QTc Interval Prolongation with Therapies Used to Treat Patients with Parkinson’s Disease Psychosis: A Narrative Review

Yasar Torres-Yaghi, Amelia Carwin, Jacob Carolan, Steven Nakano, Fahd Amjad, Fernando Pagan Department of Neurology, National Parkinson’s Foundation Center for Excellence, Translational Neurotherapeutics Program, Movement Disorders Program, MedStar Georgetown University Hospital, Washington, DC, USACorrespondence: Yasar Torres-YaghiMedStar Georgetown University Hospital, Department of Neurology, National Parkinson’s Foundation Center for Excellence, Translational Neurotherapeutics Program, Movement Disorders Program, 3800 Reservoir Road, NW, Washington, DC, 20007, USATel +1 202-444-6087Fax +1 202-444-2186Email yasaryaghi@gmail.comAbstract: In addition to the classic motor symptoms of Parkinson’s disease (PD), people with PD frequently experience nonmotor symptoms that can include autonomic dysfunction and neuropsychiatric symptoms such as PD psychosis (PDP). Common patient characteristics, including older age, use of multiple medications, and arrhythmias, are associated with increased risk of corrected QT interval (QTc) prolongation, and treatments for PDP (antipsychotics, dementia medications) may further increase this risk. This review evaluates how medications used to treat PDP affect QTc interval from literature indexed in the PubMed and Embase databases. Although not indicated for the treatment of psychosis, dementia therapies such as donepezil, rivastigmine, memantine, and galantamine are often used with or without antipsychotics and have minimal effects on QTc interval. Among the antipsychotics, data suggesting clinically meaningful QTc interval prolongation are limited. However, many antipsychotics have other safety concerns. Aripiprazole, olanzapine, and risperidone negatively affect motor function and are not recommended for PDP. Quetiapine is often sedating, can exacerbate underlying neurogenic orthostatic hypotension, and may prolong the QTc interval. Pimavanserin was approved by the US Food and Drug Administration (FDA) in 2016 and remains the only FDA-approved medication available to treat hallucinations and delusions associated with PDP. However, pimavanserin can increase QTc interval by approximately 5– 8 ms. The potential for QTc prolongation should be considered in patients with symptomatic cardiac arrhythmias and those receiving QT-prolonging medications. In choosing a medication to treat PDP, expected efficacy must be balanced with potential safety concerns for individual patients.Keywords: QTc interval prolongation, antipsychotic agents, clozapine, quetiapine, pimavanserin