Progress in Pharmacologic Management of Neuropsychiatric Syndromes in Neurodegenerative Disorders

Importance Neuropsychiatric syndromes (NPSs) are common in neurodegenerative disorders (NDDs); compromise the quality of life of patients and their care partners; and are associated with faster disease progression, earlier need for nursing home care, and poorer quality of life. Advances in translational pharmacology, clinical trial design and conduct, and understanding of the pathobiology of NDDs are bringing new therapies to clinical care. Observations Consensus definitions have evolved for psychosis, agitation, apathy, depression, and disinhibition in NDDs. Psychosocial interventions may reduce mild behavioral symptoms in patients with NDD, and pharmacotherapy is available for NPSs in NDDs. Brexpiprazole is approved for treatment of agitation associated with Alzheimer disease dementia, and pimavanserin is approved for treatment of delusions and hallucinations associated with psychosis of Parkinson disease. Trials are being conducted across several of the NDDs, and a variety of mechanisms of action are being assessed for their effect on NPSs. Conclusions and Relevance Detection and characterization of NPSs in patients with NDDs is the foundation for excellent care. New definitions for NPSs in NDDs may inform choices regarding clinical trial populations and translate into clinical practice. Psychosocial and pharmacologic therapies may reduce behavioral symptoms and improve quality of life for patients and caregivers. Approved agents may establish regulatory precedents, demonstrate successful trial strategies, and provide the foundation for further advances in treatment development.