Effects of pimavanserin: A Synthesis of Findings from 16 Studies

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Original Abstract of the Article

Main Research Findings

Pimavanserin is a medication that has shown potential benefits in treating psychosis associated with Parkinson's disease. 10 , 5 , 15 , 16 , 7 , 12 This medication works by selectively targeting serotonin receptors, specifically the 5-HT2A receptor, acting as an inverse agonist/antagonist. 5 This mechanism distinguishes it from typical antipsychotics, which primarily target dopamine receptors. 11 Research suggests that this selective action may contribute to fewer side effects related to movement and cognition, which are common concerns with traditional antipsychotics. 3 Additionally, pimavanserin has been found to have minimal impact on sleep compared to other antipsychotics.

Benefits and Risks

Benefit Summary

Pimavanserin has demonstrated its potential to alleviate psychosis symptoms, particularly hallucinations and delusions, in individuals with Parkinson's disease. 10 , 5 , 15 , 16 , 7 , 12 Its selective action on serotonin receptors, rather than dopamine receptors, may lead to a reduced risk of movement-related side effects and cognitive impairments compared to conventional antipsychotics. 5 , 11 , 13 Moreover, it has been observed to have a minimal effect on sleep.

Risk Summary

One potential risk associated with pimavanserin is its ability to prolong the QT interval. 1 Furthermore, compared to other antipsychotics, pimavanserin may have a slower onset of action. 14

Comparison Across Studies

Commonalities Among Studies

Multiple studies consistently point to the efficacy of pimavanserin in treating psychosis related to Parkinson's disease. 10 , 5 , 15 , 16 , 7 , 12 A unifying characteristic of pimavanserin across these studies is its selectivity for serotonin receptors, particularly the 5-HT2A receptor. 5 , 11 , 13

Differences Among Studies

While studies generally agree on the potential of pimavanserin, variations exist in the observed effects and side effects. For example, the degree of QT interval prolongation associated with pimavanserin can differ between studies. 1 Similarly, the time frame for the onset of pimavanserin's effects can vary across research findings. 14

Consistency and Discrepancies in Results

While research supports pimavanserin's potential for alleviating psychosis symptoms associated with Parkinson's disease, 10 , 5 , 15 , 16 , 7 , 12 individual responses may vary. It's important to acknowledge the potential for QT interval prolongation, as observed in some studies. 1 These observations highlight the need for careful monitoring and individualized treatment approaches.

Considerations for Real-World Application

Pimavanserin holds promise as a treatment option for psychosis in Parkinson's disease. 10 , 5 , 15 , 16 , 7 , 12 However, potential risks, such as QT interval prolongation, should be taken into account. 1 It's essential to adhere to a doctor's instructions, be aware of potential side effects, and discuss concerns with your healthcare provider.

Limitations of Current Research

Further research is required to gain a more comprehensive understanding of the long-term effects and safety profile of pimavanserin. Large-scale clinical trials with a diverse range of participants are needed to further explore the medication's efficacy and potential variations in individual responses.

Future Research Directions

Research efforts should focus on investigating the long-term effects and safety of pimavanserin. Larger clinical trials, encompassing a broad range of individuals, will be crucial for a more detailed understanding of the medication's effectiveness and potential differences in individual responses.

Conclusion

Pimavanserin offers potential benefits in treating psychosis associated with Parkinson's disease. 10 , 5 , 15 , 16 , 7 , 12 However, it's essential to be aware of potential risks, such as QT interval prolongation, and to adhere to a doctor's instructions for safe and effective use. 1

Literature analysis of 16 papers
Positive Content
15
Neutral Content
1
Negative Content
0
Article Type
1
2
1
1
16
3.

Pimavanserin for Parkinson's Disease psychosis: Effects stratified by baseline cognition and use of cognitive-enhancing medications.

Author: EspayAlberto J, GuskeyMichael T, NortonJames C, CoateBruce, VizcarraJoaquin A, BallardClive, FactorStewart A, FriedmanJoseph H, LangAnthony E, LarsenNiccole J, AnderssonCandace, FredericksDoral, WeintraubDaniel

Effective for cognitive impairment
Enhanced by cognitive enhancers
Cholinesterase inhibitor risk

A study of 185 patients with Parkinson's disease psychosis found that pimavanserin was effective in treating psychosis in patients with cognitive impairment and may be even more effective when used with cognitive-enhancing medications.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Effects of 7-day repeated treatment with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in male rhesus monkeys.

Author: BanksMatthew L

Reduced methamphetamine reinforcement

This study investigated the effects of subchronic treatment with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine reinforcement in monkeys.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

5.

Behavioral effects of clozapine, pimavanserin, and quetiapine in rodent models of Parkinson's disease and Parkinson's disease psychosis: evaluation of therapeutic ratios.

Author: HubbardDavid, HacksellUli, McFarlandKrista

PDP treatment

Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, showed a significantly wider therapeutic window compared to clozapine and quetiapine in an animal model of Parkinson's disease psychosis (PDP). This suggests that pimavanserin may be a more advantageous treatment option for PDP.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

8.

Novel Compounds in the Treatment of Schizophrenia-A Selective Review.

Author: TsapakisEvangelia Maria, DiakakiKalliopi, MiliarasApostolos, FountoulakisKonstantinos N

Schizophrenia treatment
Drug side effects

यो लेखले स्किजोफ्रेनियाको उपचार को लागि नयाँ औषधिहरूको अनुसन्धान को अवस्था को सिंहावलोकन प्रदान गर्छ।

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

9.

Cholinesterase Inhibitors for Delusions and Hallucinations in Alzheimer Disease and Parkinson Disease: Questionably Significant Benefits.

Author: AndradeChittaranjan

Delusions and hallucinations treatment

A meta-analysis of 17 randomized controlled trials found that cholinesterase inhibitor (ChEI) drugs may attenuate delusions and hallucinations in Alzheimer disease (AD) and Parkinson disease (PD). However, the effect sizes were small, and the findings may not significantly change current treatment strategies.

Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

10.

Population Pharmacokinetic Modeling and Stochastic Simulations to Support Pediatric Dose Selection of Pimavanserin.

Author: DarwishMona, Bugarski-KirolaDragana, JaworowiczDavid, OwenJoel, Al QaraghuliFarah, BarryAlida, DeKarskeDaryl

Effective for psychosis
Safe for pediatric use

This analysis used model-based simulations to identify pimavanserin doses for pediatric patients that would generate exposures comparable to adults.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

11.

Design, Synthesis, Molecular Docking, and Biological Evaluation of Novel Pimavanserin-Based Analogues as Potential Serotonin 5-HT<sub>2A</sub> Receptor Inverse Agonists.

Author: AlbujuqNader R, MeanaJ Javier, Diez-AlarciaRebeca, Muneta-ArrateItziar, NaqviArshi, AlthumayriKhalid, AlsehliMosa

5-HT2AR inverse agonist
Neuropsychiatric disorder

This study discovered novel pimavanserin analogues with higher potency as 5-HT2AR inverse agonists. These compounds may represent promising candidates for the treatment of neuropsychiatric disorders.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

Exposure-response Modeling From the CLARITY Trial of Pimavanserin for Adjunctive Treatment of Major Depressive Disorder.

Author: DarwishMona, DirksBryan, PassarellJulie, JaworowiczDavid, BihorelSebastien, HowellBecky, OwenJoel, DeKarskeDaryl, StankovicSrdjan

Major depressive disorder treatment

This study analyzes the exposure-response (E-R) relationships of pimavanserin in patients with major depressive disorder. E-R modeling predicts a relationship between higher pimavanserin exposure and improvement in HAMD-17 score and improvement across multiple secondary efficacy endpoints.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

Comparative Efficacy, Safety, and Acceptability of Pimavanserin and Other Atypical Antipsychotics for Parkinson's Disease Psychosis: Systematic Review and Network Meta-Analysis.

Author: YunusaIsmaeel, RashidNazia, SeyedinRoxanna, ParataneDeepika, RajagopalanKrithika

Improved psychosis
No motor impairment
Cognitive impairment
Quetiapine use

This systematic review and network meta-analysis evaluated the comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) in treating Parkinson's Disease Psychosis (PDP). Pimavanserin and clozapine demonstrated significant improvement in psychosis without affecting motor function. Quetiapine was associated with a significant decline in cognition and should be avoided in patients with PDP and reduced cognitive abilities.

Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Mortality in Patients with Parkinson's Disease-Related Psychosis Treated with Pimavanserin Compared with Other Atypical Antipsychotics: A Cohort Study.

Author: LaytonJ Bradley, FornsJoan, McQuayLisa J, DanyshHeather E, DempseyColleen, AnthonyMary S, TurnerMary Ellen

Reduced mortality

Pimavanserin was associated with lower mortality rates compared to other atypical antipsychotics in patients with Parkinson's disease psychosis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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