Comparative Efficacy and Tolerability of Multiple Antipsychotics Across Varying Doses for Neuropsychiatric Symptoms of Dementia Including Alzheimer's Disease: A Dose–Response Model‐Based Network Meta‐Analysis

Background Antipsychotics are widely used for neuropsychiatric symptoms (NPSs) in dementia including Alzheimer's disease (AD), yet balancing efficacy and safety remains a major clinical challenge. Methods Relevant randomized controlled trials were identified through a comprehensive literature search of CENTRAL, PubMed, CINAHL, and ClinicalTrials.gov . We conducted a dose–response model‐based network meta‐analysis to evaluate the efficacy as the change in overall NPS severity and the tolerability as treatment discontinuation due to adverse events of aripiprazole, brexpiprazole, risperidone, quetiapine and olanzapine at varying doses in patients with dementia including AD. Results Twenty trials involving 5844 participants were included. Most of the included antipsychotics exhibited a generally positive dose–response relationship with respect to both efficacy and tolerability, except for olanzapine, which showed a bell‐shaped curve in terms of efficacy. Only aripiprazole 10 mg, brexpiprazole 1–2.5 mg, risperidone 1–2 mg, and olanzapine 2.5–5 mg were significantly more effective than placebo. Tolerability did not significantly decrease compared to placebo for aripiprazole up to 10 mg, brexpiprazole up to 3 mg, risperidone up to 1 mg, olanzapine up to 2.5 mg and at 15 mg, and quetiapine up to 200 mg. Furthermore, significant differences in efficacy and tolerability were observed between certain doses of several antipsychotics. Conclusions Aripiprazole 10 mg, brexpiprazole 1–2.5 mg, risperidone 1 mg, and olanzapine 2.5 mg were both effective and well tolerated, indicating their potential as favorable treatment options. As the present model incorporates several sources of uncertainty, its findings should be interpreted with caution and regarded as a provisional framework to support clinical decision‐making.