Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens

TLDR

Pregabalin binds with high affinity to the alpha2‑delta subunit of voltage‑gated calcium channels, reducing excitatory neurotransmitter release. This 12‑week, double‑blind, multicentre, placebo‑controlled study evaluated the efficacy and safety of pregabalin in patients with chronic postherpetic neuralgia or painful diabetic peripheral neuropathy. Patients were randomized to placebo or to flexible‑dose (150–600 mg/day with weekly escalation) or fixed‑dose (300 mg/day for 1 week, then 600 mg/day for 11 weeks) pregabalin regimens. Pregabalin significantly lowered mean pain scores and pain‑related sleep interference versus placebo, with common adverse events of dizziness, peripheral oedema, weight gain, and somnolence, and its efficacy, tolerability, and safety are consistent with prior studies, supporting a dosing strategy that balances benefit and adverse events.

Abstract

Pregabalin binds with high affinity to the alpha2-delta subunit protein of voltage-gated calcium channels and, thereby, reduces release of excitatory neurotransmitters. This 12-week randomised, double-blind, multicentre, placebo-controlled, parallel-group study evaluated the efficacy and safety of pregabalin in patients with chronic postherpetic neuralgia (PHN) or painful diabetic peripheral neuropathy (DPN). Patients were randomised to placebo (n=65) or to one of two pregabalin regimens: a flexible schedule of 150, 300, 450, and 600 mg/day with weekly dose escalation based on patients' individual responses and tolerability (n=141) or a fixed schedule of 300 mg/day for 1 week followed by 600 mg/day for 11 weeks (n=132). Both flexible- and fixed-dose pregabalin significantly reduced endpoint mean pain score (primary outcome) versus placebo (P=0.002, P<0.001) and were significantly superior to placebo in improving pain-related sleep interference (P<0.001). The most common adverse events (AEs) for pregabalin-treated patients were dizziness, peripheral oedema, weight gain (not affecting diabetes control), and somnolence. These results are consistent with previous studies' demonstrating pregabalin's efficacy, tolerability, and safety for treatment of chronic neuropathic pain associated with DPN or PHN. Pregabalin dosing aimed at optimal balance of efficacy and tolerability provides significant pain relief and may reduce risks for AEs and therapy discontinuation.