Venlafaxine versus imipramine in painful polyneuropathy: a randomized, controlled trial

Neurology. 2003 Apr 22;60(8):1284-9. doi: 10.1212/


Background: Tricyclic antidepressants (TCA) are often used in the treatment of painful polyneuropathy. Venlafaxine is a serotonin and weak noradrenaline reuptake inhibitor antidepressant with a different profile of other pharmacologic actions from those of TCA.

Objective: To test if venlafaxine would relieve painful polyneuropathy and compare its possible efficacy with that of the TCA imipramine.

Methods: The study design was randomized, double blind, and placebo controlled, with a three-way crossover. Forty patients were assigned to one of the treatment sequences, and 29 completed all three study periods. The daily doses were venlafaxine 225 mg and imipramine 150 mg. During the three treatment periods, each of 4 weeks' duration, patients rated pain paroxysms, constant pain, and touch- and pressure-evoked pain by use of 0- to 10-point numeric rating scales.

Results: The sum of the individual pain scores during treatment week 4 was lower on venlafaxine (80% of baseline score; p = 0.006) and imipramine (77%; p = 0.001) than on placebo (100%) and did not show any statistical difference between venlafaxine and imipramine (p = 0.44). The individual pain scores for pain paroxysms, constant pain, and pressure-evoked pain showed a similar pattern, whereas touch-evoked pain was uncommon and was not altered by any of the drugs. Numbers needed to treat to obtain one patient with moderate or better pain relief were 5.2 for venlafaxine and 2.7 for imipramine.

Conclusion: Venlafaxine relieves pain in polyneuropathy and may be as effective as imipramine.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analgesics, Non-Narcotic / therapeutic use*
  • Cross-Over Studies
  • Cyclohexanols / therapeutic use*
  • Diabetic Neuropathies / drug therapy
  • Double-Blind Method
  • Female
  • Humans
  • Imipramine / therapeutic use*
  • Male
  • Middle Aged
  • Neuralgia / drug therapy*
  • Neurotransmitter Uptake Inhibitors / therapeutic use*
  • Norepinephrine / metabolism
  • Pain Measurement
  • Polyneuropathies / drug therapy*
  • Pressure / adverse effects
  • Serotonin / metabolism
  • Touch
  • Treatment Outcome
  • Venlafaxine Hydrochloride


  • Analgesics, Non-Narcotic
  • Cyclohexanols
  • Neurotransmitter Uptake Inhibitors
  • Serotonin
  • Venlafaxine Hydrochloride
  • Imipramine
  • Norepinephrine