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Different doses of gabapentin formulations for postherpetic neuralgia: A systematical review and meta-analysis of randomized controlled trials.
J Dermatolog Treat 2017; 28(1):65-77JD

Abstract

WHAT IS KNOWN AND OBJECTIVE

Gabapentin, extended-release gabapentin (gabapentin ER), and gabapentin enacarbil (GEn), play an important role in relieving pain associated with postherpetic neuralgia (PHN). Although previous systematic reviews have assessed the efficacy and safety of gabapentin formulations for PHN, they have failed to take formulation differences and dose differences into account. Aiming at assessing the efficacy and safety of different doses of gabapentin formulations for PHN, this study performed a systematical review and meta-analysis of randomized controlled trials (RCTs).

METHODS

Electronic databases (PubMed, EBSCO, Ovid MEDLINE, and Web of Science) were systematically searched by terms of "gabapentin [Title/Abstract] AND postherpetic neuralgia [Title/Abstract]" from the year 1966 to present. Efficacy measurements were changes in average daily pain (ADP) scores, sleep interference scores, at least 50% reduction in pain intensity, and changes in Patient/Clinician Global Impression of Change (PGIC/CGIC) from baseline to the end of treatment. Safety measures were the proportion of patients suffering from any adverse event, dizziness, somnolence, and peripheral edema. Outcomes for continuous data and dichotomous data were estimated with standard mean difference (SMD) and risk ratio (RR), respectively.

RESULTS AND DISCUSSION

Seven RCTs encompassing 2041 randomized participants for efficacy assessment and 2050 randomized participants for safety assessment were identified. Gabapentin formulations in reducing ADP scores (the primary outcomes) were as follows: gabapentin 3600 mg/day, SMD: -0.86; 95% CI: -1.13, -0.58; p < 0.00001; gabapentin ER 1800 mg/day once daily, SMD: -0.21; 95% CI: -0.42, -0.01; p = 0.04; gabapentin ER 1800 mg/day twice daily, SMD: -0.25; 95% CI: -0.57, 0.06; p = 0.12; GEn 1200 mg/day, SMD: -0.43; 95% CI: -0.66, -0.20; p = 0.0002; GEn 2400 mg/day, SMD: -0.33; 95% CI: -0.62, -0.03; p = 0.03; GEn 3600 mg/day, SMD: -0.50; 95% CI: -0.79, -0.20; p = 0.0009. In addition, gabapentin from 1800 to 3600 mg/day doses could significantly improve sleep interference, at least 50% reduction in pain intensity and PGIC/CGIC, but highly increased the incidence of any adverse event, dizziness, somnolence and peripheral edema with an increasing dose. Gabapentin ER 1800 mg/day once daily treatment could not only effectively relieve PHN pain but also significantly increase the risk of adverse events, while twice daily treatment almost showed no significant pharmacological effect and adverse events. GEn at doses of 1200 mg/day and 2400 mg/day were safe in decreasing any adverse event (1200 mg/day, RR = 1.08, 95% CI: 0.91, 1.29, p = 0.38; 2400 mg/day, RR = 1.18, 95% CI: 0.98, 1.41, p = 0.08), dizziness (1200 mg/day, RR = 1.86, 95% CI: 0.58, 6.01, p = 0.30; 2400 mg/day, RR = 1.74, 95% CI: 0.95, 3.19, p = 0.07), and somnolence (1200 mg/day, RR = 1.22, 95% CI: 0.51, 2.91, p = 0.65; 2400 mg/day, RR = 1.30, 95% CI: 0.53, 3.22, p = 0.57). GEn 3600 mg/day could only increase the risk of any adverse event (RR = 1.23, 95% CI: 1.03, 1.47, p = 0.02) and dizziness (RR = 2.03, 95% CI: 1.13, 3.63, p = 0.02).

WHAT IS NEW AND CONCLUSION

An increasing gabapentin dose may not provide a good pharmacological therapy, whereas it can increase the risk of adverse events. Gabapentin ER, 1800 mg/day once daily treatment is significantly effective in pain relief, following high incidence of adverse events, but twice daily treatment shows no significant differences in both efficacy and safety compared with placebo. GEn 1200 mg/day and 2400 mg/day doses are more effective and safe in treating PHN. The long-term efficacy and safety of different doses of gabapentin formulations remain to be determined.

Authors+Show Affiliations

a Department of Dermatology , the Affiliated Provincial Hospital of Anhui Medical University , Hefei , China.b Department of Neurology , the Affiliated Provincial Hospital of Anhui Medical University , Hefei , China.

Pub Type(s)

Journal Article
Meta-Analysis
Review

Language

eng

PubMed ID

27798973

Citation

Wang, Juan, and Yuyou Zhu. "Different Doses of Gabapentin Formulations for Postherpetic Neuralgia: a Systematical Review and Meta-analysis of Randomized Controlled Trials." The Journal of Dermatological Treatment, vol. 28, no. 1, 2017, pp. 65-77.
Wang J, Zhu Y. Different doses of gabapentin formulations for postherpetic neuralgia: A systematical review and meta-analysis of randomized controlled trials. J Dermatolog Treat. 2017;28(1):65-77.
Wang, J., & Zhu, Y. (2017). Different doses of gabapentin formulations for postherpetic neuralgia: A systematical review and meta-analysis of randomized controlled trials. The Journal of Dermatological Treatment, 28(1), pp. 65-77. doi:10.3109/09546634.2016.1163315.
Wang J, Zhu Y. Different Doses of Gabapentin Formulations for Postherpetic Neuralgia: a Systematical Review and Meta-analysis of Randomized Controlled Trials. J Dermatolog Treat. 2017;28(1):65-77. PubMed PMID: 27798973.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Different doses of gabapentin formulations for postherpetic neuralgia: A systematical review and meta-analysis of randomized controlled trials. AU - Wang,Juan, AU - Zhu,Yuyou, Y1 - 2016/11/01/ PY - 2016/11/2/pubmed PY - 2017/4/5/medline PY - 2016/11/2/entrez KW - Gabapentin KW - efficacy KW - meta-analysis KW - postherpetic neuralgia KW - safety SP - 65 EP - 77 JF - The Journal of dermatological treatment JO - J Dermatolog Treat VL - 28 IS - 1 N2 - WHAT IS KNOWN AND OBJECTIVE: Gabapentin, extended-release gabapentin (gabapentin ER), and gabapentin enacarbil (GEn), play an important role in relieving pain associated with postherpetic neuralgia (PHN). Although previous systematic reviews have assessed the efficacy and safety of gabapentin formulations for PHN, they have failed to take formulation differences and dose differences into account. Aiming at assessing the efficacy and safety of different doses of gabapentin formulations for PHN, this study performed a systematical review and meta-analysis of randomized controlled trials (RCTs). METHODS: Electronic databases (PubMed, EBSCO, Ovid MEDLINE, and Web of Science) were systematically searched by terms of "gabapentin [Title/Abstract] AND postherpetic neuralgia [Title/Abstract]" from the year 1966 to present. Efficacy measurements were changes in average daily pain (ADP) scores, sleep interference scores, at least 50% reduction in pain intensity, and changes in Patient/Clinician Global Impression of Change (PGIC/CGIC) from baseline to the end of treatment. Safety measures were the proportion of patients suffering from any adverse event, dizziness, somnolence, and peripheral edema. Outcomes for continuous data and dichotomous data were estimated with standard mean difference (SMD) and risk ratio (RR), respectively. RESULTS AND DISCUSSION: Seven RCTs encompassing 2041 randomized participants for efficacy assessment and 2050 randomized participants for safety assessment were identified. Gabapentin formulations in reducing ADP scores (the primary outcomes) were as follows: gabapentin 3600 mg/day, SMD: -0.86; 95% CI: -1.13, -0.58; p < 0.00001; gabapentin ER 1800 mg/day once daily, SMD: -0.21; 95% CI: -0.42, -0.01; p = 0.04; gabapentin ER 1800 mg/day twice daily, SMD: -0.25; 95% CI: -0.57, 0.06; p = 0.12; GEn 1200 mg/day, SMD: -0.43; 95% CI: -0.66, -0.20; p = 0.0002; GEn 2400 mg/day, SMD: -0.33; 95% CI: -0.62, -0.03; p = 0.03; GEn 3600 mg/day, SMD: -0.50; 95% CI: -0.79, -0.20; p = 0.0009. In addition, gabapentin from 1800 to 3600 mg/day doses could significantly improve sleep interference, at least 50% reduction in pain intensity and PGIC/CGIC, but highly increased the incidence of any adverse event, dizziness, somnolence and peripheral edema with an increasing dose. Gabapentin ER 1800 mg/day once daily treatment could not only effectively relieve PHN pain but also significantly increase the risk of adverse events, while twice daily treatment almost showed no significant pharmacological effect and adverse events. GEn at doses of 1200 mg/day and 2400 mg/day were safe in decreasing any adverse event (1200 mg/day, RR = 1.08, 95% CI: 0.91, 1.29, p = 0.38; 2400 mg/day, RR = 1.18, 95% CI: 0.98, 1.41, p = 0.08), dizziness (1200 mg/day, RR = 1.86, 95% CI: 0.58, 6.01, p = 0.30; 2400 mg/day, RR = 1.74, 95% CI: 0.95, 3.19, p = 0.07), and somnolence (1200 mg/day, RR = 1.22, 95% CI: 0.51, 2.91, p = 0.65; 2400 mg/day, RR = 1.30, 95% CI: 0.53, 3.22, p = 0.57). GEn 3600 mg/day could only increase the risk of any adverse event (RR = 1.23, 95% CI: 1.03, 1.47, p = 0.02) and dizziness (RR = 2.03, 95% CI: 1.13, 3.63, p = 0.02). WHAT IS NEW AND CONCLUSION: An increasing gabapentin dose may not provide a good pharmacological therapy, whereas it can increase the risk of adverse events. Gabapentin ER, 1800 mg/day once daily treatment is significantly effective in pain relief, following high incidence of adverse events, but twice daily treatment shows no significant differences in both efficacy and safety compared with placebo. GEn 1200 mg/day and 2400 mg/day doses are more effective and safe in treating PHN. The long-term efficacy and safety of different doses of gabapentin formulations remain to be determined. SN - 1471-1753 UR - https://www.unboundmedicine.com/medline/citation/27798973/Different_doses_of_gabapentin_formulations_for_postherpetic_neuralgia:_A_systematical_review_and_meta_analysis_of_randomized_controlled_trials_ L2 - http://www.tandfonline.com/doi/full/10.3109/09546634.2016.1163315 DB - PRIME DP - Unbound Medicine ER -