Advances in Management of Psychosis in Neurodegenerative Diseases

Kasia Gustaw Rothenberg, Ryan Rajaram

Psychosis is broadly defined as a disengagement from reality. It describes syndromes that impair both thought content and thought process. Psychosis negatively impacts an individual's quality of life, in addition to the families caring for them. Psychosis with different types of hallucinations and delusions occurs in the context of delirium. Neuropsychiatric symptoms (NPS) are almost universal in the course of common neurodegenerative disorders (NDD) like Alzheimer's disease (AD) or Parkinson's disease (PD). In this paper, the authors took an effort to characterize AD and PD psychosis with a special focus on the most diagnostically reliable features. Effectiveness and limitations of pharmacological interventions are discussed. Consensus diagnostic criteria have evolved for psychosis secondary to AD as well as psychosis in PD. Psychotropic medications can be effective in the treatment of NPS in NDD; however, clinicians must be mindful of the side effects. There is a consensus on benefit of initiating any acetylcholinesterase inhibitor (ACHI: donepezil, rivastigmine, and galantamine) as a first line of treatment for psychosis in AD, as it may reduce and/or avoid the need for the use antipsychotics. Pimavanserin, a selective-serotonin inverse agonist that preferentially targets 5-HT2A receptors, while avoiding activity at dopamine and other receptors commonly targeted by antipsychotics had recently been approved by FDA to treat hallucinations and delusions in PD. Quetiapine is widely prescribed for the treatment of psychosis in different NDD, but the data remains equivocal. Psychosis with different types of hallucinations and delusions may occur in the context of delirium and is almost universal as a neuropsychiatric symptom in the course of PD and AD. Currently, pimavanserin remains the only pharmacologic agent approved for treatment of psychosis in PD. In cases of other NPS in other than Parkinson's diseases, atypical antipsychotics are commonly used off-label. More research is greatly needed to advance this field and address NPS especially psychosis in geriatric population.