Comparative Efficacy of Elinzanetant Versus Other Non‐Hormonal Pharmaceutical Therapies for the Treatment of Moderate‐to‐Severe Vasomotor Symptoms Associated With Menopause: A Network Meta‐Analysis

BACKGROUND: Elinzanetant, a novel, dual neurokinin-targeted therapy, has been approved in various geographies for the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause. OBJECTIVE: To compare the efficacy of elinzanetant with non-hormonal pharmaceutical treatments (nHT) in alleviating VMS. SEARCH STRATEGY: A systematic literature review of Medline, Embase, and Cochrane databases identified randomised controlled trials (RCTs) published up to October 2025. SELECTION CRITERIA: RCTs of nHT in women with moderate-to-severe VMS not induced by medical treatment, reporting week 12 results for VMS frequency and severity, sleep disturbances, and quality of life. DATA COLLECTION AND ANALYSIS: Treatments were compared using a Bayesian network meta-analysis to obtain mean differences (MD) or odds ratios (OR) with 95% credible intervals. MAIN RESULTS: Of 17 included RCTs, three assessed elinzanetant 120 mg, two paroxetine 7.5 mg (PRX), four gabapentin 1200-1800 mg (GABA), three fezolinetant 45 mg (FEZO), and five desvenlafaxine 50-200 mg (DVS). Elinzanetant significantly reduced daily VMS frequency versus PRX (MD: -2.11 [-3.31, -0.92]), DVS (MD: -2.77 to -1.72), and GABA (MD: -2.22 to -2.31). The proportion of patients with ≥ 50% reduction in VMS frequency was significantly greater with elinzanetant than DVS 100 mg (OR:1.52 [1.03, 2.24]) and PRX (OR:2.20 [1.49, 3.28]), and comparable to DVS 150 mg and FEZO. Elinzanetant significantly reduced VMS severity versus DVS 50 mg (MD: -0.37 [-0.56, -0.17]) and was comparable with other assessed treatments. Elinzanetant reduced nighttime awakenings significantly more effectively than PRX (MD: -0.82 [-1.26, -0.39]) and all DVS regimens. Elinzanetant significantly improved sleep disturbance (PROMIS SD-SF-8b) score versus FEZO (MD: -2.67 [-3.92, -1.42]). Change in MENQoL did not differ significantly. CONCLUSIONS: In this indirect comparison, elinzanetant showed superior or comparable efficacy to NKT or nHT in reducing the frequency and severity of VMS, along with improving sleep disturbances, supporting its role in VMS management.