Amitriptyline vs. Pregabalin in Painful Diabetic Neuropathy: A Randomized Double Blind Clinical Trial

Diabet Med. 2009 Oct;26(10):1019-26. doi: 10.1111/j.1464-5491.2009.02806.x.


Aims: To compare the efficacy and safety of pregabalin and amitriptyline in alleviating pain associated with diabetic peripheral neuropathy.

Methods: A randomized, double-blind, crossover, active-control, clinical trial with variable dose titration was carried out (n = 51). Amitriptyline orally, at doses of 10, 25 and 50 mg at night-time and pregabalin orally, at doses of 75, 150 and 300 mg twice daily, by optional titration was used. Each drug treatment was of 5 weeks. There was a placebo washout period for 3 weeks between the two drugs. Assessment for pain relief, overall improvement and adverse events were carried out.

Results: Good, moderate and mild pain relief were noted in 21 (48%), 6 (13%) and 7 (15%) patients on pregabalin and 15 (34%), 5 (11%) and 12 (27%) patients on amitriptyline, respectively, by patient's global assessment of efficacy and safety. Patient and physician's global assessment, McGill pain questionnaire, Likert pain scale and Patient Global Impression of Change showed no significant difference between the treatments, although improvement with both treatments was seen from the first week. Of the 52 adverse events reported, 34 (65.4%) were with amitriptyline, drowsiness being the commonest [in 19 (43%) patients]. Pregabalin caused adverse events in 18 (25%), of which drowsiness was the most common in nine (20%) patients. The preferred pregabalin dose was 150 mg twice daily.

Conclusions: As there are few differences between the two treatments in efficacy, pregabalin 150 mg twice daily might be the alternative choice as it is associated with fewer adverse effects in our population.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Amitriptyline / administration & dosage*
  • Analgesics, Non-Narcotic / administration & dosage*
  • Diabetic Neuropathies / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pain / drug therapy*
  • Pregabalin
  • Treatment Outcome
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / analogs & derivatives*


  • Analgesics, Non-Narcotic
  • Amitriptyline
  • Pregabalin
  • gamma-Aminobutyric Acid