Comparative safety and tolerability of duloxetine vs. pregabalin vs. duloxetine plus gabapentin in patients with diabetic peripheral neuropathic pain

Int J Clin Pract. 2014 Sep;68(9):1130-40. doi: 10.1111/ijcp.12452. Epub 2014 May 18.

Abstract

Objective: The safety and tolerability of three treatments for diabetic peripheral neuropathic pain (DPNP) were compared.

Methods: A 12-week, randomized, open-label study confirming the non-inferiority of duloxetine (N = 138) vs. pregabalin (N = 134) and the combination of duloxetine plus gabapentin (N = 135) as the primary outcome was previously published. Patients had an inadequate pain response to a stable dose of gabapentin (≥ 900 mg/day) for ≥ 5 weeks prior to study enrolment. Data from that study were assessed in this current analysis for a detailed report of safety and tolerability.

Results: Completion rates did not differ significantly between the groups. Discontinuation because of adverse events was significantly greater in the duloxetine (19.6%) vs. pregabalin group (10.4%; p = 0.04); no differences emerged between the duloxetine vs. duloxetine plus gabapentin (13.3%) groups (p = 0.19) or pregabalin vs. duloxetine plus gabapentin groups (p = 0.57). Adverse event rates varied: nausea, insomnia, hyperhidrosis and decreased appetite were reported significantly more often in patients treated with duloxetine vs. patients treated with pregabalin (each p ≤ 0.01); insomnia significantly more in patients treated with duloxetine vs. duloxetine plus gabapentin (p = 0.01); peripheral oedema significantly more in patients treated with pregabalin vs. duloxetine and duloxetine plus gabapentin (p ≤ 0.001 each) and nausea, hyperhidrosis, decreased appetite and vomiting significantly more in patients treated with duloxetine plus gabapentin vs. pregabalin (each p ≤ 0.05). At end-point, weight change differed significantly among treatment groups: patients in the pregabalin group on average gained weight (1.0 ± 0.04 kg); while, patients in the duloxetine and duloxetine plus gabapentin groups on average lost weight (-2.39 ± 0.04 and -1.06 ± 0.04 kg, respectively) (pregabalin vs. duloxetine, p ≤ 0.001; pregabalin vs. duloxetine plus gabapentin, p ≤ 0.001; duloxetine vs. duloxetine plus gabapentin, p = 0.01).

Conclusion: Duloxetine, pregabalin and duloxetine plus gabapentin were generally safe and tolerable for the treatment of DPNP.

Trial registration: ClinicalTrials.gov NCT00385671.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amines / adverse effects
  • Amines / therapeutic use*
  • Analgesics / therapeutic use
  • Cyclohexanecarboxylic Acids / adverse effects
  • Cyclohexanecarboxylic Acids / therapeutic use*
  • Drug Therapy, Combination / methods
  • Drug Therapy, Combination / standards*
  • Drug Therapy, Combination / statistics & numerical data
  • Duloxetine Hydrochloride / adverse effects
  • Duloxetine Hydrochloride / therapeutic use*
  • Female
  • Gabapentin
  • Humans
  • Male
  • Middle Aged
  • Neuralgia / drug therapy
  • Pain Measurement
  • Peripheral Nervous System Diseases / complications
  • Peripheral Nervous System Diseases / drug therapy*
  • Pregabalin / adverse effects
  • Pregabalin / therapeutic use*
  • Treatment Outcome*
  • gamma-Aminobutyric Acid / adverse effects
  • gamma-Aminobutyric Acid / therapeutic use*

Substances

  • Amines
  • Analgesics
  • Cyclohexanecarboxylic Acids
  • Pregabalin
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Duloxetine Hydrochloride

Associated data

  • ClinicalTrials.gov/NCT00385671