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Most people associate Parkinson’s with tremors and other motor symptoms. But for some, the disease gives rise to something more terrifying, and much more hidden: psychosis.

As many as half of the million or so Americans with Parkinson’s experience hallucinations, illusions, and delusions — symptoms that are typically benign, but sometimes deeply destructive.

In a cruel twist, these psychiatric disturbances often result from standard Parkinson’s drugs, leaving patients to choose between physical and emotional stability, or try medications that aren’t designed for the condition.


On Tuesday, an advisory panel to the Food and Drug Administration voted 12-2 in favor of approving a new antipsychotic drug — Acadia Pharmaceuticals’ Nuplazid — that’s specifically designed for Parkinson’s psychosis. The agency does not have to follow the panel’s advice, but it usually does. A final regulatory decision will be made by May 1.

The treatment could offer an important new option for those battling the disorder, said Dr. Rachel Dolhun, a spokesperson for the Michael J. Fox Foundation for Parkinson’s Research. “We’re in kind of a quandary here with our current therapies.”


But that hope is tempered by significant uncertainty surrounding the drug’s cost and its effectiveness.

Nuplazid, if given the FDA go-ahead, would undoubtedly cost far more than existing antipsychotics, which are mostly used to treat schizophrenia and are available as generics. In the pivotal trial behind Acadia’s marketing application, Nuplazid showed only modest improvements over placebo, and was tested in a way that makes it difficult to compare against other treatments.

Physicians involved in the trial stand by the drug, nonetheless.

Dr. Jeffrey Cummings, a neurologist at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, said he was struck by some of the patients’ “dramatic” responses.

“Of course, families will also respond to placebos, and that’s why we don’t approve drugs based on anecdotal reports,” said Cummings, who has taken consulting fees from Acadia. “But when families are saying this really made a difference for his life and our lives together, for me it was a pretty impressive study.”

Parkinson’s psychosis usually occurs in the latter stages of the disease, and generally involves nonthreatening visual hallucinations. Cynthia Hatfield, a 72-year-old former banker living in Westerly, R.I., several times a week sees a calico cat resembling one she’d actually owned many years ago, and which her children named “Mushroom.” For years, her hallucinations included a menagerie of small animals.

“Chipmunks and little squirrels and cats, and a little mouse would come out every once in a while,” she said. “I actually enjoy seeing them.”

But even pleasant visions can have disturbing connotations for Parkinson’s patients who aren’t prepared for them.

“If they don’t know and they haven’t been warned, they can get very upset and start to worry” about losing their mind, said Dr. Joseph Friedman, chief of the Butler Hospital Movement Disorders Program, who received consulting fees from Acadia in the past.

The stakes are higher for those who experience frightening hallucinations.

“It’s a little scary sometimes,” said Cheryl Kingston, a Los Angeles writer who has wrestled with Parkinson’s disease for more than 20 years. She recently called 911 because she was convinced that a moose was trying to break through her door to attack her.

“We’re in kind of a quandary here with our current therapies.”

Dr. Rachel Dolhun, Michael J. Fox Foundation

Diane Sagen has been caring for her 77-year-old husband, Jay, since he was first diagnosed with Parkinson’s nine years ago. His hallucinations and delusions have grown worse in recent years, to the point where he often believes she is not his wife. “It just kind of wears you out,” said Sagen, a therapist in Irvine, Calif.

A smaller subset of patients suffers from paranoid delusions, most typically involving the fear that the person’s spouse is cheating on them. Such patients can stubbornly cling to these delusions, and are often too embarrassed to discuss the situation with doctors.

It’s an intractable issue, as the spouse is usually the patient’s primary, or sole, caregiver. Studies have shown that psychosis, more than any other reason, causes Parkinson’s patients to move to nursing homes.

To avoid this fate, doctors will often try to dial down conventional Parkinson’s medications, which work to control tremors and other movement problems by targeting the same neurotransmitters in the brain that can also trigger psychosis. That’s clearly a fraught approach for those with advancing physical symptoms.

The most common alternative: giving antipsychotic medications that are FDA-approved for treating schizophrenia or bipolar disorder, but not Parkinson’s. Doctors believe antipsychotics like Seroquel or Clozaril have some effect on Parkinson’s psychosis, and can help ease anxiety and sleeplessness as well, but clinical studies have failed to show an effect on Parkinson’s psychosis.

Thus the high hopes for Nuplazid (which is also known as pimavanserin), even if those hopes rest on a somewhat shaky foundation, largely composed of a single Phase 3 trial lasting six weeks.

The trial, which was paid for by Acadia, focused on 199 Parkinson’s patients, with half given placebo and the other half Nuplazid. As reported in the Lancet, Nuplazid treatment resulted in a 37 percent improvement on a nine-point clinical scale, compared to a 14 percent bump for those taking placebo.

Is that better than other kinds of antipsychotics? It’s impossible to say, according to Dr. William Ondo, director of movement disorders at the Houston Methodist Neurological Institute, who participated in the study and has sat on Acadia’s scientific advisory board.

Nuplazid failed to demonstrate a benefit in two previous Phase 3 trials. Both included international patients, as well as those from the United States. That skewed the results, Cummings said, because patients in other cultures have differing definitions of hallucinations.

The previous trials also evaluated the drug using the so-called Scale for the Assessment of Positive Symptoms, or SAPS, which is traditionally used to measure the extent of schizophrenia symptoms.

To better gauge the effectiveness in combating Parkinson’s psychosis specifically, Acadia adapted that scale to measure the sorts of hallucinations and delusions experienced by people with the neurodegenerative disease. The modified scale ultimately helped the company show that Nuplazid was better than placebo at controlling symptoms in Parkinson’s patient. But the Parkinson’s version of the scale hasn’t been used when testing other drugs, leading some to question the tool’s clinical validity.

Part of the intrigue surrounding Nuplazid involves its novel molecular approach. Other antipsychotic medications target both the dopamine and serotonin pathways in the brain, and so can interact with drugs that help regulate the movement disorders that burden Parkinson’s patients. Nuplazid, in contrast, targets only the brain’s serotonin receptors — which is perhaps why it was not found to worsen motor symptoms.

“This represents a new pharmacologic paradigm,” Acadia wrote in briefing documents released last week ahead of Tuesday’s advisory committee meeting. (The company declined to comment for this story.)

Significant side effects do exist, however. Totaling across all the Phase 3 trials of Nuplazid, including the two that failed to show a clinical benefit, 8.1 percent of the patients who took the Acadia drug experienced severe side effects, compared to 4.8 percent of those who received placebo. These symptoms included irregular heart rhythms, muscle injury, and weight loss.

In its own briefing documents, the FDA noted that for every two patients who are expected to achieve “much improved” status as a result of Nuplazid, one patient experiences a serious adverse event.

And cost remains a major question for Nuplazid. A price has not been set, but analysts are expecting significant demand for the drug — to the point where some are projecting worldwide sales to top $1 billion or more.

Given the burden of psychosis on Parkinson’s patients and caregivers, it is little surprise that they would eagerly pay for a treatment that might improve their quality of life. Others, for whom the hallucinations are less disturbing, may skip the drug if it comes with a high price tag and even a small chance of side effects.

This story has been updated to include FDA advisory committee’s vote.

  • It is quite pleasant to note that at last some medicine which takes care of the PD patients as treatment has been commercialised. But let us know when the same will be made available to the patients outside USA?

  • Does anybody know if Seroquel and Nuplacid has been prescribed to be taken simultaneouly? A close friend has been taking Seroquel but unfortunately it has not helped with his psychosis. The Dr just prescribed Nuplacid. I was wondering if these two drugs could be taken simultaneously and if so why and or why not. Thank you

    • Yes, you can take seroquel with nuplazid. My mom takes 50 mgs of seroquel and 34 mgs of nuplazid every night. Her hallucinations have stopped. However nuplazid just raised their price to $2200 a month. The pharma industry is evil, and our Dr warned us this would happen. Copay is $110 this month, was only $48 last month. So what do you do? Where do you draw the line with the thieves, who are selling addictive drugs to our loved ones?

  • My husband started on nuplazid three days ago. I know it is supposed to take a couple weeks to kick in. He is also on an antibiotic, vycomyicin. While he has been depressed due to a recent location move, he is emotionally flat, and refuses to do much of anything or talk. Would this be due to the new drug? He had lots of hallucinations prior to the new drug, which is why he is trying it.

  • I decided to share this to help someone out there who is still held with Parkinson’s.
    My dad suffered from parkinson’s for 18 years and we traveled round the world from one hospital to another neurologist and spent thousands of dollars and even got scammed in this process of seeking a cure and the problem still persisted. He acted weird and aggressive and this was so scary. All thanks to Health Herbal Clinic who was able to use there herbal medicine to cure him permanently. He is one of the Honest men out there. If you want to contact them on how to get this herbal medicine or for info just reach them directly on healthherbalclinic(at)gmail(dot)com or website on www(dot)healthherbalclinic(dot)weebly(dot)com Thanks admin.

    • If this Herbal Drug is so good why doesn’t the FDA approve it or main stream Parkinson Groups like The Parkinsons Foundation recommend it? It’s like it’s a big secret. It doesn’t make sense that if the Health Herbal Clinic has a helpful remedy for Parkinson’s Disease that it isn’t front page news…..I think you are just trying to make money by preying on the desperate who are vulnerable. SHAME ON YOU.

  • My mom has had parkinsons for about 5 yrs, my dad died 2 yrs ago so I am her caregiver, her neurologist upped her carbo and started her on amantadine, she had horrifying hallucinations that the fiest event she urn her feet in scalding water to thinking someone had locked her in a closet, I took her off all meds and she got better slowly got her on her meds again and she off and on sees people in her house and animals and also sees my dad that passed. we started her on nuplazid and its been about 5 weeks and all shadows, people and animals are gone so far sje sleeps better and stays more awake during the day. It took like 3 weeks to see any improvement. Hope it is really helping and hopes this helps anyone else that loved ones have this horrible issues.

  • This medicine has changed my mother’s life. She started having bad hallucinations that ended her up in the hospital. Her neurologist put her on this drug and it worked great. We have our mom back and happy. Thank you do much!

  • Hello……………
    I’m Monica Henry by name, I’m here to share my testimony about Dr Mapipa herbal medicine Cure , he has the cure to different kinds of diseases, he cured me and my husband of COPD and Parkinson’s disease,me and my husband was diagnosed of COPD and Parkinson’s 2013,we live in pain for years ,so desperate for cure. one day i was glancing through different website I saw different testimonies about dr mapipa,so many people saying he cured them of different diseases,i was so surprised and skeptical,but i have so option because me and my husband need the cure desperately ,so i contacted him via his email.drmapipaherbalmedicinehome(at)gmail(dot)com,he replied and Needed some Information about me and my husband, then I sent them to him,then he sent me the herbal medicine through FEDEX Courier Service,The courier service called me after 2days that i must be at home because they will be delivering that day ,which i did ,when i received the herbal medicine ,we call dr mapipa then he told us how to use the herbal medicine ,he said we will be totally cured after 30days of usage which we believed with after 30days of usage they was a lot of changes in our life’s ,so we went for check-up, I was tested COPD FREE and my husband was fully recovered from Parkinson’s,it was like a miracle to my family ,please viewer my testimony is real ,any negative news you see online or hear about DR MAPIPA is false ,he is the only real herbal doctor online ,so many fake herbal doctor are trying to spoil his name,please viewer don’t mind them ,DR MAPIPA will never let you down ,he is a great man.

    • If this Herbal Drug is so good why doesn’t the FDA approve it or main stream Parkinson Groups like The Parkinsons Foundation recommend it? It’s like it’s a big secret. It doesn’t make sense that if Dr. Mapipa has a helpful remedy for Parkinson’s Disease that it isn’t front page news…..I think you are just trying to make money by preying on the desperate who are vulnerable. SHAME ON YOU.

  • My mother is on Nuplazid and has experienced a tremendous improvement in her quality of life. She had both “friendly” and frightening hallucinations and her delusions about my father having an affair and the bad intentions of the aides in her assisted living facility left her fearful, confused and agitated. She was put on Seroquel initially and that didn’t work but it did sedate her. Now on Nuplazid she sleeps very well, wakes rested, isn’t sedated, isn’t fearful, doesn’t have delusions or hallucinations and is significantly more happy and peaceful. She is also much more present and her cognitive ability has improved (probably because she isn’t distracted by her hallucinations, delusions and fears). We couldn’t be more thrilled with the results.

  • my husband just tried nuplazid and had a very negative experience. It did not stop his hallucinations and it made him very agitated and anxious. He was much more confused also. It was not a good fit for him at all. We stopped it after only one week because it had such a negative effect on his behavior. We were disappointed that this was not the answer we were hoping for.

    • Linda, when I spoke to the specialist pharmastrist and my husband psychiatrist told me that it takes between 7-12 days , and that husband would become worst during that time . 75% PD patient it works but 25% it doesn’t, my husband was in his forties when he diagnose with PD (1998) and 2012 dementia. He was place in a geriatric psych unit last July, worst he’s ever been. I’m praying this drug helps him. He started Nuplazid Sunday 28 Aug he was good Monday , Tuesday, Wednesday , Thursday some halluations but Thursday night and Friday had to give him Zyprexa . He was taking seroquel but doctor said he has to be off that to start nuplazid. I know how hard this is, I gave caregivers with him while I work, they are doing a great job and are very supported. I wish you the best …

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