Pimavanserin is expected to improve the
effectiveness and
side effect profile of antipsychotics.[8][9][10] The results of a clinical trial examining the efficacy, tolerability and safety of adjunctive pimavanserin to
risperidone and
haloperidol were published in November 2012, and the results showed that pimavanserin potentiated the antipsychotic effects of subtherapeutic doses of
risperidone and improved the tolerability of
haloperidol treatment by reducing the incidence of
extrapyramidal symptoms.[11]
In April 2016, Nuplazid (pimavanserin) was approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.[15][16] The non-binding advisory panel recommendation of 12-to-2 in support of approval that preceded the FDA approval action noted that the drug met an important need, despite its only providing modest benefits and posing serious safety issues.[17]
In June 2018, the FDA approved new dosages of pimavanserin to treat hallucinations and delusions associated with Parkinson's disease psychosis. A 34 mg capsule and 10 mg tablet formulation were approved. Previously, patients were required to take two 17 mg tablets to achieve the recommenced 34 mg dose per day. The 10 mg dose is indicated for patients also taking
CYP3A4 inhibitors (e.g.,
ketoconazole).[18]
HARMONY-Trial
In a phase III, double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov number NTC03325556) pimavanserin was applicated in patients with dementia-related psychosis. The dementia was caused by
Alzheimer's disease, dementia with
Lewy bodies,
frontotemporal dementia,
Parkinson's disease with dementia, or
vascular dementia. The trial was stopped early for efficacy. Patients treated with pimavanserin had a relapse in 13%, without in 28% (hazard ratio 0.35; 95% CI = 0.17–0.73; p = 0.005). Longer and larger trials are suggested.[19]
Controversy
In April 2018,
CNN reported that some in the FDA were concerned that pimavanserin (Nuplazid) was "risky" when it was approved and noted there have been a substantial number of deaths reported by those using the drug. The story further noted that the drug was approved based on a "six-week study of about 200 patients".[20] The FDA began post-market monitoring of the drug to assess the validity of these claims.[21] In September 2018, the FDA stated their review "did not identify any new or unexpected safety findings with Nuplazid, or findings that are inconsistent with the established safety profile currently described in the drug label".[22]
Research
Pimavanserin was studied as a therapeutic agent in
phase 3clinical trials for major depressive disorder and schizophrenia and
phase 2 trials for agitation. It was also under development for the treatment of
insomnia, drug-induced
akathisia, and drug-induced
dyskinesia, but development for these indications was discontinued.[3]
In March 2024 Acadia Pharmaceuticals announced its decision to stop any further clinical trials of pimavanserin after the drug did not improve negative symptoms of schizophrenia better than placebo.[23]
^Gardell LR, Vanover KE, Pounds L, Johnson RW, Barido R, Anderson GT, Veinbergs I, Dyssegaard A, Brunmark P, Tabatabaei A, Davis RE, Brann MR, Hacksell U, Bonhaus DW (August 2007). "ACP-103, a 5-hydroxytryptamine 2A receptor inverse agonist, improves the antipsychotic efficacy and side-effect profile of haloperidol and risperidone in experimental models". The Journal of Pharmacology and Experimental Therapeutics. 322 (2): 862–70.
doi:
10.1124/jpet.107.121715.
PMID17519387.
S2CID28861527.
^"Gov't panel backs drug for Parkinson's". Beaver Dam Daily Citizen. Vol. 105, no. 24. Associated Press. 30 March 2016. p. A8. Retrieved 7 December 2019 – via Newspapers.com.