Postherpetic neuralgia is characterized by excruciating pain that affects up to 15 percent of patients who have had herpes zoster (shingles). Postherpetic neuralgia is most prevalent in persons over 60 years of age. Treatment with analgesics is generally ineffective, although symptom relief has been documented with tricyclic antidepressants alone, or with tricyclic antidepressants in combination with carbamazepine or opioids. Tricyclic antidepressants are most effective, but severe adverse effects and contraindication in many patients with cardiovascular disease may limit their use. Gabapentin may be promising in these patients, as it reportedly relieves intractable neuropathic pain and reflex sympathetic dystrophy. Rowbotham and colleagues of the Gabapentin Postherpetic Neuralgia Study Group evaluated the effectiveness of gabapentin in reducing the pain associated with postherpetic neuralgia.
Adult patients who had postherpetic neuralgia for at least three months after healing of a herpes zoster rash were eligible for this randomized controlled trial if they rated their pain at a score of at least 40 on a 100-point scale. Any medications that could interfere with their pain or their assessment of pain were discontinued at baseline, although stable dosages of narcotics or tricyclic antidepressants could be continued. Patients with serious or unstable medical conditions were excluded from the study. All patients kept a pain diary and, at each of four follow-up visits, patients completed a pain questionnaire. Patients who met the study criteria were randomized to receive either a placebo or gabapentin, beginning at 300 mg daily. The dosage was gradually increased over four weeks to a maximum of 3,600 mg daily in three divided doses. Patients who could not tolerate the maximum dosage were maintained on the highest tolerable dosage, with a minimum of 1,200 mg daily required for continuation in the study. The primary end point of the study was a change in average daily pain rating from baseline, although sleep parameters, mood and quality of life were also assessed.
Of the 229 patients enrolled in the study, 45 (15 percent) dropped out because of adverse effects associated with medication or placebo. Attrition was comparable between groups. By the end of the study, 33 percent of the treatment group reported significant improvement in average daily pain scores, compared with only 7.7 percent improvement in the placebo group. This reduction took place by the end of week 2. Sleep ratings, mood and overall quality of life also improved in the treatment group. Nearly one half of the patients receiving gabapentin reported moderate or much improvement overall, compared with only 12 percent of patients taking placebo. In fact, almost 60 percent of patients taking placebo reported no change in pain. Adverse effects reported by the treatment group included somnolence, dizziness, peripheral edema and ataxia.
The authors conclude that gabapentin appears to be a safe, effective first-line therapy for postherpetic neuralgia, although studies that directly compare its effectiveness with that of tricyclic antidepressants are needed.