From the Journals

Atypical used in Parkinson’s lifts hallucinations, delusions in refractory schizophrenia



Pimavanserin (Nuplazid), an atypical antipsychotic approved to treat hallucinations and delusions in Parkinson’s disease, shows promise as a treatment for patients with refractory schizophrenia who fail to respond to clozapine, a retrospective study suggests.

“Within a month, sometimes 2 months, hallucinations and delusions that have persisted for years were completely gone,” said lead author Henry A. Nasrallah, MD, in an interview. The study was published in Schizophrenia Research.

Dr. Nasrallah and his colleagues launched the study in a bid to help “the most desperate group of patients” with schizophrenia – the 60% of those with refractory psychosis who do not respond to clozapine.

“This group of patients is so desperate that psychiatrists have used everything in our pharmacopeia,” said Dr. Nasrallah, the Sydney W. Souers Endowed Chair and professor and chairman of the department of psychiatry and behavioral neuroscience at Saint Louis University. “Nothing has been shown to work. We decided to give them this medication [pimavanserin], which was approved by the FDA [Food and Drug Administration] 2 years ago for hallucinations and delusions for Parkinson’s disease.”

For the new study, Dr. Nasrallah and his coauthors gave 34 mg/day of pimavanserin to 10 patients, aged 21-77 years, with schizophrenia or schizoaffective disorder and refractory hallucinations and delusions. The subjects, all of whom live in a residential group home, had either failed clozapine (n = 6) or failed several antipsychotics but had not yet received clozapine (n = 4).

The results, Dr. Nasrallah said, were remarkable. “Not only did they get relief from their delusions and hallucinations, but nursing staff reported they were much more sociable and affable, getting out of their rooms, and mixing and mingling. It seems to help them beyond suppressing delusions and hallucinations. It made them more sociable and pleasant.”

Patients were able to avoid blood tests and the “sometimes life-threatening side effects of clozapine,” he said. According to the study, no patients needed to discontinue treatment because of safety or tolerability.

However, pimavanserin is expensive. According to, monthly prices for 60 tablets of 17 mg pimavanserin – equal to the daily dose in this study – run from $2,759 to $2,907 with a free coupon.

Should psychiatrists prescribe the drug now for treatment-resistant schizophrenia? “We use drugs off label all the time for patients who do not have any FDA-approved medication,” Dr. Nasrallah said. “Sometimes, off-label use in psychiatry is a necessity, because around 80% of DSM-5 disorders do not have any approved drugs at this time.”

Moving forward, “double-blind, placebo-controlled trials of pimavanserin in refractory schizophrenia are certainly warranted, given these findings,” Dr. Nasrallah and his coauthors wrote. “It would also be interesting to test pimavanserin in first-episode psychosis to identify a ‘serotonergic subtype’ of the schizophrenia syndrome but also to completely avoid the extrapyramidal side effects of dopamine antagonists, to which first-episode psychosis patients are especially susceptible.”

No outside funding was reported. Dr. Nasrallah reported advisory board and consultant and speaker’s bureau relationships with Acadia, Alkermes, Allergan, Janssen, Lundbeck, Neurocrine Biosciences, Otsuka Pharmaceutical, Sunovion, and Teva. Another author reported no disclosures, and a third author reported numerous disclosures.

SOURCE: Nasrallah HA et al. Schizophr Res. 2019 Mar 2. doi: 10/1016/j.schres.2019.02.018.

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