looks helpful

A New Perspective in the Treatment of Parkinson’s Disease Psychosis | Touch Neurology | Independent Insight for Medical Specialists

We were offered this drug, and are taking it as part of a two-month trial. We were told it takes two months to see a difference. I have read that for many PWP, it has worked wonders, and I was hoping we would be in that category. Unfortunately, it doesn't seem to be helping us. We hallucinate every day, multiple times a day, with delusions thrown in for good measure. Day, night, light, dark, makes no difference. There hasn't been any reduction in the hallucinations and they are actually more frequent, as in, all the time. Would things be worse if we weren't taking Nuplazid? Hard to know, but for $2000.00+ a month, I would expect to see some kind of improvement. Also, FYI, you cannot get this drug just anywhere: it has to be a specialty pharmacy and they are very few and far between, so they ship you the drug.

When our two months' trial is up, we will not continue taking this drug. I think the New York Times had an article about Nuplazid and if I remember correctly, the article was cautioning against too much hope being placed in the drug. Do your research so that your expectations are realistic. Some people do great on it, others not, and still others do well but cannot afford to take it: even with insurance it might run $900.00/month. That's a lot of bread and butter

My wife has PD going on 13? years now. Seven years ago she was having "visions with insight", meaning she saw funny animals but knew they weren't real. This is not a good symptom because it probably means moving into full psychosis as the years ago by. My wife now is fully psychotic, she thinks I have girl friends, "people" are in her house doing all sorts of bad things, etc. The police and ems know her well.
Early this year she was started on 34 mg of Nuplazid (pimervancern). She took it for about 3 months but was still delusional, her actual PD may have improved. Both her neurologist and psychiatrist thought Nuplazid was not worth taking and discontinued it but increased her Geodone. She has been off of Nuplazid for about 6 weeks now and her psychosis is maybe much worse. She can be very combative and totally difficult. I restarted her on Nuplazid about 5 days ago. If she takes the pills, which often she doesn't, we will know maybe in 6 weeks if they help. Right now, we are close to looking for a nursing home for her, she is 68. Also, my co-pay for 1 month is $40. Wonder what happens when Trump gets his great, great health plan?
Also, I believe Nuplazid is a serotonin receptor blocker? If that's the case, here is a paper on Trazadone which is also in the same category? The other drug mentioned,DBM, is similar to Curcumin. They both seem to be very neuro protective if taken at the right dosage.

Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in mice | Brain | Oxford Academic
In this study, we found that both trazodone and DBM inhibited the effects of UPR activation and eIF2α phosphorylation, reversing translational attenuation and lowering levels of ATF4 and CHOP in mammalian cells (Figs 1A and 2B). This occurred without lowering eIF2α-P levels in vitro (Fig. 2B), and in vivo (Figs 3H and 4G), as has been described for ISRIB (Halliday et al., 2015; Sekine et al., 2015; Sidrauski et al., 2015). Both trazodone and DBM prevented eIF2α-P from lowering ternary complex levels, due to their ability to reduce ATF4 5’UTR regulation of luciferase (Fig. 2D), but this was via an independent mechanism than that of ISRIB (Supplementary Fig. 2).
Based on their ability to reverse UPR activation, trazodone and DBM were predicted to be potential therapeutic candidates for neurodegenerative disorders. Indeed, both compounds were found to be substantially neuroprotective in two different mouse models of neurodegeneration, prion disease and the rTg4510 tauopathy model of FTD. Both drugs showed beneficial neuroprotective effects similar to those of the experimental compounds GSK2606414 and ISRIB. Importantly, in both models, the drugs were first administered at a stage of early but established disease, equivalent to early symptomatic human disease—from 7 weeks post-infection in prion-disease mice and from 4 months of age in tauopathy mice. Treatment with each drug prevented neuronal loss in the hippocampus (Fig. 3B and C) and confirmatory neurological clinical signs (Table 1) in the majority of prion-infected mice, also restoring memory and preventing behavioural decline associated with prion infection (Fig. 3D and E). In tauopathy mice, both drugs were strongly protective against the marked hippocampal neuronal loss and forebrain atrophy that is a feature of this mouse model (Fig. 4B and C). These mice were also devoid of clinical signs of neurodegeneration. There was also significant increase in lifespan of prion-infected mice treated with trazodone or DBM (Fig. 3F), although this was more modest than was expected considering the neuroprotection observed, due to coincidental weight loss requiring early sacrifice of otherwise entirely healthy animals (Fig. 3G). This weight loss was not caused by trazodone or DBM (Figs 3G and 4F), which, critically, were also devoid of pancreatic toxicity [Figs 3B(ix–xii), 4B(xiii–xvi) and Supplementary Fig. 2), likely because both compounds only partially reverse eIF2α-P-mediated translational attenuation (Fig. 1A and B), which is associated with lack of toxicity to secretory tissue (Halliday et al., 2015). Thus, neither trazodone nor DBM suffer from the shortcomings of GSK2606414 and ISRIB: they are non-toxic to the pancreas and have favourable pharmacokinetic properties. Critically, however, they share the benefits of GSK2606414 and ISRIB, being markedly neuroprotective.
Interestingly, another unanticipated and previously unreported action of trazodone was to lower phosphorylated (p)-tau levels in rTg4510 mice (Fig. 4B, E and Supplementary Fig. 4). P-tau is associated with Alzheimer’s disease pathology and with the tauopathies FTD and progressive supranuclear palsy, and is in itself an intense focus for Alzheimer’s therapeutics. This additional effect of trazodone could be considered a desirable bonus in the treatment of these disorders. UPR activation is known to induce tau phosphorylation via activation of GSK3β (Nijholt et al., 2013) and treatment with the PERK inhibitor GSK2606414 also lowers tau phosphorylation (van der Harg et al., 2014; Radford et al., 2015). Trazodone was also able to inhibit GSK3β (Supplementary Fig. 4). However, the similar degree of neuroprotection afforded by trazodone and DBM (Table 1, Figs 3B, C, 4B and C) suggests that reduction of the stress response downstream of eIF2α-P and partial restoration of protein synthesis is the primary driver of neuroprotection in both tauopathy and prion-diseased mice. This is irrespective of sustained high levels of misfolded protein, both prion (Fig. 3J) and p-tau (in DBM treated mice; Fig. 4B and E), further demonstrating the central role the UPR plays in neurodegeneration.
In conclusion, we selected trazodone and DBM as potential therapeutic agents in neurodegenerative disease, based on their consistent ability to inhibit UPR/ISR-induced translational repression, rather than target disease-specific misfolded proteins, in organisms ranging from nematodes, through mammalian cell models, to different mouse models of neurodegeneration. The two drugs were markedly neuroprotective in both prion-diseased and FTD mice at clinically relevant doses over a sustained treatment period. These drugs therefore represent an important step forward in the pursuit of disease-modifying treatments for Alzheimer’s and related disorders. Trazodone in particular, is already licensed for use in elderly patients. These drugs should now be tested in clinical trials in the treatment of dementia.

We were told Nuplazid is a serotonin blocker, which is good because it doesn't negate the levodopa needed to move. What dose would one need to take Trazodone to equal Nuplazid?

I understand Trazodone is an old antidepressant which is now used offlabel for sleep issues-we have been scripted this as well for sleep but at 50mg noticed no effect and quit taking it. I think imark on this forum takes much more for sleep, 300mg, so our dose was admittedly very low and we may discuss this at the next neuro appt.

We have had several neuros tell us that the hallucinations can be caused by the drugs-both sinemet and mirapex (agonists)-but if you reduce those you lose mobility, a crappy trade off and at some point unacceptable.....and can also be caused by PD itself, in which case reducing sinement/agonists won't help much.

I am sorry to hear your wife is having such a hard time. That is so difficult and no doubt very scary for her.

The equivalent dosage of Trazodone mentioned in the paper posted by me is approx 150 - 200 mg which is scaled up from the mice. Recommend reading the full article and looking at the bar graphs. Also DBM is similar to Curcumin. If I had PD, early on, I would be taking both. Clinical trials take forever and nothing so far comes close to Sinemet.