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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.

Systematic review
Placebo-controlled comparisons
Diabetic neuropathy
Figure: Antidepressant compared with placebo in diabetic neuropathy
Postherpetic neuralgia
Atypical facial pain
Central pain
Active-controlled comparisons
Adverse effects
Related topics
Further reading

Antidepressants in neuropathic pain


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, or that antidepressants are better than anticonvulsants. What is clear is that antidepressants have an analgesic effect on top of any mood effect.

Systematic review


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

Date review completed: 1994

Number of trials included: 18 (21 placebo-controlled arms / 11 active controls)

Number of patients: 400 active versus 373 placebo controls.

Control group: placebo or active (antidepressant / analgesic / anticonvulsants / tranquillisers)

Main outcomes: Relative benefit and NNT to achieve at least 50% pain relief (with 95% confidence intervals).

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 at least 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, Figure). Desipramine and tricyclics produced the best NNTs. The overall NNT was 3.0 (2.4 to 4.0).

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

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

Postherpetic neuralgia


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

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)

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.

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 compared antidepressants with anticonvulsants directly. This showed greater benefit at lower risk with antidepressant.

Adverse effects


The number needed to harm (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.

Related topics


Anticonvulsants in chronic pain
Topical capsaicin
NNT
Relative benefit/risk

Further reading


The current review is an expansion of:


McQuay HJ, Tramer M, Nye BA, Carroll D, Wiffen PJ, Moore RA. A systematic review of antidepressants in neuropathic pain. Pain. 1996; 68: 217-227.

The following review covers a similar area, but includes headache:

France RD, Houpt JL, Ellinwood EH. Therapeutic effects of antidepressants in chronic pain. Gen Hosp Psychiatry. 1984; 6: 55-63.

Other reviews on this topic:


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

Lee R, Spencer PS. 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 JA, Denny MC. Do antidepressant medications relieve chronic low back pain? J Fam Pract. 1993 Dec; 3: 545-53.


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