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Pharmacology of Sleep and PTSD: Prazosin - An Alpha-1 Adrenoreceptor Antagonist Approach to Post-traumatic Stress Disorder Pharmacotherapy

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Sleep and Combat-Related Post Traumatic Stress Disorder

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Abstract

Increased brain noradrenergic activity contributes to the pathophysiology of post-traumatic stress disorder (PTSD) in a substantial proportion of patients. Prazosin is an inexpensive, clinically available and brain active drug that reduces brain noradrenergic activity by antagonizing the effects of norepinephrine at the postsynaptic alpha-1 adrenoreceptor. This chapter reviews the neurobiologic rationale and clinical trial evidence supporting efficacy of prazosin for PTSD trauma nightmares, distressed awakenings and day time hyperarousal symptoms; and provides suggestions for biomarker and clinical presentation characteristics that help identify those PTSD patients most likely to benefit from prazosin treatment. It also reviews prazosin as a potential treatment for disorders commonly comorbid with military PTSD including alcohol use disorder and post-concussion headache. Finally, suggestions are provided concerning optimizing prazosin treatment and management of the occasional adverse drug effects.

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Notes

  1. 1.

    Most CNS alpha-2 AR are presynaptic inhibitory autoreceptors; however, a modest expression of postsynaptic alpha-2 AR has been demonstrated in prefrontal cortex [49].

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Authors and Affiliations

  1. Veterans Affairs Mental Illness Research, Education and Clinical Center, Seattle, WA, USA

    Murray A. Raskind MD

  2. Psychiatry and Behavioral Sciences, University of Washington, Seattle, USA

    Murray A. Raskind MD

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  1. Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands

    Eric Vermetten

  2. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Anne Germain

  3. University of California, San Francisco, California, USA

    Thomas C. Neylan

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Raskind, M.A. (2018). Pharmacology of Sleep and PTSD: Prazosin - An Alpha-1 Adrenoreceptor Antagonist Approach to Post-traumatic Stress Disorder Pharmacotherapy. In: Vermetten, E., Germain, A., Neylan, T. (eds) Sleep and Combat-Related Post Traumatic Stress Disorder. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7148-0_30

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