Introduction

Gabapentin is well supported for treating neuropathic pain, particularly postherpetic neuralgia (PHN), by modulating calcium-channel function and reducing neurotransmitter release. PHN prevalence and severity increase with age and are often resistant to standard analgesics. Gabapentin’s short half-life, nonlinear absorption, and dose-limiting side effects reduce convenience. An extended‑release gastric‑retentive formulation (G‑GR) improves absorption and enables once‑daily dosing with comparable exposure, showing significant pain reduction in some clinical trials.

Aim

To assess the safety and efficacy of once-daily gastroretentive formulation of gabapentin (G-GR) 1800 mg in patients with postherpetic neuralgia.

Method

Study Design

Patient Profile 

Treatment Strategy 

• Patients completed a 2‑week dose‑titration period (in which the starting doses were 300 mg/d, increased to a ceiling daily dose of 1800 mg/d), followed by 8 weeks of stable dosing and a 1‑week dose‑tapering phase
• The patients recorded their pain intensity score and the degree to which pain interfered with sleep daily in an electronic diary over the 11 weeks

Endpoints

• Change in the baseline observation carried forward (BOCF) in average daily pain score
• Sleep interference
• Adverse events (AEs)
• Investigator-rated clinician global impression of change (CGIC)
• Patient-reported patient global impression of change (PGIC) 

Results

• Of the 452 enrolled patients, 377 (84% G-GR and 83% placebo) completed the study
• Baseline characteristics of cohort are as follows-
  1. Mean age 65.6 years
  2. Baseline average daily pain score was 6.6 and 6.5 for the G-GR and placebo groups respectively
  3. Mean duration of pain was 19.3 and 21.1 months in the G-GR and placebo groups respectively
• There was a significant reduction in the BOCF change in average daily pain intensity in G-GR group as compared with placebo (−2.1 vs. −1.6; p=0.013)
• Higher proportion of patients in the G-GR group reported at least a 50% reduction in the average daily pain score from baseline to BOCF endpoint; 29.5% vs 22.6%
• More G-GR-treated patients reported “much” or “very much” improvement on the PGIC; 42.7% vs 33.5% and on the CGIC; 44.1% vs 33.9% as compared to placebo
• Sleep interference was reduced with G-GR (−2.3 vs. −1.59; p<0.0001), although this was considered statistically not significant based on a stringent hierarchical statistical paradigm
• The incidence of AEs was 53.4% in the G-GR group vs 39.8% in the placebo group, the most common AEs were dizziness (G-GR, 11.3% vs. placebo, 1.7 %) and somnolence (G-GR, 5.4% vs. placebo, 3.0%)

Conclusion

Clin J Pain. 2013 Apr;29(4):281-288. Doi: 10.1097/AJP.0b013e318258993e.