The use of gabapentin for the treatment of postherpetic neuralgia

Background: Varicella-zoster virus causes chickenpox and can reemerge later in life to cause herpes zoster or shingles. One of the most common and disabling complications of herpes zoster is postherpetic neuralgia (PHN). Objectives: This article reviews the current primary literature about the efficacy and tolerability of gabapentin for the treatment of PHN. Gabapentin pharmacokinetics and drug interactions are also reviewed. Methods: A literature search in the English language was conducted using OVID Web, which contained the following databases: MEDLINE (1966–present), EMBASE (1980–2002), Current Contents/Clinical Medicine (1999–2002), Cochrane Controlled Trials Register (1898–present), Cochrane Database of Systemic Reviews (fourth quarter, 2002), and International Pharmaceutical Abstracts (1970–2002). Search terms used were postherpetic neuralgia; zoster; gabapentin; neuropathic pain; pain; pharmacoeconomic; cost; controlled clinical trial; randomized, controlled trial; postherpetic neuralgia and gabapentin; gabapentin and pain; treatment and postherpetic neuralgia; gabapentin and age; gabapentin and gender; gabapentin and ethnicity; and gabapentin and pharmacokinetics. Results: Gabapentin displays nonlinear absorption kinetics, is minimally protein bound (<3%), has a high mean (SD) volume of distribution (50.4 [8.0] L), and is excreted via the kidneys as unchanged drug. Two randomized, placebo-controlled, parallel-group, multicenter clinical trials demonstrated the effectiveness of gabapentin at doses of up to 3600 mg/d to significantly reduce pain (P < 0.01 and P < 0.001), improve sleep (P < 0.01), and improve some parameters on the Short Form-McGill Pain Questionnaire (P < 0.05). Dizziness and somnolence were the most common side effects leading to withdrawal from the trials. The recommended dosage in adults is 300 mg at bedtime on day 1, 300 mg BID on day 2, and 300 mg TID on day 3, titrating up as needed to 2400 and 3600 mg/d. To reduce adverse events in patients with renal impairment, the dose should be adjusted based on the patient's creatinine clearance. Conclusions:Gabapentin appears to be effective and well tolerated for the short-term treatment of PHN. However, future controlled studies are needed to determine whether the effectiveness of gabapentin for PHN is maintained for >2 months, to establish the optimal dose of gabapentin for PHN, and to compare the efficacy of gabapentin with that of other pharmacologic agents used for the treatment of PHN.