Use of gabapentin for postherpetic neuralgia: Results of two randomized, placebo-controlled studies

doi:10.1016/S0149-2918(03)80320-X

Clinical Therapeutics

Volume 25, Issue 10, October 2003, Pages 2597-2608

https://doi.org/10.1016/S0149-2918(03)80320-X Get rights and content

Abstract

Background: Postherpetic neuralgia (PHN), which affects up to 70% of elderly persons with herpes zoster, can have debilitating effects, including physical and social disability and significant psychological distress. A variety of agents have been used, either singly or in combination, to control PHN, including topical and oral analgesics, antidepressants, and antiepileptic drugs (AEDs). However, PHN often proves refractory to these therapies.

Objectives: This article reviews available data on the use of the newer AED gabapentin for the control of PHN.

Methods: A MEDLINE search was undertaken to identify all randomized, placebo-controlled trials on the use of gabapentin in PHN. The search terms were gabapentin and postherpetic neuralgia.

Results: The literature search identified 2 published studies of the efficacy of gabapentin in a total of 563 patients with PHN that had persisted for at least 3 months after the healing of herpes zoster rash. The studies employed multipple outcome measures, including visual analog and Likert scales for pain intensity, and quality-of-life and functional measures that included the Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and the Profile of Mood States. At maximum target dosages of 1800 to 3600 mg/d, gabapentin prodcued significant reductions in mean daily pain scores compared with placebo on both visual analog (P < 0.001) and Likert scales (P < 0.01). Improvements were also seen on the

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Comparison of Two Different Pulsed Radiofrequency Modes for Prevention of Postherpetic Neuralgia in Elderly Patients With Acute/Subacute Trigeminal Herpes Zoster
2022, Neuromodulation
Citation Excerpt :
The SF-3621,22 was used to assess the health of patients. The questionnaire, which can be completed in just 6–9 min, assesses nearly all conceptual domains of the substantially longer generic self-administered questionnaires that have been used in other studies.23 The scores for each domain—bodily pain, general health, mental health, physical function, physical role, role-emotional, social function, and vitality—were recorded before treatment and on day 7 and months 1, 3, and 6 after treatment.
Trigeminal postherpetic neuralgia (PHN) is often refractory to treatment. Pulsed radiofrequency (PRF) neuromodulation can help in preventing PHN after herpes zoster. This study aimed to compare the efficacy and safety of two different PRF modes on gasserian ganglion neuromodulation in elderly patients with acute/subacute trigeminal herpes zoster.
A total of 120 elderly patients with acute or subacute (within past three months) trigeminal herpes zoster were randomized to receive either a single cycle of high-voltage, long-duration PRF (HL-PRF group; N = 60) or three cycles of standard PRF (S-PRF group; N = 60). Patients were followed up for six months after treatment. Visual analog scale (VAS) pain score, 36-Item Short Form Health Survey (SF-36) score, and pregabalin at baseline and at different time points during follow-up were recorded.
VAS and SF-36 scores declined significantly from baseline levels in both groups (p < 0.001). The scores were significantly lower in the HL-PRF group than in the S-PRF group at some time points (p < 0.05). The mean dose of pregabalin was significantly lower in the HL-PRF group than in the S-PRF group on days 3, 14, and 28 after treatment (p < 0.05). No serious adverse events occurred in either group.
HL-PRF neuromodulation of the gasserian ganglion appears to be more effective than S-PRF for preventing PHN in the elderly.
ChiCTR2000038775.
Gabapentin for the treatment of hot flashes in women with natural or tamoxifen-induced menopause: A systematic review and meta-analysis
2009, Clinical Therapeutics
Background: Various nonhormonal agents have been used for the treatment of hot flashes in women with natural or tamoxifen-induced menopause. Some studies have reported that gabapentin appears to be an effective and well-tolerated treatment modality.
Objective: To investigate the efficacy and tolerability of gabapentin for the treatment of menopausal hot flashes, we performed a systematic review of all trials reporting on the efficacy and tolerability of gabapentin in women with hot flashes and a meta-analysis of the randomized controlled trials (RCTs) conducted in this patient population.
Methods: For the systematic review, a literature search was conducted through MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for articles published in English from inception of the databases through November 2008. The reference sections of retrieved articles were searched, and a manual search of key journals and abstracts from major meetings in clinical pharmacology was conducted. To be included in the meta-analysis, RCTs had to compare gabapentin with placebo in the treatment of hot flashes in women with natural or tamoxifen-induced menopause, regardless of the sample size, dosage used, duration of treatment, or frequency of the episodes. Uncontrolled and openlabel trials were reviewed but excluded from the meta-analysis. The percent reduction in hot flash frequency (relative to baseline) and the composite score (summation of the number of hot flashes in each severity category multiplied by the severity score) were used as primary outcome measures. Dropout rates and the incidences of frequently reported adverse events (eg, dizziness/unsteadiness, fatigue/somnolence) were also investigated.
Results: The systematic review included 7 trials conducted in 901 patients between 2002 and 2008. Study sizes ranged from 22 to 420 patients, total daily doses of gabapentin ranged from 900 to 2400 mg, and titration periods lasted 3 to 12 days. All of the trials were conducted in North America (6 in the United States and 1 in Canada); 4 of the trials enrolled subjects with a history of breast cancer, whereas the remaining 3 trials only enrolled postmenopausal women. Four RCTs were included in the meta-analysis. Data were expressed as weighted mean difference (WMD) or relative risk (RR), with the associated 95% CI. Women assigned to gabapentin reported a significantly greater percent reduction in both the frequency of hot flashes (WMD = 23.72 [95% CI, 16.46–30.97]; P < 0.001) and the composite score (WMD = 27.26 [95% CI, 21.24–33.29]; P < 0.001), with significant between-study heterogeneity (I² = 97.8% and 95.6%, respectively). Dropouts due to adverse events were more frequent in women randomized to gabapentin than in controls (RR = 2.09 [95% CI, 1.13–3.85]; P = 0.02; I² = 0%). The risk of symptom clustering also was significantly higher in the treatment group than in the controls (dizziness/unsteadiness: RR = 6.94 [95% CI, 3.19–15.13]; P < 0.001; I² = 63.1%; and fatigue/somnolence: RR = 4.78 [95% CI, 2.23–10.25]; P < 0.001; I² = 0%).
Conclusions: Comparisons of gabapentin and placebo revealed reductions of 20% to 30% in the frequency and severity of hot flashes with gabapentin, although data across the studies were too heterogeneous to provide a reliable summary effect. Clusterings of dizziness/unsteadiness and fatigue/somnolence were the most frequently reported adverse events associated with gabapentin and resulted in a higher dropout rate due to adverse events in the gabapentin-treated patients than in the controls. More studies are needed to consolidate the outcomes and elucidate useful details regarding this treatment.
Rapid quantification of gabapentin in human plasma by liquid chromatography/tandem mass spectrometry
2006, Journal of Pharmaceutical and Biomedical Analysis
A simple, sensitive and rapid liquid chromatography/tandem mass spectrometry (LC–MS/MS) method was developed and validated for the quantification of gabapentin, a new antiepileptic drug, in human plasma using its structural analogue, 1,1-cyclohexane diacetic acid monoamide (CAM) as internal standard. The method involved a simple protein precipitation by means of acetonitrile followed by a rapid isocratic elution with 10 mM ammonium formate buffer/acetonitrile (20/80, v/v, pH 3.0) on Waters Symmetry^® C₁₈ reversed phase chromatographic column and analyzed by mass spectrometry in the multiple reaction monitoring mode. The precursor to product ion transitions of m/z 172 → 154 and m/z 200 → 182 were used to measure the analyte and the IS, respectively. The assay exhibited a linear dynamic range of 40–10 000 ng/mL for gabapentin in human plasma. The limit of detection and lower limit of quantification in human plasma were 10 and 40 ng/mL, respectively. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. A run time of 2 min for each sample made it possible to analyze a throughput of more than 400 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies.
Effect of systemic and intrathecal gabapentin on allodynia in a new rat model of postherpetic neuralgia
2005, Brain Research
Citation Excerpt :
Controlled clinical trials have demonstrated that gabapentin, an anticonvulsant, reduces neuropathic pain in patients and exhibits positive effects on mood and quality of life [1,23]. However, clinical studies on the effect of gabapentin in patients with postherpetic neuralgia have largely focused on the subjective spontaneous pain (i.e., mean daily pain scores) [21,23,25]. In this study, we quantified the effect of gabapentin on allodynia in RTX-treated rats in an attempt to further validate this animal model of postherpetic neuralgia.
Patients with postherpetic neuralgia often have an increased sensitivity to a tactile stimulus but impaired thermal sensitivity in the same affected dermatomes. We recently found that depletion of capsaicin-sensitive afferents by systemic treatment with a potent TRPV1 agonist, resiniferotoxin, in adult rats produces long-lasting paradoxical changes in mechanical and thermal sensitivities, which resemble the unique clinical features of postherpetic neuralgia. The anticonvulsant gabapentin is effective in reducing the subjective pain score in patients with postherpetic neuralgia. In this study, we quantified the potential effect of systemic and intrathecal gabapentin on tactile allodynia induced by resiniferotoxin in rats. Intraperitoneal injection of 200 μg/kg resiniferotoxin produced a rapid and sustained increase in the paw withdrawal latency to a radiant heat stimulus. Profound tactile allodynia developed in all the resiniferotoxin-treated rats within 3 weeks. Intraperitoneal injection of 30–60 mg/kg of gabapentin in resiniferotoxin-treated rats significantly increased the withdrawal threshold in response to von Frey filaments. Furthermore, intrathecal administration of 10–30 μg of gabapentin also produced a significant effect on the mechanical withdrawal threshold in all resiniferotoxin-treated rats. These data provide complementary new information that gabapentin administered systemically and spinally can effectively relieve tactile allodynia in this animal model of postherpetic neuralgia.
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Use of gabapentin for postherpetic neuralgia: Results of two randomized, placebo-controlled studies

Abstract

Pain

Pain

Pain

J Pain Symptom Manage.

Am J Med.

Pain

Diagnosing and managing shingles and PHN

Postherpetic neuralgia: A model for neuropathic pain?

Treatment of postherpetic neuralgia: An update

Drugs

Herpes zoster and postherpetic neuralgia. Optimal treatment

Drugs Aging

Gabapentin for the treatment of postherpetic neuralgia: A randomized controlled trial

JAMA

The management of postherpetic neuralgia

Postgrad Med J.

Postherpetic neuralgia—pathogenesis, treatment, and prevention

N Engl J Med.