Tricyclic antidepressants for neuropathic pain

A systematic review «Soliman N, Moisset X, Ferraro MC, et al. Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: a systematic review and meta-analysis. Lancet Neurol 2025;24(5):413-428 »1 measured the effectiveness of tricyclic antidepressants on neuropathic pain, including 12 randomized trials. A reanalysis of these trials suggested a mean 1-point decrease (95% CI -1.36 to -0.62) in average pain at 3-9 weeks follow up, translating to about 20 % decrease in pain (95% CI -28 % to -13 %).

We were unable to find data on specific harms. The same systematic review found RD of 5.8 % (3.0 % to 8.8 %) for withdrawals due to side effects.

Indirect evidence on amitriptyline for depression suggest increased risk of constipation (22 % vs 7,8 %, risk difference 14 %), dry mouth (71 % vs 19 %, RD 52 %), vision problems (18 % vs 5,6 %, RD 12 %), tachycardia (17 % vs 3,6 %, RD 13 %), dizziness (22 % vs 9,4 %, RD 13 %), somnolence (43 % vs 12,8 %, RD 30 %), tremor (16 % vs 3,2 %, RD 13 %), dyspepsia (12 % vs 1,8 %, RD 10 %), increased appetite (17 % vs 5,2 %, RD 12 %), weight gain (20 % vs 2%, RD 18 %), and sexual dysfunction (16 % vs 1 %, RD 15 %) «Leucht C, Huhn M, Leucht S. Amitriptyline versus placebo for major depressive disorder. Cochrane Database Syst Rev 2012;12(12):CD009138 »2.

However, the doses are higher than used in treatment of neuropathic pain, and therefore, the risk of harms are likely smaller in treatment of neuropathic pain.

The quality of evidence was downgraded two times due to high risk of bias.

Results