Antidepressants for neuropathic pain

Cochrane Database Syst Rev. 2005 Jul 20;(3):CD005454. doi: 10.1002/14651858.CD005454.


Background: For many years antidepressant drugs have been used to manage neuropathic pain, and are often the first choice treatment. It is not clear, however, which antidepressant is more effective, what role the newer antidepressants can play in treating neuropathic pain, and what adverse effects are experienced by patients.

Objectives: To determine the analgesic effectiveness and safety of antidepressant drugs in neuropathic pain. Migraine and headache studies were not considered.

Search strategy: Randomised trials of antidepressants in neuropathic pain were identified in MEDLINE (1966 to Dec 2003); EMBASE (1980 to Dec 2003); the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2004, Issue 1; and the Cochrane Pain, Palliative and Supportive Care Trials Register (May 2002). Additional reports were identified from the reference list of the retrieved papers, and by contacting investigators.

Selection criteria: Randomised trials reporting the analgesic effects of antidepressant drugs in adult patients, with subjective assessment of pain of neuropathic origin. Studies that included patients with chronic headache and migraine were excluded.

Data collection and analysis: Two reviewers agreed the included studies, extracted data, and assessed methodological quality independently. Fifty trials of 19 antidepressants were considered eligible (2515 patients) for inclusion. Relative Risk (RR) estimates and Number-Needed-to-Treat (NNTs) were calculated from dichotomous data for effectiveness and adverse effects.

Main results: Tricyclic antidepressants (TCAs) are effective treatments for the treatment of neuropathic pain. Amitriptyline has an NNT of 2 (95%CI 1.7 to 2.5) RR 4.1(95%CI 2.9-5.9) for the achievement of at least moderate pain relief. There is limited evidence for the effectiveness of the newer selective serotonin reuptake inhibitor antidepressant drugs (SSRIs). There were insufficient data for an assessment of evidence of effectiveness for other antidepressants such as St Johns Wort, venlafaxine and L-tryptophan. For diabetic neuropathy the NNT for effectiveness was 1.3 (95%CI 1.2 to 1.5) RR 12.4(95%CI 5.2-29.2) (five studies); for postherpetic neuralgia 2.2 (95%CI 1.7 to 3.1), RR 4.8(95%CI 2.5-9.5)(three studies). There was evidence that TCAs are not effective in HIV-related neuropathies. The number needed to harm(NNH) for major adverse effects defined as an event leading to withdrawal from a study was 16 (95%CI: 10-45). The NNH for minor adverse effects was 4.6 (95%CI 3.3-6.7)

Authors' conclusions: Antidepressants are effective for a variety of neuropathic pains. The best evidence available is for amitriptyline. There are only limited data for the effectiveness of SSRIs. It is not possible to identify the most effective antidepressant until more studies of SSRIs are conducted.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Analgesics / therapeutic use*
  • Antidepressive Agents / therapeutic use*
  • Humans
  • Nervous System Diseases / drug therapy*
  • Neuralgia / drug therapy
  • Pain / drug therapy*
  • Randomized Controlled Trials as Topic


  • Analgesics
  • Antidepressive Agents