Jan 15, 2020
Alberto J. Espay, MD, MSc, conducts a Masterclass lecture on
treating patients with Parkinson’s-related psychosis from the
Psychopharmacology Update in Cincinnati. The meeting was
sponsored by Global
Academy for Medical Education and
Espay is professor of neurology at the University of
Cincinnati. He also serves as director of the James J. and Joan A.
Gardner Family Center Research Chair for Parkinson’s Disease and
And later, in the “Dr. RK” segment, Renee Kohanski, MD, asks you to think
about some of the complex issues tied to getting treatment for
people who are both homeless and have serious mental illness.
Treatment of Parkinson’s-related
- Psychosis related to Parkinson’s disease (PD) is a common
reason for hospitalization, institutionalization, and decline of
patients with PD. The diagnosis of PD is required before the
development of psychosis to diagnose patients with
Parkinson's-related psychosis. Parkinsonism that appears after
development of psychosis is
Lewy body dementia.
- Many factors influence the development of psychosis in PD.
Extrinsic factors include medical illnesses or metabolic
derangement causing delirium with psychosis; nonessential
dopaminergic medications such as ropinirole and
selegiline; anticholinergic medications such as benztropine,
and bladder antispasmodics; and insomnia. The last resort for
treatment of psychosis is levodopa
because patients will experience motoric decline and loss of
- There are several mechanisms for psychosis to occur via the
dopaminergic, serotonergic, and glutamatergic pathways; thus, three
neurotransmitters – serotonin, dopamine, and glutamate – can be
manipulated to treat psychosis.
Quetiapine, clozapine, and pimavanserin
are the three antipsychotics safe for use in Parkinson’s
- Clozapine is infrequently used, because of the risk of
neutropenia and required blood work monitoring, but evidence shows
that the benefits usually outweigh the risks of motor decline.
- Quetiapine is commonly used, because it has a favorable effect
on sleep and psychosis, but it negatively affects the movement
disorder of Parkinson's disease.
- Pimavanserin (Nuplazid),
the only medication
FDA approved for hallucinations and delusions associated with
psychosis in Parkinson’s disease, is highly selective for the
5-HT2A receptor as both an inverse agonist and antagonist.
- Primary adverse effects are peripheral edema and confusion, but
overall the adverse effects profile is similar to that of placebo.
In the pimavanserin clinical trials, a subset of patients worsened
and experienced more visual hallucinations. In addition,
pimavanserin can prolong the QT interval, so patients taking other
QT-prolonging medications or who have cardiac comorbidities should
be monitored with an EKG.
- Post hoc data analysis from as pivotal phase 3 study suggests
that patients with cognitive impairment and dementia may receive
more benefit from pimavanserin.
Cruz MP. Pimavanserin (Nuplazid): A treatment for hallucinations
and delusions associated with Parkinson’s disease. P T. 2017
Cummings J et al. Pimavanserin: Potential treatment for
dementia-related psychosis. J Prev Alzheimers Dis.
Huot P. 5HT2A receptors and Parkinson’s disease psychosis: A
pharmacological discussion. Neurodegenerative Disease Management.
2018 Nov 19. doi:
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