Pregabalin in the Treatment of Postherpetic Neuralgia Resistant to Gabapentin

Postherpetic Neuralgia

The symptoms of shingles (herpes zoster) arise from the reactivation of the endogenous varicella-zoster virus (VZV), which persists in a latent form in the sensory ganglia after having had chickenpox (varicella). This disease typically begins as several days of unilateral pain before the characteristic rash appears. A relatively common and unfortunately serious complication is the development of postherpetic neuralgia (PHN), defined as pain lasting 6 months or longer after the acute outbreak of VZV has healed. It occurs in about 10–15% of patients who have had chickenpox. The painful symptoms are often of high intensity, affecting sleep quality (in more than half of the patients) and significantly reducing quality of life.

Treatment Options 

Treatment of PHN is often suboptimal. We are gradually moving away from previously used medications in clinical practice. Tricyclic antidepressants have a higher number of side effects. The effect of nonsteroidal anti-inflammatory drugs (NSAIDs), which work relatively well for nociceptive pain, is very limited in the case of PHN.

Gabapentin has proven to be suitable in many clinical studies conducted in several countries, but an enormous drawback is its method of clinical use. Therapy must be initiated with a low dose and gradually titrated, with dosing 3 times a day possibly leading to patient non-compliance.

Pregabalin is currently recommended as the first-line treatment for PHN patients for its efficacy and favorable safety profile. Its binding leads to a reduction in calcium influx at nerve endings, thereby decreasing the release of several neurotransmitters (glutamate, norepinephrine, substance P). Clinically, it is advantageous that slow titration is not necessary, and an initial dose of 150 mg/day significantly reduces pain intensity. A dose of 300–600 mg/day has been shown to be safe and well-tolerated. Besides reducing pain, it also improves sleep quality, as evidenced by numerous clinical studies focused on patients with neuropathic pain.

Findings from Clinical Studies

In a double-blind, placebo-controlled study involving 370 patients with PHN (van Seventer et al.), pregabalin proved to be clearly effective compared to placebo. Pain scores significantly decreased within the first week of therapy. Its effect was maintained throughout the 13-week duration of the study, and sleep quality was also better in the pregabalin-treated group. Adverse events were mild to moderate in severity and occurred in a very low percentage of patients.

Derry et al. published results from a collection of 45 studies on the use of pregabalin in PHN therapy. The total number of subjects exceeded 11,000, including patients with PHN as well as those with diabetic neuropathy or mixed neuropathy. Oral doses of pregabalin ranged from 150–600 mg/day. In the case of PHN, there was a reduction in pain intensity compared to placebo.

Conclusion

The main conclusion, particularly important for clinical practice, is the recommended dosing of pregabalin. The most effective daily dose appears to be 300–600 mg, achieving at least a 50% reduction in pain intensity. This effect undoubtedly goes hand in hand with the improvement of sleep quality and a favorable impact on the overall quality of life for patients with postherpetic neuralgia.

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Sources:
1. van Seventer R., Feister H. A., Young J. P. jr. et al. Efficacy and tolerability of twice-daily pregabalin for treating pain and related sleep interference in postherpetic neuralgia: a 13-week, randomized trial. Curr Med Res Opin 2006; 22 (2): 375–384, doi: 10.1185/030079906x80404.
2. Liang L., Li X., Zhang G. et al. Pregabalin in the treatment of herpetic neuralgia: results of a multicenter Chinese study. Pain Med 2015; 16 (1): 160–167, doi: 10.1111/pme.12564.
3. Derry S., Bell R. F., Straube S. et al. Pregabalin for neuropathic pain in adults. Cochrane Database Syst Rev 2019; 1 (1): CD007076, doi: 10.1002/14651858.CD007076.pub3.