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Tricyclic antidepressants for neuropathic pain

Näytönastekatsaukset
Maija Haanpää and Aleksi Raudasoja
3.3.2026

Level of evidence: C

Tricyclic antidepressants may decrease neuropathic pain.

A systematic review «Soliman N, Moisset X, Ferraro MC, et al. Pharmacot...»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 p...»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.

Table 1. Description of the included studies
Reference Study type Population Intervention and comparison Outcomes Risk of bias
RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis
«Soliman N, Moisset X, Ferraro MC, et al. Pharmacot...»1 SR/MA Adult patients with neuropathic pain Tricyclic antidepressants vs placebo Decrease in average pain High
Table 2. Additional comments for included studies.
Reference Comments
«Soliman N, Moisset X, Ferraro MC, et al. Pharmacot...»1 Most trials were crossover trials with no or 1 week washout period which may increase the effect size. Dropouts were high (over 20%) in most trials.

Results

Table 3. Outcome 1. Pain (VAS or NRS) [0-10]
Reference Number of studies and number of patients (I/C) Follow-up time Mean (SD) I Mean (SD) C Mean difference (95% CI)
Level of evidence: Low
The quality of evidence was downgraded two times due to high risk of bias.
*We calculated the effect size by using the data provided by the systematic review using random effects meta-analysis.
I= intervention; C=comparison; CI=confidence interval
«Soliman N, Moisset X, Ferraro MC, et al. Pharmacot...»1 12 trials, 435 patients 3-9 weeks Not reported 4.91 -0.99 (-1.36 to -0.62)*
Relative change:
-20 % (95% CI -28 % to -13 %)

References

  1. 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 «PMID: 40252663»PubMed
  2. Leucht C, Huhn M, Leucht S. Amitriptyline versus placebo for major depressive disorder. Cochrane Database Syst Rev 2012;12(12):CD009138 «PMID: 23235671»PubMed