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Comment & Response
March 2019

Low-Dose Amitriptyline for Chronic Low Back Pain

Author Affiliations
  • 1Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh
JAMA Intern Med. 2019;179(3):449-450. doi:10.1001/jamainternmed.2018.8137

To the Editor We read the article “Efficacy of Low-Dose Amitriptyline for Chronic Low Back Pain: A Randomized Clinical Trial” by Urquhart and colleagues,1 in which the authors found a significant reduction in disability at 3 months following treatment with amitriptyline but not at 6 months. The other outcome parameters, such as pain intensity and work absence and hindrance, were not significantly different between the amitriptyline and the control groups. Adverse effects of a drug are an important outcome measure. A drug may be effective but may not be used because of its severe adverse effects, such as reserpine for hypertension. In the study by Urquhart et al,1 use of benztropine mesylate as a comparator in the control arm has neutralized the difference in the adverse effects of amitriptyline. Amitriptyline is usually avoided in elderly individuals because of its adverse effects such as urinary retention, glaucoma, cardiac arrhythmia, confusion, etc. Was there any difference in adverse effects between patients older vs younger than 65 years? Chronic backache below the costal margin and above the gluteal fold may be owing to vitamin D deficiency or hypothyroidism, which responds to specific treatment and not to amitriptyline. Were vitamin D levels and thyroid function tests obtained? This would be more appropriate for those patients who did not respond to treatment. Figure 2B in the article needs clarification. The Ronald Morris Disability Questionnaire score ranges between 0 and 24 points.2 In the figure, the baseline disability score was more than 24. This does not match the data presented in Table 1, in which the amitriptyline group had a mean baseline disability score of 7.54 and the active comparator group had a mean score of 8.15. The analgesic effect of amitriptyline and nortriptyline compared with placebo has been reported in earlier studies.3,4 We have reported a randomized clinical trial5 comparing the efficacy of amitriptyline vs pregabalin in chronic low backache. Both the drugs were effective in reducing pain and disability at 3 months compared with baseline. In the amitriptyline group, a higher proportion of patients (57.3% vs 39.2%) had more than 50% pain relief on visual analogue scale, and more than 20% disability reduction on the Oswestry Disability Index (65.0% vs 49.5%) compared with the pregabalin group. Out of 200 patients, 93 had localized backache, 95 had radiculopathy, and 12 had lumbar canal stenosis. The pain relief was similar in all 3 groups.5 Amitriptyline appears to be a cheap and effective drug in chronic low backache, preferably prescribed for patients younger than 50 years.

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    1 Comment for this article
    Chronic Neuropathic Pain
    Paul Nelson, M.D., M.S. | Family Health Care, P.C. retired
    A remote study reported by Ian Gilron et al in a 2009 Lancet edition is probably the most remarkable pain control study. The study itself as well as its results represents a trail head endeavor. Its title says it all: "Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled cross-over trial." P values of <0.001 pervade. The dosages employed are remarkable for their minimal levels.

    See https://doi:10.1016/S0140-6736(09)61081-3 (you can locate it most easily by doing a Google Scholar search)

    Explaining this
    combination represents a unique problem that is largely over-come based on a trustworthy connection with each patient. Just remind the patient that both have been around for more than 25 years, the low dosages do not imply the presence of depression or epilepsy, and there is no habituation. The other unique issue is that the benefit usually takes 10-20 days to take effect. From a 5-7 level of recent onset pain, 3-4 will usually be the initial outcome. Low dose "Miralax" may be temporarily needed for constipation. A small increase in one month will usually achieve stable 0-2 levels of pain. Tapering off in 1-3 months will determine the value of longer usage.