Antidepressants in the treatment of neuropathic pain

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Basic Clin Pharmacol Toxicol. 2005 Jun;96(6):399-409.

Antidepressants in the treatment of neuropathic pain.

Sindrup SH, Otto M, Finnerup NB, Jensen TS.

Department of Neurology, Odense University Hospital, Odense, Denmark.

Neuropathic pain is due to lesion or dysfunction of the peripheral or

central nervous system. Tricyclic antidepressants and anticonvulsants

have long been the mainstay of treatment of this type of pain.

Tricyclic antidepressants may relieve neuropathic pain by their

unique ability to inhibit presynaptic reuptake of the biogenic amines

serotonin and noradrenaline, but other mechanisms such as N-methyl-D-

aspartate receptor and ion channel blockade probably also play a role

in their pain-relieving effect. The effect of tricyclic

antidepressants in neuropathic pain in man has been demonstrated in

numerous randomised, controlled trials, and a few trials have shown

that serotonin noradrenaline and selective serotonin reuptake

inhibitor antidepressants also relieve neuropathic pain although with

lower efficacy. Tricyclic antidepressants will relieve one in every 2-

3 patients with peripheral neuropathic pain, serotonin noradrenaline

reuptake inhibitors one in every 4-5 and selective serotonin reuptake

inhibitors one in every 7 patients. Thus, based on efficacy measures

such as numbers needed to treat, tricyclic antidepressants tend to

work better than the anticonvulsant gabapentin and treatment options

such as tramadol and oxycodone, whereas the serotonin noradrenaline

reuptake inhibitor venlafaxine appears to be equally effective with

these drugs and selective serotonin reuptake inhibitors apparently

have lower efficacy. Head-to-head comparisons between antidepressants

and the other analgesics are lacking. Contraindications towards the

use of tricyclic antidepressants and low tolerability in general of

this drug class - may among the antidepressants - favour the use of

the serotonin noradrenaline reuptake inhibitors. A recent study on

bupropion, which is a noradrenaline and dopamine uptake inhibitor,

indicated a surprisingly high efficacy of this drug in peripheral

neuropathic pain. In conclusion, antidepressants represent useful

tools in neuropathic pain treatment and must still be considered as

first line treatments of neuropathic pain. However, without head-to-

head comparisons between antidepressants and other analgesics, it is

not possible to provide real evidence-based treatment algorithms for

neuropathic pain.