Dexmedetomidine in Psychiatry: Repurposing of its Fast-Acting Anxiolytic, Analgesic and Sleep Modulating Properties

Abstract Drug repurposing is a strategy to identify new indications for already approved drugs. A recent successful example in psychiatry is ketamine, an anesthetic drug developed in the 1960s, now approved and clinically used as a fast-acting antidepressant. Here, we describe the potential of dexmedetomidine as a psychopharmacological repurposing candidate. This α2-adrenoceptor agonist is approved in the US and Europe for procedural sedation in intensive care. It has shown fast-acting inhibitory effects on perioperative stress-related pathologies, including psychomotor agitation, hyperalgesia, and neuroinflammatory overdrive, proving potentially useful in clinical psychiatry. We offer an overview of the pharmacological profile and effects of dexmedetomidine with potential utility for the treatment of neuropsychiatric symptoms. Dexmedetomidine exerts fast-acting and robust sedation, anxiolytic, analgesic, sleep-modulating, and anti-inflammatory effects. Moreover, the drug prevents postoperative agitation and delirium, possibly via neuroprotective mechanisms. While evidence in animals and humans supports these properties, larger controlled trials in clinical samples are generally scarce, and systematic studies with psychiatric patients do not exist. In conclusion, dexmedetomidine is a promising candidate for an experimental treatment targeting stress-related pathologies common in neuropsychiatric disorders such as depression, anxiety disorders, and posttraumatic stress disorder. First small proof-of-concept studies and then larger controlled clinical trials are warranted in psychiatric populations to test the feasibility and efficacy of dexmedetomidine in these conditions.