Endocrine Abstracts

Context: Evidence suggests that gabapentin, a γ-aminobutyric acid analogue, is effective in the treatment of hot flushes in women with natural or tamoxifen-induced menopause.

Objective and design: To investigate the efficacy and tolerability of gabapentin for the treatment of menopausal hot flushes, a systematic review of all pertinent trials and a meta-analysis of those that were randomized placebo-controlled (RCT) were performed.

Data sources and extraction: Literature search was conducted independently by two reviewers through MEDLINE, EMBASE, CENTRAL (all three from inception to June 2008); the perusal of references from relevant studies; a personal contact with experts. Percent (%) change in hot flush frequency and composite score were used as primary outcome measures. Dropout rates and incidence of common adverse effects, such as dizziness, somnolence and fatigue, were also investigated. Seven trials, reporting data on 821 subjects, were reviewed and four RCTs included in the meta-analysis.

Data synthesis: Women assigned to gabapentin demonstrated a significantly greater percent (%) reduction in both hot flush frequency (WMD (95% CI)=23.7 (16.5 to 31.0), P<10⁻⁶) and composite score (WMD (95% CI)=27.3 (21.2 to 33.2), P<10⁻⁶), yet with significant between-study heterogeneity (I²=97.8 and 95.6%, respectively). Dropouts due to adverse effects were more frequent in women randomized to gabapentin compared to controls (Relative Risk (RR) (95% CI)=2.1 (1.1 to 3.9), P=0.02, I²=0%). Risk of ‘dizziness/unsteadiness’ and ‘fatigue/somnolence’ clusterings was also found significantly higher in the treatment group (RR (95% CI)=6.9 (3.2 to 15.1), P<10⁻⁶, I²=63.1% and RR (95% CI)=4.8 (2.2 to 10.3), P<10⁻⁴, I²=0%, respectively).

Conclusions: A 20–30% reduction in hot flushes frequency and severity could be anticipated with the use of gabapentin compared to placebo, although data across studies seem too heterogeneous to provide a reliable summary effect. Further investigation is needed to provide conclusive evidence. The clusterings of dizziness/unsteadiness and fatigue/somnolence are the more common adverse effects associated with gabapentin, that can lead to reduced compliance.