Effects of Pharmacologic Interventions on Objective Sleep Architecture and Continuity in Alzheimer’s Disease: A Network Meta-analysis of Randomized Trials
Tejaswin Mariappan1, Noorul Hidhaya S1, Gurunathan Srinivasan1, Haran Srinivasan Saravanan2, Praveen Nandha Kumar Pitchan Velammal3, Javed Ahamed Cumbum Syed4
1Stanley Medical College, Chennai, 2Government Medical College, Omandurar Government Estate, Chennai, 3UTHSC, Memphis, 4University of Michigan, Ann Arbor
Objective:
To assess pharmacologic effects on objective sleep-wake parameters in Alzheimer’s disease(AD).
Background:

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.


Design/Methods:

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.


Results:

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.


Conclusions:
Suvorexant demonstrated the most consistent efficacy, with statistical significance for increasing total sleep time, sleep efficiency and reduced wakefulness after sleep onset. Lembroxeant had modest effects on sleep efficiency, while zolpidem and zopiclone ranked highest for reducing night awakenings without statistical significance. With such therapeutic potential for enhancing sleep continuity by Suvorexant, further long-term trials could confirm sustained benefits and safety
10.1212/WNL.0000000000217303
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