Comparison of the effectiveness of amitriptyline and gabapentin on chronic neuropathic pain in persons with spinal cord injury

Arch Phys Med Rehabil. 2007 Dec;88(12):1547-60. doi: 10.1016/j.apmr.2007.07.038.


Objective: To test the hypotheses that both amitriptyline and gabapentin are more effective in relieving neuropathic pain than an active placebo, diphenhydramine.

Design: Randomized, controlled, double blind, triple crossover 8-week trial.

Setting: Veterans Affairs medical center.

Participants: Community dwelling adults with spinal cord injury (N=38) were recruited by telephone, letters, and flyers.

Intervention: Eight-week trial each of amitriptyline, gabapentin, and diphenhydramine.

Main outcome measures: Pain intensity measured with a 10-cm visual analog scale (VAS) and an 11-point (0-10) numeric rating scale (NRS) and depressive symptomatology measured with the Center for Epidemiologic Studies Depression Scale-Short Form (CESD-SF).

Results: Baseline VAS scores for participants with low (< 10) CESD-SF scores was 4.61 and for those with high scores (> or = 10) it was 7.41. At week 8, in participants with high baseline CESD-SF scores, amitriptyline (mean, 4.21) was more effective than diphenhydramine (mean, 6.67; P=.035), and there was a nonsignificant trend suggesting that amitriptyline may be more effective than gabapentin (mean, 6.68; P=.061). Gabapentin was no more effective than diphenhydramine (P=.97). There was no significant difference among the medications for those with lower CESD-SF scores. Results could not be attributed to dropout rates, order or dose of medications, amount of medication taken for breakthrough pain, or side effects.

Conclusions: Amitriptyline is more efficacious in relieving neuropathic pain than diphenhydramine at or below the level of spinal cord injury in people who have considerable depressive symptomatology.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Amines / adverse effects
  • Amines / therapeutic use*
  • Amitriptyline / adverse effects
  • Amitriptyline / therapeutic use*
  • Analgesics / adverse effects
  • Analgesics / therapeutic use*
  • Analysis of Variance
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Cross-Over Studies
  • Cyclohexanecarboxylic Acids / adverse effects
  • Cyclohexanecarboxylic Acids / therapeutic use*
  • Diphenhydramine / adverse effects
  • Diphenhydramine / therapeutic use*
  • Double-Blind Method
  • Female
  • Gabapentin
  • Histamine H1 Antagonists / adverse effects
  • Histamine H1 Antagonists / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Mononeuropathies / etiology
  • Pain / drug therapy*
  • Pain / etiology*
  • Pain Measurement
  • Spinal Cord Injuries / complications*
  • gamma-Aminobutyric Acid / adverse effects
  • gamma-Aminobutyric Acid / therapeutic use*


  • Amines
  • Analgesics
  • Antidepressive Agents, Tricyclic
  • Cyclohexanecarboxylic Acids
  • Histamine H1 Antagonists
  • Amitriptyline
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Diphenhydramine