Journal Article

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

Tanenberg, R. J., Malcolm, S., Irving, G., Raskin, J., Risser, R. C.

2014

Overview

Summary 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.

• Publisher: Blackwell Publishing Ltd,John Wiley & Sons, Inc
• Subject: Adult / Adverse events / Aged / Aged, 80 and over / Amines - adverse effects / Amines - therapeutic use / Analgesics - therapeutic use / Analysis of covariance / Appetite loss / Clinical medicine / Cyclohexanecarboxylic Acids - adverse effects / Cyclohexanecarboxylic Acids - therapeutic use / Diabetes / Diabetes mellitus / Diabetic neuropathy / Drug dosages / Drug therapy / Drug Therapy, Combination - methods / Drug Therapy, Combination - standards / Drug Therapy, Combination - utilization / Duloxetine / Duloxetine Hydrochloride - adverse effects / Duloxetine Hydrochloride - therapeutic use / Edema / FDA approval / Female / Gabapentin / gamma-Aminobutyric Acid - adverse effects / gamma-Aminobutyric Acid - therapeutic use / Humans / Insomnia / Laboratories / Male / Middle Aged / Nausea / Nervous system / Neuralgia / Neuralgia - drug therapy / Neurotoxicity / Orgasm / Pain / Pain Measurement / Peripheral Nervous System Diseases - complications / Peripheral Nervous System Diseases - drug therapy / Pharmacology / Pregabalin - adverse effects / Pregabalin - therapeutic use / Questionnaires / Side effects / Sleep / Sleep disorders / Toxicity / Treatment Outcome / Variance analysis / Weight