Efficacy and Safety of Gabapentin and Pregabalin in Patients with Vasomotor Symptoms: a Systematic Review and Meta-Analysis

Abstract Objective Vasomotor symptoms are common among postmenopausal women and patients receiving hormone deprivation therapies, and emerging studies are exploring gabapentin’s and pregabalin’s effects as non-hormonal treatment options. We aimed to assess the efficacy and safety of these two drugs. Data sources Based on a pre-registered protocol (PROSPERO–CRD42019133650), we searched 10 databases (PubMed, Embase, Web of Science, PsycINFO, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov , CBM, CNKI, VIP and Wanfang) as well as the WHO international clinical trials registry platform and reference lists of related literatures. Study eligibility criteria Randomized controlled trials (RCT) and randomized crossover studies exploring gabapentin and pregabalin among women patients with vasomotor symptoms were included. Study appraisal and synthesis methods The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was followed. Two reviewers independently selected studies, assessed bias, and extracted data. Mean difference (MD), standardized mean difference (SMD) with 95% confidence intervals (CI) were assessed by random effects models. Heterogeneities were assessed by I2 statistics, and the quality of evidence was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Nineteen RCTs and two randomized crossover trials reporting results from 3519 participants were included. Gabapentin could reduce hot flash frequency (MD –1.62, 95%CI –1.98 to –1.26 after four weeks; MD –2.77, 95%CI –4.29 to –1.24 after 12 weeks) and composite score (SMD –0.47, 95%CI –0.71 to –0.23 after four weeks; SMD –0.77, 95%CI –1.15 to –0.40 after 12 weeks) compared with placebo. Both menopausal participants and patients with breast cancer benefited from treatment. Higher risks of dizziness and somnolence were found in the gabapentin group than in the control group (RR 4.45, 95%CI 2.50 to 7.94; RR 3.29, 95%CI 1.97 to 5.48; respectively). Estrogen was more effective in reducing hot flash frequency than gabapentin. No statistically significant difference in reduction of hot flash severity score was found between gabapentin and antidepressants. The trials comparing gabapentin or pregabalin to the other interventions were too limited to make a conclusion. Conclusions Favorable effects of gabapentin in relieving vasomotor symptoms were observed, compared to controls, but were less effective than those of estrogen. Evidence supporting the therapeutic effect of pregabalin is still lacking.