Wake-Promoting Pharmacotherapy for Psychiatric Disorders


Medications promoting wakefulness are currently used in psychopharmacology in different contexts and with different objectives. In particular, they may be used for the treatment of syndromes that primarily show significant impairment in alertness/wakefulness (e.g., excessive sleepiness and other sleep disorders) as well as for the symptomatic treatment of different neuropsychiatric disorders that, in turn, are not exclusively characterized by sleep-wake disturbances (like mood disorders, for instance). In addition, several psychotropic compounds, including some antipsychotics, mood stabilizers, antidepressants, and anxiolytics have well-established sedating side effects that may go beyond the therapeutic target and require the symptomatic use of wake-promoting agents. Even though such a clinical scenario reflects millions of individuals affected (alterations of wakefulness have a prevalence rate of 20–43 % in the general population), relatively few pharmacotherapies are available, mainly including compounds with psychostimulating effects, such as methylphenidate, modafinil, and armodafinil and some amphetaminic agents. In light of their side effects and potential for abuse, such compounds have received FDA approval only for a limited number of psychiatric disorders. Nonetheless, their clinical application has recently become more widespread, including attention deficit hyperactivity disorder, narcolepsy, treatment-resistant depression, bipolar disorder, shift work sleep disorder, schizophrenia, and addictions. Wake-promoting agents have different mechanisms of action, peculiar clinical strengths and specific limitations, with novel drugs in the field under extensive investigation. The present review is aimed to provide an updated overview of the aforementioned compounds as well as investigational drugs in the field, in terms of mechanism of action, indications and use in clinical practice.

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Compliance With Ethics Guidelines

Conflict of Interest

Cristina Dobrea, Laura Cremaschi and Chiara Arici declare that they have no conflict of interest.

Bernardo Dell’Osso has been part of the Speaker Bureau of Astra Zeneca, Bristol Myers Squibb, Janssen-Cilag, Eli Lilly, Pfizer, Glaxo Smith Kline, Lundbeck, Cyberonics and Italfarmaco.

A. Carlo Altamura is a consultant for Roche, Merck, Astra Zeneca, Bristol Myers Squibb, Janssen-Cilag, Lundbeck, Sanofi, Eli Lilly and Pfizer.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Correspondence to Bernardo Dell’Osso.

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This article is part of the Topical Collection on Sleep Disorders

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Dell’Osso, B., Dobrea, C., Cremaschi, L. et al. Wake-Promoting Pharmacotherapy for Psychiatric Disorders. Curr Psychiatry Rep 16, 524 (2014). https://doi.org/10.1007/s11920-014-0524-2

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  • Wake-promoting agents
  • Stimulants
  • Neuropsychiatric disorders