Treatment of Psychosis and Dementia in Parkinson’s Disease

Parkinson’s disease (PD) has been increasingly recognized as having a multitude of nonmotor symptoms including psychosis, cognitive impairment and dementia, mood disturbances, fatigue, apathy, and sleep disorders. Psychosis and dementia, in particular, greatly affect quality of life for both patients and caregivers and are associated with poor outcomes. Safe and effective treatment options for psychosis and dementia in PD are much needed. Antipsychotics with dopamine-blocking properties can worsen parkinsonian motor features and have been associated with increased morbidity and mortality in elderly, dementia patients. For treating PD psychosis, a first step would be eliminating confounding variables, such as delirium, infections, or toxic-metabolic imbalances, followed by simplifying parkinsonian medications as tolerated. If additional treatment is warranted after such interventions, clozapine or quetiapine can be implemented at the low dose levels typically needed by PD patients. Although quetiapine is easy-to-use in clinical settings, does not require blood count monitoring like clozapine, and is anecdotally beneficial, it remains “investigational” in evidence-based medicine reviews. Though not currently available, the novel 5-HT2a inverse agonist, pimavanserin has shown promise in the treatment of PD psychosis. Current treatments for PD dementia are mostly derived from those utilized in Alzheimer’s disease, focusing mainly on cholinesterase inhibitors and memantine, a NMDA receptor antagonist. Rivastigmine, the only Food and Drug Administration approved medication for PD dementia, is a reasonable first choice. Other cholinesterase inhibitors and memantine have not yet achieved recommendation status in evidence-based medicine reviews but are well tolerated in studies of PD dementia patients. At present, there are no approved treatments for mild cognitive impairment in PD, but rasagiline, a selective MAO-B inhibitor, and atomoxetine, a serotonin norepinephrine reuptake inhibitor, have been recently studied. Nonpharmacological interventions, including cognitive therapy, physical activity, music and art therapy, and noninvasive brain stimulation techniques, may be promising options for PD cognitive impairment but await rigorous study.