For my wife who has PD for about 16 years, cognition and psychosis is more of a problem than moving.

Plasma α-synuclein predicts cognitive decline in Parkinson's disease. - PubMed - NCBI

CONCLUSIONS:

Our data suggest that plasma α-synuclein level correlates with cognitive decline but not motor severity in patients with PD. Plasma α-synuclein could serve as a surrogate biomarker for patients at risk of cognitive decline.

Ashleyk,

If I remember correctly, isn't your wife taking Nuplazid? Is it not helping the psychosis? If not, what does the doctor recommend? Everything I have read indicates it's a real balancing act-the more levodopa you take for movement, the worse the psychosis....but if you cut back on the levodopa, moving is a real problem but there are (usually) less hallucinations. It's a lousy choice to have to make

My wife has been taking Nuplazid 34mg, Pimavanserine, for about 6 months. It seems to help somewhat for her PD psychosis but it's not dramatic. She still hallucinates and becomes difficult but it probably helps enough to keep her home. She is also on other psych meds, when she takes them. She had 16 ECT treatments last year, which even if they helped, were not worth the risk and time. The last option is clozapine which requires weekly blood tests.

Thank you for sharing this, wow is all I can say. I've heard the same thing about Nuplazid, it helps but isn't a wonder drug. And Clozapine is a benzodiazapene, which I have read should be avoided if at all possible. Not many choices: lousy and lousier.

I think it would be useful to discuss the following ideas with your doctors.

Keep a diary of the symptoms and relate that to the peaks and troughs of the daily drug regimen. For instance, is the psychosis absent before the first dose of the day, but present a hour after the dose?

A paper by Latoo et al. gives some pointers of how to continue [1]:

"The main extrinsic cause of Parkinson’s disease psychosis is thought to be the medication used to treat the condition ... , although levodopa and catechol-O-methyl transferase (COMT) inhibitors are implicated to a lesser extent than other drugs."

I take this to mean that one should withdraw first agonists, possibly replacing them with levodopa to make up for any motor deficiencies (see posts on levodopa equivalent dose for conversion factors). It may be possible to get some extra benefit from using a COMT inhibitor such as entacapone (Stalevo = levodopa/carbidopa/entacapone). A further benefit may come from smoothing out levodopa plasma levels by taking into account the pharmacokinetic properties of levodopa. Possibly, by reducing the dose, while increasing its frequency.

Reference:

[1] "Diagnosis and management of psychosis in Parkinson’s disease"
Javed Latoo MBBS, DPM, MRCPsych, Minal Mistry BM, BSc, MRCPsych, MSc, PGDipEd, Francis J Dunne MRCPsych, FRCPsych
Progress in Neurology and Psychiatry
Volume 16, Issue 5, Version of Record online: 12 OCT 2012
Diagnosis and management of psychosis in Parkinson's disease - Latoo - 212 - Progress in Neurology and Psychiatry - Wiley Online Library

John