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. 2025 Feb;42(2):127-133.
doi: 10.1007/s40266-024-01170-5. Epub 2025 Jan 2.

Safety of Low-Dose Quetiapine for Insomnia in Older Adults

Rita L Hui  1 , Ashley L Lee  2 , Eric A Lee  3 , Robin S Lee  4 , Fang Niu  5
Affiliations

Safety of Low-Dose Quetiapine for Insomnia in Older Adults

Rita L Hui et al. Drugs Aging. 2025 Feb.

Abstract

Background and objective: Quetiapine is a Food and Drug Administration (FDA) approved second-generation antipsychotic. It is also commonly used at low dose for its sedative properties to treat insomnia in the older population. Quetiapine at standard doses has been associated with increased risk of cerebrovascular events, cognitive decline, and mortality in patients with dementia, especially within older adults. However, there are limited data describing its safety at lower doses, especially for the treatment of insomnia in older adults. This study aims to compare the safety of low-dose quetiapine versus trazodone or mirtazapine for insomnia in older adults in the USA.

Methods: This was a retrospective cohort study that included patients aged 65 years or older who started low-dose quetiapine, trazodone, or mirtazapine for the treatment of insomnia from October 2018 to September 2021. The primary outcome was all-cause mortality and secondary outcomes included new incidences of stroke or transient ischemic attack, dementia, and falls with or without traumatic fractures. They were identified from electronic medical records using ICD-10-CM clinical diagnosis codes. Eligible patients were followed from the initiation of the drug until death, end of target drug exposure or escalation of dose, end of health plan membership, or 30 September 30 2022, whichever came first. Patients initiated mirtazapine or trazodone were matched to each patient who initiated quetiapine at a 4:1 ratio using propensity score matching method.

Results: We included 375 patients initiated on low-dose quetiapine, who were matched to 1500 patients started on trazodone and 1500 patients started on mirtazapine. Comparing patients who received quetiapine with trazodone, the quetiapine group had an increased risk of mortality (hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.2-8.1; P < 0.05), dementia (HR 8.1, 95% CI 4.1-15.8; P < 0.05), and falls (HR 2.8, 95% CI 1.4-5.3; P < 0.05). When comparing quetiapine with mirtazapine, quetiapine group had an increased risk of dementia (HR 7.1, 95% CI 3.5-14.4; P < 0.05). No significant differences were detected in other outcomes.

Conclusions: Caution should be taken in practice when using low-dose quetiapine for insomnia in older adults. It is associated with significantly higher rates of mortality, dementia, and falls when compared with trazodone and a higher dementia rate when compared with mirtazapine.

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Conflict of interest statement

Declarations. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not for profit. Conflict of Interest: The authors have no conflicts of interest to report. The authors did not receive support from any organization for the submitted work. Ethics Approval: Ethics approval was granted for this retrospective study by the institutional review boards (IRBs) of Kaiser Permanente (KP) Northern California (NC) (IRB no. 1961885) and Kaiser Permanente (KP) Southern California (SC) (IRB no. 13347). Data Protection, Confidentiality, and Privacy: The plans for data protection, confidentiality, and privacy were reviewed and approved by the IRBs of KP NC and KP SC. Consent to Participate: This study has been approved by the IRBs of KP NC and KP SC with a waiver of informed patient consent in view of the retrospective nature of the study. Consent to Publication: Not applicable. Availability of Data and Material: The datasets generated during and/or analyzed during the current study are not authorized to be publicly available under the current ethics approval. However, any queries regarding the datasets generated and analyzed for this project may be directed to the corresponding author. Author Contributions: Authors R.L.H., A.L.L., E.A.L., R.L., and F.N. contributed to the study concept and design. R.L.H. and F.N. were responsible for data collection and analysis. The first draft of the manuscript was written by R.L.H. and A.L.L., with major edits made by F.N. and R.L.H. All authors reviewed and commented on previous versions of the manuscript and approved the final version. All authors have reviewed and approved the final submitted manuscript and agree to be accountable for its content.

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