Trial of Pimavanserin in Dementia-Related Psychosis
In RCT (n=351) of this selective 5-HT2A inverse agonist that was stopped early for efficacy, patients who had response to treatment (n=217) had lower risk of relapse with continuation of drug than with discontinuation (13% vs. 28%, placebo; HR 0.35; 95% CI, 0.17 to 0.73; p=0.005)
Source:
New England Journal of Medicine
SPS commentary:
The HARMONY trial was initiated as a phase 3, randomised discontinuation trial of the safety and efficacy of pimavanserin for the treatment of delusions and hallucinations associated with several common forms of dementia. This design addresses the question of whether treatment with pimavanserin would confer sustained benefits with respect to psychosis in patients with an initial response to the drug; the design also translates to decisions about medication discontinuation and minimizes exposure to ineffective therapy.
According to an editorial, generating and using evidence from studies involving a mix of patients with different dementia subtypes subsumed under the “dementia” umbrella diagnosis seems to have become an accepted practice in the treatment of behavioural and psychotic symptoms associated with all forms of dementia. It notes the paucity of data on the efficacy of antipsychotics in dementia subtypes with the exception of Alzheimer’s disease, for which sufficient evidence has accumulated to support the practice of using antipsychotics to control psychosis. It discusses whether pimavanserin should be held to the same standard, whether the standard should be reevaluated and future studies of these treatments be limited to individual dementia subtypes.
In April, the FDA rejected pimavanserin for hallucinations and delusions associated with dementia-related psychosis because of a lack of statistical significance in some of the dementia subgroups in this RCT.