Topical application of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomized, double-blind, placebo-controlled study

Br J Clin Pharmacol. 2000 Jun;49(6):574-9. doi: 10.1046/j.1365-2125.2000.00200.x.


Aims: To assess the analgesic efficacy of topical administration of 3.3% doxepin hydrochloride, 0.025% capsaicin and a combination of 3. 3% doxepin and 0.025% capsaicin in human chronic neuropathic pain.

Methods: A randomized, double-blind, placebo-controlled study of 200 consenting adult patients. Patients applied placebo, doxepin, capsaicin or doxepin/capsaicin cream daily for 4 weeks. Patients recorded on a daily basis overall pain, shooting, burning, paraesthesia and numbness using a 0-10 visual analogue scale during the week prior to cream application (baseline levels) and for the 4 week study period. Side-effects and desire to continue treatment were also recorded.

Results: Overall pain was significantly reduced by doxepin, capsaicin and doxepin/capsaicin to a similar extent. The analgesia with doxepin/capsaicin was of more rapid onset. Capsaicin significantly reduced sensitivity and shooting pain. Burning pain was increased by doxepin and by capsaicin and to a lesser extent by doxepin/capsaicin. Side-effects were minor. One patient requested to continue placebo cream, 17 doxepin cream, 13 capsaicin and 9 the combination of doxepin and capsaicin.

Conclusions: Topical application of 3.3% doxepin, 0.025% capsaicin and 3.3% doxepin/0. 025% capsaicin produces analgesia of similar magnitude. The combination produces more rapid analgesia.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Topical
  • Adult
  • Antidepressive Agents, Tricyclic / administration & dosage*
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Capsaicin / administration & dosage*
  • Capsaicin / adverse effects
  • Capsaicin / therapeutic use*
  • Chronic Disease
  • Double-Blind Method
  • Doxepin / administration & dosage*
  • Doxepin / adverse effects
  • Doxepin / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pain / drug therapy*
  • Pain / etiology
  • Pain / psychology
  • Pain Measurement
  • Paresthesia / drug therapy
  • Peripheral Nervous System Diseases / complications*


  • Antidepressive Agents, Tricyclic
  • Doxepin
  • Capsaicin