Sleep disruption following neurodegeneration of the sleep regulatory pathways in AD is tackled with pharmacological interventions which target the neurotransmitters to improve sleep quality. Due to the limited evidence on the relative efficacy of various interventions, evaluation with polysomnography and actigraphy enables comparative efficacy assessment across drug classes in AD.

We performed a systematic review and meta-analysis following PRISMA guidelines. Suitable studies were identified through a comprehensive search performed across major databases up to September 2025. Data were analyzed using R with netmeta, gemtc, BUGSnet and bnma. Both frequentist and Bayesian methods were employed to indirectly measure the efficacy using random models.

Among 11 RCTs evaluating various drugs, only suvorexant 10 mg significantly increased total sleep time compared with placebo (MD 28.4 min[0.1,46.7]). SUCRA ranked suvorexant highest for suvorexant(82.6%) followed by Melatonin 8.5 mg(77.7%). Improvement in sleep efficiency was statistically significant for Suvorexant (MD 5.8 [1.99,9.61]) and numerically significant for Lemborexant(2.5-5 mg). Suvorexant ranked the highest(80.3%), followed by Lemborexant. Marked reduction in sleep latency was achieved by Suvorexant(78.7%), though not statistically significant. Reduction in wakefulness after sleep onset was statistically significant with Suvorexant with MD -17.3 min[-30.1,-4.1] and was ranked next to Zopiclone 7.5mg and Zolpidem 10 mg. Though none attained statistical significance in reducing night wake bouts, zopiclone(75.6%) and zolpidem(70.9%) were ranked highest.