Trial of Pimavanserin in Dementia-Related Psychosis
| Autor: | Pierre N. Tariot, Maria E. Soto-Martin, Srdjan Stankovic, Clive Ballard, Erin P. Foff, Bradley W. McEvoy, Davangere P. Devanand, Jeffrey L. Cummings, Daniel Weintraub, David L. Sultzer, Deniz E. Erten-Lyons, James M. Youakim |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Psychosis medicine.medical_specialty Hallucinations MEDLINE Pimavanserin Kaplan-Meier Estimate law.invention chemistry.chemical_compound Randomized controlled trial Double-Blind Method Piperidines law Recurrence Internal medicine mental disorders medicine Inverse agonist Dementia Humans Urea Aged Proportional Hazards Models Aged 80 and over Proportional hazards model business.industry food and beverages Parkinson Disease General Medicine Middle Aged medicine.disease Clinical trial chemistry Psychotic Disorders Female business Antipsychotic Agents |
| Zdroj: | The New England journal of medicine. 385(4) |
| ISSN: | 1533-4406 |
| Popis: | Patients with dementia due to neurodegenerative disease can have dementia-related psychosis. The effects of the oral 5-HTWe conducted a phase 3, double-blind, randomized, placebo-controlled discontinuation trial involving patients with psychosis related to Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, frontotemporal dementia, or vascular dementia. Patients received open-label pimavanserin for 12 weeks. Those who had a reduction from baseline of at least 30% in the score on the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions (SAPS-H+D, with higher scores indicating greater psychosis) and a Clinical Global Impression-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved) at weeks 8 and 12 were randomly assigned in a 1:1 ratio to continue receiving pimavanserin or to receive placebo for up to 26 weeks. The primary end point, assessed in a time-to-event analysis, was a relapse of psychosis as defined by any of the following: an increase of at least 30% in the SAPS-H+D score and a CGI-I score of 6 (much worse) or 7 (very much worse), hospitalization for dementia-related psychosis, stopping of the trial regimen or withdrawal from the trial for lack of efficacy, or use of antipsychotic agents for dementia-related psychosis.Of the 392 patients in the open-label phase, 41 were withdrawn for administrative reasons because the trial was stopped for efficacy; of the remaining 351 patients, 217 (61.8%) had a sustained response, of whom 105 were assigned to receive pimavanserin and 112 to receive placebo. A relapse occurred in 12 of 95 patients (13%) in the pimavanserin group and in 28 of 99 (28%) in the placebo group (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.73; P = 0.005). During the double-blind phase, adverse events occurred in 43 of 105 patients (41.0%) in the pimavanserin group and in 41 of 112 (36.6%) in the placebo group. Headache, constipation, urinary tract infection, and asymptomatic QT prolongation occurred with pimavanserin.In a trial that was stopped early for efficacy, patients with dementia-related psychosis who had a response to pimavanserin had a lower risk of relapse with continuation of the drug than with discontinuation. Longer and larger trials are required to determine the effects of pimavanserin in dementia-related psychosis. (Funded by Acadia Pharmaceuticals; HARMONY ClinicalTrials.gov number, NCT03325556.). |
| Databáze: | OpenAIRE |
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