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Trazodone improves obstructive sleep apnea after ischemic stroke: a randomized, double-blind, placebo-controlled, crossover pilot study

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Abstract

Background

Low arousal threshold plays a part in the pathogenesis of obstructive sleep apnea (OSA) and may be improved by sedatives. Sedative antidepressants are frequently prescribed for stroke patients due to their high prevalence of insomnia and depression. However, the effect of sedative antidepressants on the severity of OSA in stroke patients has not been studied well.

Methods

In a double-blinded randomized crossover pilot study, 22 post-acute ischemic stroke patients (mean age, 61.7 ± 10.6 y) with OSA received 100 mg of trazodone or a placebo just before polysomnography, with approximately 1 week between measures. The study also measured baseline heart rate variability and 24-h ambulatory blood pressure.

Results

Administration of trazodone significantly increased the percentage time of slow-wave sleep (31.5 ± 13.2 vs. 18.4 ± 8.7%; P < 0.001) and improved almost all the parameters of OSA severity, including the apnea–hypopnea index (AHI, 25.4 ± 15.4 vs. 39.1 ± 18.4 events/h; P < 0.001), the respiratory arousal index (9.8 (5.8–11.95) vs. 14.1 (11.3–18.7) events/h; P < 0.001), and the minimum oxygen saturation (80.2 ± 9.1 vs. 77.1 ± 9.6%; P = 0.016). Responders to therapy (AHI reduced by > 50%; n = 7/22) had predominant OSA during rapid-eye-movement sleep and decreased sympathetic tone, as reflected in significantly lower mean blood pressure, diastolic blood pressure, and normalized low-frequency power.

Conclusions

Obstructive sleep apnea with comorbid ischemic stroke may be a distinctive phenotype which responds quite well to trazodone, decreasing OSA severity without increasing nocturnal hypoxia.

Trial Registration

Clinicaltrials.gov: NCT04162743, 2019/11/10.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

Study funded by the Chang Gung Medical Research Council under Contract No. CMRPG2I0021.

Author information

Authors and Affiliations

  1. Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung, Taiwan

    Chung-Yao Chen

  2. Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taiwan

    Chia-Ling Chen

  3. Graduate Institute of Early Intervention, College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Chia-Ling Chen

  4. School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Chung-Yao Chen & Chung-Chieh Yu

  5. Division of Pulmonary Critical Care and Sleep Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan

    Chung-Chieh Yu

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  1. Chung-Yao Chen
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Correspondence to Chung-Yao Chen.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Chang Gung Medical Foundation.

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Informed consent was obtained from all participants and/or their legal guardians.

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Patients signed informed consent regarding publishing their data and photographs.

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Cite this article

Chen, CY., Chen, CL. & Yu, CC. Trazodone improves obstructive sleep apnea after ischemic stroke: a randomized, double-blind, placebo-controlled, crossover pilot study. J Neurol 268, 2951–2960 (2021). https://doi.org/10.1007/s00415-021-10480-2

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  • DOI: https://doi.org/10.1007/s00415-021-10480-2

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