Pregabalin shows efficacy in treatment for postherpetic neuralgia

January 2006

An episode of acute herpes zoster is frequently complicated by postherpetic neuralgia.

Postherpetic neuralgia is frequently associated with burning, unbearable itching and an electric shocklike pain in the area of the rash.

Other frequent manifestations of postherpetic neuralgia are sleep and mood disturbances, social withdrawal and poor quality of life. Observational studies have shown that individuals may be symptomatic for more than 12 months after resolution of the initial rash. The literature does not offer a clear definition for postherpetic neuralgia. The time interval used in the definitions ranges from one to six months following resolution of the herpetic rash. This variance in definitions makes comparisons of clinical trials difficult, especially when trying to determine the superiority of one treatment modality over another. Common treatments for postherpetic neuralgia include the tricyclic antidepressants, amitriptyline and imipramine and gabapentin.

The FDA approved pregabalin for the management of postherpetic neuralgia. Other approved indications include adjunctive therapy of partial onset seizures and management of neuropathic pain associated with diabetic neuropathy.

Pregabalin is a GABA analogue that is closely related to gabapentin. Pregabalin does not bind to GABA receptors nor does it affect uptake or degradation of GABA. Pregabalin binds to alpha₂-delta subunits in central nervous system tissues. This reduces calcium influx at the nerve terminal, which in turn reduces the release of several neurotransmitters. The result of these actions is pregabalin’s analgesic, anxiolytic and anticonvulsant activity. Pregabalin is much more potent than gabapentin and achieves its efficacy in lower doses. The therapeutic index of pregabalin is increased when compared with gabapentin.

Pregabalin is available in capsules with more than 90% oral bioavailability and a five-hour half-life. Pregabalin has negligible hepatic metabolism and is not likely to have significant drug-drug interactions. The kidneys, however, primarily excrete pregabalin, and doses should be adjusted for impaired renal function.

Pregabalin vs. placebo

There are two published clinical trials of pregabalin vs. placebo for the treatment of postherpetic neuralgia. These trials demonstrate similar efficacy and safety of pregabalin, but they used different methods and definitions of postherpetic neuralgia.

Dworkin and colleagues studied 600 mg/day of pregabalin vs. placebo for the treatment of postherpetic neuralgia in an eight-week, double-blind, multicentered trial conducted in the United States.

Individuals qualified for the study if pain continued for at least three months following resolution of the herpes zoster rash. (Mean duration of pain was 30 months.) The pregabalin group had a significant improvement in pain scores by the second full day of treatment when compared with placebo. By the end of the first week, there were also significant improvements in sleep disturbance scores and quality-of-life measures. Most individuals in both arms reported adverse effects to the treatment: 87% of the pregabalin group and 67% of the placebo group. The most common adverse effects were dizziness and somnolence; 11% of the study withdrawals in the pregabalin group were due to somnolence. Zero percent of the withdrawals in the pregabalin group were due to a lack of efficacy compared with 7% of the withdrawals in the placebo group.

Sabatowski and colleagues studied two fixed doses — 150 mg/day and 300 mg/day — of pregabalin vs. placebo in a multinational trial conducted in Europe and Australia. Individuals qualified for the trial if they continued to have pain for more than six months following resolution of the herpetic rash. (Mean duration of pain was 40 months.) Both pregabalin groups showed significant improvement in pain scores and significant reductions in sleep disturbance scores during the first week of therapy compared with placebo. Researchers also saw improvements in quality-of-life scores.

There are several limitations to these studies that are worth mentioning. First, both studies were for eight weeks. Therefore, the long-term effects and/or benefits of pregabalin remain unknown.

Second, both studies allowed the participants to continue taking stable regimens of analgesics and/or antidepressants throughout the study period. The proportion of patients continuing the concomitant medications, however, was similar across all study groups. Use of these medications did not appear to influence the study results.

Third, most individuals enrolled in the study had symptomatic postherpetic neuralgia for more than two years, indicating that the study patients were most likely resistant to other conventional therapies.

Excellent efficacy

Pregabalin has been studied in more than 10,000 people and has an acceptable safety profile. Dizziness and somnolence are the most commonly reported adverse effects, followed by peripheral edema, dry mouth and weight gain. These adverse effects appear to be dose related. Some individuals reported euphoria while taking pregabalin. This drug is designated as a schedule V controlled substance.

The recommended initial dose of pregabalin for postherpetic neuralgia is either 75 mg twice daily or 50 mg three times daily. Dose may be increased to 300 mg/day (150 mg twice daily or 100 mg three times daily), depending on patient response and tolerability.

Pregabalin shows excellent efficacy in the treatment of postherpetic neuralgia, and the drug will play a vital role in treating this debilitating condition. There are no data, however, comparing pregabalin to other agents that are also effective in treating postherpetic neuralgia.

The American Academy of Neurology has recommended pregabalin as one of the first-line agents to choose from in its guidelines on the treatment of postherpetic neuralgia.

For more information:

• Dubinsky RM, Kabbani H, El-Chami Z, et al. Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2004;63:959-965.
• Sabatowski R, Galvez R, Cherry DA, et al. Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomized, placebo-controlled clinical trial. Pain. 2004;109:26-35.
• Dworkin RH, Corbin AE, Young JP, et al. Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology. 2003;60:1274-1283.