Skip navigation
Acute Pain | Chronic Pain | General

Antidepressants in neuropathic pain

Clinical bottom line:

Antidepressants are effective in reducing neuropathic pain. The overall NNT for at least 50% pain relief for antidepressant compared with placebo in diabetic neuropathy was 3.0 (2.4 to 4.0) and was similar across pain conditions. 30% of patients will obtain more than 50% pain relief, 30% will have minor adverse reactions and 4% will have to stop treatment because of major adverse effects. SSRIs may be less effective, but are associated with a 50% reduction in major adverse reactions.

Antidepressants have been used for over 30 years to manage neuropathic pain, but in the UK no antidepressant has a product licence for this indication. Although many studies have been carried out, it remains difficult to determine, for example, which antidepressant is most effective, whether benefit is due to analgesic effect or mood improvement and whether antidepressants are better than anticonvulsants.

Systematic review

HJ McQuay, RA Moore. An evidence-based resource for pain relief. Oxford University Press March 1998 ISBN 0-19-262718-X.

Inclusion criteria were randomised controlled trials of antidepressants in neuropathic pain (including diabetic neuropathy, postherpetic neuralgia, atypical facial pain and central pain); placebo or antidepressant or 'other intervention' control group; full journal publication; group size at least 10; pain outcome.

A clinically relevant outcome was defined as a measure equivalent to more than 50% pain relief, and outcomes of the longest duration were selected.


Placebo-controlled comparisons.

Diabetic neuropathy

Six of 13 comparisons in diabetic neuropathy showed significant improvement over placebo (covering nine different antidepressants). Desipramine and tricyclics produced the best NNTs. The overall NNT was 3.0 (2.4 to 4.0).

Figure 1: At least 50% pain relief with antidepressant compared with placebo in diabetic neuropathy

Postherpetic neuralgia

Two of three comparisons in post-herpetic neuralgia showed significant benefit The combined NNT was 2.3 (1.7 to 3.3).

Figure 2: At least 50% pain relief with antidepressant compared with placebo in postherpetic neuralgia

Atypical facial pain

Two of two comparisons in atypical facial pain showed significant benefit. The combined NNT was 2.8 (2.0 to 4.7)

Figure 3: At least 50% pain relief with antidepressant compared with placebo in atypical facial pain

Central pain

Only one of three trials had extractable data, with an NNT of 1.7 (1.1 to 3.0) in a small number of patients.

Figure 4: At least 50% pain relief with antidepressant compared with placebo in central pain

Table: NNT and relative benefit for antidepressants compared with placebo for neuropathic pain conditions

Condition Number of trials Antidepressant improved/total Placebo improved/total Relative benefit (95%CI) NNT (95%CI)
Diabetic neuropathy 13 180/260 73/205 1.9 (1.6 to 2.4) 3.0 (2.4 to 4.0)
Postherpetic neuralgia 3 43/77 8/68 4.8 (2.4 to 9.4) 2.3 (1.7 to 3.3)
Atypical facial pain 2 62/88 30/85 2.0 (1.5 to 2.8) 2.8 (2.0 to 4.7)
Central pain 1 10/15 1/15 10 (1.5 to 69) 1.7 (1.1 to 3.0)

Active-controlled comparisons.

In three of three reports tricyclics were significantly more effective than benzodiazepines. Two of two reports showed no differences between various tricyclics.

Many of the trials demonstrated analgesic benefit without significant changes in mood measures. There was no difference in efficacy across different pain conditions. Although only one trial directly compared antidepressants with anticonvulsants, this showed greater benefit at lower risk with antidepressant.

Adverse effects

The NNH for minor adverse effects was 3.7 (2.9 to 5.2) based on 11 reports, combining across pain syndromes. For major effects the NNH was 22 (14 to 58), based on 19 reports. Effects were lower for SSRIs (fluoxetine and paroxetine) than with tricyclics.

Further reading

The current review is an expansion of:

McQuay, H. J.; Tramer, M.; Nye, B. A.; Carroll, D.; Wiffen, P. J.; Moore, R. A. A systematic review of antidepressants in neuropathic pain. Pain. 1996; 68(2-3): 217-227. ISSN: 0304-3959.

This review covers a similar area, but includes headache:

France, R. D.; Houpt, J. L.; Ellinwood, E. H. Therapeutic effects of antidepressants in chronic pain. Gen Hosp Psychiatry. 1984; 6(1): 55-63. ISSN: 0163-8343.

Other reviews covered by the current review:

Goodkin, K.; Vrancken, M. A. E.; Feaster, D. On the putative efficacy of the antidepressants in chronic, benign pain syndromes. An update. Pain Forum. 1995; 4(4): 237-247.

Lee, R.; Spencer, PSJ. Antidepressants and pain : a review of the pharmacological data supporting the use of certain tricyclics in chronic pain. Journal of International Medical Research. 1977; 5: 147-156.

Max, M. B. Thirteen consecutive well-designed randomized trials show that antidepressants reduce pain in diabetic neuropathy and postherpetic neuralgia. Pain Forum. 1995; 4(4): 248-253.

Onghena, P.; Van Houdenhove, B. Antidepressant-induced analgesia in chronic non-malignant pain: a meta-analysis of 39 placebo-controlled studies. Pain. 1992; 49: 205-19.

Turner, J. A.; Denny, M. C. Do antidepressant medications relieve chronic low back pain? J Fam Pract. 1993 Dec; 37(6): 545-53.

Related topics