Post-Herpetic Neuralgia: New Treatment Option for a Painful Condition
Post-Herpetic Neuralgia: New Treatment Option for a Painful Condition
By Barbara Biedrzycki, RN, MSN, AOCN, CRNP
Summary—When considering treatment options for painful conditions, clinicians often rely on standard pharmacological agents that work peripherally or centrally. Acetaminophen, aspirin, nonsteroidal anti-inflammatory drugs, and even opioid analgesics often fail to provide effective pain relief for patients suffering from chronic post-herpetic neuralgia (PHN). A recent study showed gabapentin, an anticonvulsant medication, may effectively and safely alleviate the pain and sleep disturbances associated with PHN.1 Of 229 study subjects, 33.3% who received gabapentin had significant relief from pain, compared with 7.7% of placebo subjects.
More than a million new cases of herpes zoster occur annually in the United States, and 10-15% of these will develop PHN. Sixty-six percent of all cases occur in those over 50 years of age; only 10% occur in those under age 20. The percentage of people with herpes zoster who develop PHN dramatically increases to nearly half as the age of onset reaches 60.1 Herpes zoster results from the reactivation of the varicella-zoster virus (chickenpox), also known as human herpes virus 3, which resides dormantly in the dorsal root or cranial nerve ganglia. Dermatomal distribution of characteristic lesions usually occurs in the following areas: 50% thoracic, 20% cervical, 15% trigeminal, 10% lumbosacral, and 5% other.2
Post-herpetic neuralgia is defined as prolonged pain following the resolution of cutaneous lesions, identified as grouped vesicles on an erythematous base usually following the path of a dermatone.3 This pain may be severe and debilitating.
Research Rationale
If the patient receives aggressive therapy for herpes zoster, the pain may resolve within six months. However, the pain may become chronic and difficult to manage.2 Opioids, carbamazepine, and tricyclic antidepressants (TCAs) have been used to manage PHN. Current meta-analyses of 11 randomized clinical trials suggest that only TCAs give consistent pain relief. Half of patients experienced pain relief with TCAs without intolerable side effects.4 Adverse effects of TCAs may include:
• arrhythmias;
• postural hypotension;
• dry mouth;
• constipation;
• confusion;
• and urinary retention.
Those side effects often make TCAs unsuitable therapy, especially for herpes zoster patients over age 60, of whom 50% may suffer from PHN.1 It was evident that a more effective intervention with fewer side effects was desperately needed.
Gabapentin may be that intervention. Gabapentin was approved in 1994 as an anticonvulsant medication indicated as adjunctive therapy for partial seizures in epileptic individuals over age 12. Gabapentin’s mechanism of action is unknown.
Although structurally similar to gamma-aminobutyric acid (GABA), a neurotransmitter involved with the transmission and modulation of pain, gabapentin does not inhibit GABA uptake or degeneration, metabolically convert to GABA or a GABA agonist, or interact with GABA receptors.5,6
The analgesic effects of gabapentin were first noted in preclinical rat studies and later documented anecdotally when used by humans.6 Researchers set out to demonstrate the safety and effectiveness of gabapentin for PHN.
Study Methodology
A thorough double-blind, randomized, placebo-controlled, parallel-design study was conducted in 16 clinical centers throughout the United States. During an eight-week trial, 229 patients were randomized to receive gabapentin (113) or placebo (116). During a four-week titration period, gabapentin or placebo was titrated to a maximum dose of 3600 mg/day, then the dose was maintained for an additional four weeks. Stabilized use of TCAs and/or opioid analgesics prior to the study was allowed with no dose adjustments during the study.
Outcomes measures were defined as the difference in scores from baseline to final week of treatment. They included:
• a change in average daily pain score (Likert scale 0-10 with 0 being no pain and 10 the worst pain possible);
• average daily sleep scores;
• pain questionnaire;
• quality-of-life questionnaire;
• mood state profile;
• and frequency and severity of adverse reactions.
Study Results
Of the 229 study subjects, 184 (80.3%) completed the study, and 35 (15.3%) withdrew because of adverse effects. Of those, 26 withdrew because of adverse effects related to the study medication: 15 (13.3%) of the 113 gabapentin subjects and 11 (9.5%) of the 116 placebo subjects. There was no statistically significant difference in the two randomized groups considering demographic variables, time since last herpes zoster eruption, baseline average daily pain score, prior PHN medications, or concomitant medications.
At the end of the study, the daily pain score was significantly reduced in 33.3% of the gabapentin subjects, compared with 7.7% in the placebo group. The study showed that pain reduction started as early as two weeks into the study, with an additional reduction by week four. The four-week pain level was maintained and continued stable through week eight.
Gabapentin subjects reported improvement in daily sleep scores, as well as improvement in sensory and affective pain. Sixteen percent of gabapentin patients reported "no pain" at the final week, compared with 8.8% of placebo patients.
Sixty-two subjects (54.9%) receiving the gabapentin reported minor adverse side effects, as did 32 subjects (27.6%) receiving placebos. One death occurred in the placebo group, but it was considered unrelated to participation in the study. (See table showing the most frequent adverse effects, p. 27.)
Table | ||
Most Frequently Occurring Adverse Effects | ||
Adverse Effect |
|
|
Somnolence |
|
|
Dizziness |
|
|
Ataxia |
|
|
Peripheral edema |
|
|
Infection |
|
|
Pain |
|
|
Source: Rowbotham M, Harden N, Stacey B, Gabapen tin for the treatment of post-herpetic neuralgia. JAMA 1998;280:1837-42. __________________________________________________ |
Implications for Practice
Based on the safety and effectiveness evidence presented in this study, the researchers conclude that gabapentin be considered for first-line therapy for the management of pain associated with PHN. While neither this study nor any others have directly compared TCAs with gabapentin, researchers have determined, using mathematical calculations, that gabapentin may be considered at least as effective as TCAs, with fewer contraindications.1
Although higher doses were used in this study, the Physicians’ Desk Reference (Medical Economics Company, Montvale, NJ) indicates an effective dose of gabapentin is 900-1800 mg/day in three divided doses, with a maximum of 12 hours between doses; 300 or 400 mg capsule doses can be titrated over several days.
Gabapentin does not require routine monitoring of clinical lab parameters, which may be advised with other anticonvulsant medications. There is no significant pharamco kinetic interaction between gabapentin and the most commonly used anticonvulsants, including phenytoin, carbamazine, valproic acid, and phenobarbital. There is a 20% decreased bioavailability when gabapentin is given with antacids. This can be minimized by ensuring a two-hour lapse between antacids and gabapentin.
Cimetidine increases excretion of gabapentin, and the bioavailability of oral contraceptives is increased with gabapentin’s use, although neither interaction is considered clinically significant.
Patients should be warned that gabapentin will cause false-positive readings with Ames N Multistix SG dipstick for urine protein.5
Individuals with HIV infection are 20 times more likely to develop herpes zoster. Since young adults may present with herpes zoster before signs, symptoms, and clinical findings of HIV are evident, clinicians may want to evaluate younger patients for HIV risk factors and consider HIV testing.7
References
1. Rowbotham M, Harden N, Stacey B. Gabapentin for the treatment of post-herpetic neuralgia. JAMA 1998;280:1837-42.
2. Whitmore E. Common Problems of the Skin. In: Barker L, Burtn J, Zieve P, eds. Principles of Ambu latory Medicine. Baltimore: Williams & Wilkins; 1995:1470-71.
3. Sande M, Volberding P. The Medical Management of AIDS. Philadelphia: WB Saunders Co.; 1997:394.
4. Kingery WS. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. Pain 1997;123-39.
5. Medical Economics Co. Physicians’ Desk Reference. Montvale, NJ;1998:2110-13.
6. Backonja M, Beydoun A, Edwards KR, et al. Gaba pentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus. JAMA 1998;280:1831-36.
7. Carlini ME, Shandera WX. Infectious Diseases: Viral and Rickettsial. In: Tierney LM, McPhee SJ, Papadakis MA. 1999 Current Medical Diagnosis and Treatment. Stamford, CT: Appleton & Lange; 1999:1259-62.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.