Evaluation of the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer's disease psychosis: a phase 2, randomised, placebo-controlled, double-blind study

Ballard, Clive; Banister, Carol; Khan, Zunera; Cummings, Jeffrey L.; Demos, George; Coate, Bruce; Youakim, James M.; Owen, Randall; Stankovic, Srdjan; Tomkinson, E; McDermid, Joanne; Ocal, Delik; Testad, Ingelin; Qayyum, Mustabshira; Kemos, Polychronis; Borejko, Olga; Megalogeni, Maria; Brookes, Ella; Petrava, Anya; Silva, Miguel Da; Nunez, Kayleigh-Marie

doi:10.1016/s1474-4422(18)30039-5

Cited by 159 publications

(153 citation statements)

References 36 publications

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“…Patients with dementia (Mini-Mental State Examination (MMSE) score <20) were excluded in the pivotal clinical trial (30); but some patients exhibited a limited degree of cognitive impairment. A post hoc subgroup analysis conducted from the Phase 3 study, evaluated randomized patients according to the presence or absence of cognitive impairment, defined as a MMSE score of 21 to 24 for cognitive impairment versus ≥25 for non-impaired (46).…”

Section: Subgroup Analysis Of Outcome By Baseline Mmsementioning

confidence: 99%

“…A completed study suggests that pimavanserin is effective in reducing hallucinations and delusions in patients with ADP (30). …”

Section: A Phase 2 Study Of Pimavanserin For Alzheimer’s Disease Psycmentioning

confidence: 99%

“…This was a Phase 2, 12-week, randomized, double-blind, placebo-controlled, single-center study to assess the safety and efficacy of pimavanserin 34 mg once daily in nursing home residents with ADP (30). The pre-specified primary and secondary endpoints were evaluated at Week 6 of treatment.…”

Section: A Phase 2 Study Of Pimavanserin For Alzheimer’s Disease Psycmentioning

confidence: 99%

“…In the analytic plan of the ADP Phase 2 study data, a pre-specified subgroup analysis was conducted in patients who had more severe psychotic symptoms (hallucinations and delusions) at baseline as measured by NPI-NH psychosis score (30, 47). This pre-specified analysis corroborated the primary endpoint results and showed that patients with more severe psychotic symptoms at baseline (NPI-NH psychosis score ≥12) experienced greater improvement compared to patients with less severe symptoms at baseline (NPI-NH psychosis score <12) (Figure 2).…”

Section: Subgroup Analysis Of Patients With More Severe Psychosis At mentioning

confidence: 99%

“…Recently, pimavanserin was shown to improve hallucinations and delusions in patients with AD psychosis (ADP) (30). Analyses from this study also demonstrated that pimavanserin did not negatively impact cognitive function in these patients (Table 2).…”

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Pimavanserin: Potential Treatment for Dementia-Related Psychosis

et al. 2018

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Psychosis is common across dementia types with a prevalence of 20% to 70%. Currently, no pharmacologic treatment is approved for dementia-related psychosis. Atypical antipsychotics are frequently used to treat these disorders, despite significant safety concerns. Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved in the U.S. for treating hallucinations and delusions associated with Parkinson’s disease psychosis (PDP). Patients in the pimavanserin group experienced a significant (p=0.001) improvement in Scale for the Assessment of Positive Symptoms – Parkinson’s disease (SAPS-PD) scores vs. placebo. In a subgroup analysis of patients with cognitive impairment (MMSE score ≥21 but ≤24), the observed improvement on the SAPS-PD with pimavanserin (N=50) was also significant (p=0.002) and larger than in the overall study population without an adverse effect on cognition. In a Phase 2 study with pimavanserin in Alzheimer’s disease psychosis, pimavanserin significantly (p=0.045) improved psychosis at Week 6 vs. placebo on the NPI-NH Psychosis Score (PS). In a prespecified subgroup of patients with a baseline NPI-NH PS ≥12, a substantively larger treatment effect (p=0.011) was observed vs. participants with NPI-NH PS

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Section: Subgroup Analysis Of Outcome By Baseline Mmsementioning

confidence: 99%

“…A completed study suggests that pimavanserin is effective in reducing hallucinations and delusions in patients with ADP (30). …”

Section: A Phase 2 Study Of Pimavanserin For Alzheimer’s Disease Psycmentioning

confidence: 99%

Section: A Phase 2 Study Of Pimavanserin For Alzheimer’s Disease Psycmentioning

confidence: 99%

Section: Subgroup Analysis Of Patients With More Severe Psychosis At mentioning

confidence: 99%

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Pimavanserin: Potential Treatment for Dementia-Related Psychosis

et al. 2018

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Progress in Pharmacologic Management of Neuropsychiatric Syndromes in Neurodegenerative Disorders

Cummings,

Lanctot,

Grossberg

et al. 2024

JAMA Neurol

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ImportanceNeuropsychiatric syndromes (NPSs) are common in neurodegenerative disorders (NDDs); compromise the quality of life of patients and their care partners; and are associated with faster disease progression, earlier need for nursing home care, and poorer quality of life. Advances in translational pharmacology, clinical trial design and conduct, and understanding of the pathobiology of NDDs are bringing new therapies to clinical care.ObservationsConsensus definitions have evolved for psychosis, agitation, apathy, depression, and disinhibition in NDDs. Psychosocial interventions may reduce mild behavioral symptoms in patients with NDD, and pharmacotherapy is available for NPSs in NDDs. Brexpiprazole is approved for treatment of agitation associated with Alzheimer disease dementia, and pimavanserin is approved for treatment of delusions and hallucinations associated with psychosis of Parkinson disease. Trials are being conducted across several of the NDDs, and a variety of mechanisms of action are being assessed for their effect on NPSs.Conclusions and RelevanceDetection and characterization of NPSs in patients with NDDs is the foundation for excellent care. New definitions for NPSs in NDDs may inform choices regarding clinical trial populations and translate into clinical practice. Psychosocial and pharmacologic therapies may reduce behavioral symptoms and improve quality of life for patients and caregivers. Approved agents may establish regulatory precedents, demonstrate successful trial strategies, and provide the foundation for further advances in treatment development.

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