Equivalency of tricyclic antidepressants in open-label neuropathic pain study

Acta Neurol Scand. 2014 Feb;129(2):132-41. doi: 10.1111/ane.12169. Epub 2013 Aug 13.


Objectives: To compare adverse effects, tolerability and efficacy of the tricyclic antidepressants (TCAs) amitriptyline and nortriptyline in management of neuropathic pain due to peripheral neuropathy (PN).

Materials & methods: We performed a prospective open-label flexible-dosing comparison of monotherapy or adjuvant therapy using amitriptyline or nortriptyline in PN-associated neuropathic pain. Primary outcomes were quantitative adverse effects and discontinuation rates. Secondary outcomes assessed changes in pain severity, quality of life, disability, sleep efficacy, mood and anxiety, and global improvement. Assessments occurred at 3 and 6 months after initiation. Our hypothesis was that nortriptyline would have better tolerance than amitriptyline.

Results: A total of 228 PN patients were enrolled approximately equally for monotherapy and adjuvant therapy. Adverse effects and discontinuation rates were similar between amitriptyline and nortriptyline interventions. Weight gain was more common with amitriptyline, while nortriptyline use was associated with greater prevalence of dry mouth. Secondary outcome measures were similar in both groups, demonstrating improvement from baseline.

Conclusions: Amitriptyline and nortriptyline are equivalent for overall adverse effects and discontinuation rates. Either TCA should be equally considered for use in neuropathic pain due to PN. When used as monotherapy or as part of adjuvant therapy, either TCA can be expected to provide approximately 23-26% visual analog scale pain reduction if tolerated. Discontinuations due to inefficacy or adverse effects can be anticipated in 26-37% of patients initiated on either TCA for PN-associated neuropathic pain.

Keywords: chronic pain C10.597.617.258; polyneuropathy C10.668.829.800; tricyclic antidepressants D27.505.954.427.700.122.055.

Publication types

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

MeSH terms

  • Amitriptyline / adverse effects
  • Amitriptyline / therapeutic use*
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuralgia / drug therapy*
  • Neuralgia / etiology
  • Nortriptyline / adverse effects
  • Nortriptyline / therapeutic use*
  • Pain Measurement
  • Peripheral Nervous System Diseases / complications
  • Peripheral Nervous System Diseases / drug therapy*
  • Therapeutic Equivalency
  • Treatment Outcome
  • Treatment Refusal


  • Antidepressive Agents, Tricyclic
  • Amitriptyline
  • Nortriptyline