Which antidepressants are most useful in neuropathic pain?
Tricyclic antidepressants (e.g., amitriptyline, nortriptyline, desipramine, imipramine) are known to have analgesic benefit independent of antidepressant effect, likely through inhibition of reuptake of norepinephrine and serotonin at the spinal dorsal horn. It is thought that lower doses than what is required for treatment of depression are sufficient for pain benefit, and they continue to be first-line treatment for DPN and PHN. Concern for cardiac toxicity and anticholinergic side effects such as orthostatic hypotension, urinary retention, and dry mouth tend to be limiting, though nortriptyline may be the best tolerated. Selective norepinephrine and SNRIs such as duloxetine and venlafaxine may be even better tolerated, but may take several weeks to become effective. For SNRIs, the dose that treats neuropathic pain is similar to the antidepressant dose. Duloxetine has shown sustained efficacy in painful DPN and has some suggestive evidence in HIV-associated neuropathy and CIDP, but has not been formally studied in other neuropathies. Meanwhile, venlafaxine has also some efficacy in DPN, but not in PHN.