nov 1;178(11):1474-1481. doi:

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

Urquhart DM(1), Wluka AE(1), van Tulder M(2), Heritier S(1), Forbes A(1), Fong
C(3), Wang Y(1), Sim MR(1), Gibson SJ(4)(5), Arnold C(6)(7), Cicuttini FM(1).

Author information: 
(1)Department of Epidemiology and Preventive Medicine, School of Public Health
and Preventive Medicine, Monash University, Alfred Hospital, Melbourne,
(2)Department of Health Sciences, Amsterdam Public Health Research Institute,
Faculty of Science, Vrije Universiteit, Amsterdam, the Netherlands.
(3)Eastern Health Clinical School, Faculty of Medicine, Nursing and Health
Sciences, Monash University, Melbourne, Australia.
(4)National Ageing Research Institute, Parkville, Australia.
(5)Caulfield Pain Management and Research Centre, Caulfield, Australia.
(6)Department of Anaesthesia and Perioperative Medicine, Monash University,
Alfred Hospital, Melbourne, Australia.
(7)Department of Medicine, Faculty of Medicine, Nursing and Health Sciences,
Monash University, Victoria, Australia.

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.

DOI: 10.1001/jamainternmed.2018.4222 
PMCID: PMC6248203 [Available on 2019-10-01]
PMID: 30285054