Costello, Harry; Husain, Masud; Roiser, Jonathan P; (2024) Apathy and Motivation: Biological Basis and Drug Treatment. Annual Review of Pharmacology and Toxicology , 64 (1) 10.1146/annurev-pharmtox-022423-014645. (In press).

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Abstract

Apathy is a disabling syndrome associated with poor functional outcomes that is common across a broad range of neurological and psychiatric conditions. Currently, there are no established therapies specifically for the condition, and safe and effective treatments are urgently needed. Advances in the understanding of motivation and goal-directed behavior in humans and animals have shed light on the cognitive and neurobiological mechanisms contributing to apathy, providing an important foundation for the development of new treatments. Here, we review the cognitive components, neural circuitry, and pharmacology of apathy and motivation, highlighting converging evidence of shared transdiagnostic mechanisms. Though no pharmacological treatments have yet been licensed, we summarize trials of existing and novel compounds to date, identifying several promising candidates for clinical use and avenues of future drug development.

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