Pimavanserin

BACKGROUND Many patients with dementia with Lewy bodies (DLB) experience cholinesterase inhibitor- and antipsychotic-resistant psychosis. The new second-generation antipsychotic pimavanserin has been used with some success in the treatment of psychosis in other forms of dementia, including Alzheimer disease and Parkinson disease dementia. It is possible that pimavanserin may also be useful in the treatment of psychosis in DLB. We sought to describe the disease course and treatment of psychosis in 4 patients with DLB who were prescribed pimavanserin after other medications failed to reduce the frequency or severity of hallucinations and delusions...

BACKGROUND: Pimavanserin, a serotonin 5HT-2A receptor inverse agonist is the first-line, FDA-approved treatment of hallucinations and delusions associated with Parkinson's Disease psychosis (PDP), which occurs in up to 50% of PD patients. The neurobiological mechanism underlying the therapeutic effectiveness of Pimavanserin in PDP remains unknown. Several earlier studies have shown that treatment with 5HT-2A antagonists and other drugs acting on the serotonergic system such as SSRIs increase Brain derived neurotrophic factor (BDNF) levels in rodents...

Alzheimer's disease (AD) ranks first among the causes of dementia worldwide. AD can develop a psychotic manifest at a significant rate. AD prognosis worsens by added psychosis clinic. There is no treatment approved by the United States Food and Drug Administration (FDA) among antipsychotics for Alzheimer's disease Psychosis (ADP). However, pimavanserine, an atypical antipsychotic, has been approved by the FDA for Parkinson's psychosis. It is predicted that pimavanserin, a new antipsychotic, will fill an important gap in this area...

Schizophrenia is a chronic neuropsychiatric syndrome that significantly impacts daily function and quality of life. All of the available guidelines suggest a combined treatment approach with pharmacologic agents and psychological interventions. However, one in three patients is a non-responder, the effect on negative and cognitive symptoms is limited, and many drug-related adverse effects complicate clinical management. As a result, discovering novel drugs for schizophrenia presents a significant challenge for psychopharmacology...

PURPOSE OF REVIEW: Lewy body dementia (LBD) encompasses dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). This article will emphasize potential disease-modifying therapies as well as investigative symptomatic treatments for non-motor symptoms including cognitive impairment and psychosis that can present a tremendous burden to patients with LBD and their caregivers. RECENT FINDINGS: We review 11 prospective disease-modifying therapies (DMT) including four with phase 2 data (neflamapimod, nilotinib, bosutinib, and E2027); four with some limited data in symptomatic populations including phase 1, open-label, registry, or cohort data (vodabatinib, ambroxol, clenbuterol, and terazosin); and three with phase 1 data in healthy populations (Anle138b, fosgonimeton, and CT1812)...

Delusions and hallucinations are common in Alzheimer disease (AD) and Parkinson disease (PD), especially in the later stages of illness. Antipsychotic drugs are effective in treating these psychotic symptoms but are associated with an increased risk of serious adverse events, including mortality. There is therefore a need to explore other treatment approaches. In this context, a recent individual patient data meta-analysis of 17 randomized controlled trials (RCTs) conducted in AD (12 RCTs) and PD (5 RCTs) found that the cholinesterase inhibitor (ChEI) drugs donepezil, rivastigmine, and galantamine attenuated the severity of both delusions and hallucinations in both AD and PD...

Pimavanserin is a selective serotonin-modulating agent with inverse agonist/antagonist activity at the 5-HT2A receptor. Safety and efficacy of pimavanserin 34 mg once daily was studied in adults with hallucinations and delusions associated with Parkinson's disease psychosis and other neuropsychiatric conditions. This analysis used model-based simulations of pimavanserin steady-state exposures to identify a dose that generated pediatric exposures comparable with adult exposures achieved with 34 mg pimavanserin...

Mood disorders are recurrent/chronic diseases with variable clinical remission rates. Available antidepressants are not effective in all patients and often show a relevant response latency, with a range of adverse events, including weight gain and sexual dysfunction. Novel rapid agents were developed with the aim of overcoming at least in part these issues. Novel drugs target glutamate, gamma-aminobutyric acid, orexin, and other receptors, providing a broader range of pharmacodynamic mechanisms, that is, expected to increase the possibility of personalizing treatments on the individual clinical profile...

There is concern for important adverse effects with use of second-generation antipsychotics in Parkinson's disease psychosis (PDP) and dementia-related psychosis. Pimavanserin is the only antipsychotic drug authorized for PDP and represents an inverse agonist of 5-HT2A receptors (5-HT2AR) lacking affinity for dopamine receptors. Therefore, the development of serotonin 5-HT2AR inverse agonists without dopaminergic activity represents a challenge for different neuropsychiatric disorders. Using ligand-based drug design, we discovered a novel structure of pimavanserin analogues ( 2 , 3 , and 4 )...

Parkinson's disease (PD) is the second-most common neurodegenerative disorder with a long-term 60% cumulative prevalence of PD psychosis. Medical treatment is limited to few atypical antipsychotic drugs with low affinity to dopamine D2 receptors. In 2016, pimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved by the US Food and Drug Administration (FDA) as the only treatment for PD psychosis (PDP). This article provides an overview of the epidemiology, pathophysiology, and treatment options for PDP and illuminates the mode of action and therapy options with pimavanserin and the current study data...

BACKGROUND: Pimavanserin (PIM) is the only FDA approved atypical antipsychotic (AAP) for the treatment of Parkinson's Disease Psychosis (PDP) while other off-label AAPs like quetiapine (QUE) are also used. Real-world comparative effects of PIM and QUE on health resource utilization (HCRU) may provide insights about their relative benefits. OBJECTIVES: To examine annual HCRU among newly initiated PIM or QUE monotherapy among patients with PDP. METHODS: Retrospective analysis of 100% Medicare (Parts A, B, and D) claims of patients with PDP during 1 January 2013 to 31 December 2019 was conducted...

In recent years, it is common for a single drug to be developed for multiple diseases almost simultaneously, e.g., pimavanserin and psilocybin. Although there was gloomy news for the field of neuropsychopharmacology, such as withdrawal of the world's leading mega-pharmaceutical companies from the development of CNS drugs, drugs based on novel mechanisms of action have been investigated. This is a new dawn in the field of clinical psychopharmacology.

BACKGROUND: Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors are located postsynaptically to serotonergic neurons in the frontal cortex and mediate both excitatory and inhibitory neurotransmissions. However, the effectiveness and tolerance of negative modulators of 5-HT2A receptors in Alzheimer's disease psychosis (ADP) are uncertain. OBJECTIVES: To detect the negative modulators of the 5-HT2A receptor as a cure for ADP...

INTRODUCTION: Dementia with Lewy bodies (DLB) is characterized by neurocognitive disorders associated with core clinical features including hallucinations. There is currently no cure but a combination of symptomatic treatments: clozapine is commonly used in DLB-related psychosis. Pimavanserin is a serotonin 5HT-2A receptor inverse agonist that has recently been shown to reduce psychosis related to dementia. Trazodone is a serotonin reuptake inhibitor and a 5-HT2 receptor antagonist: it is effective in the treatment of the frontal syndrome and is commonly used in frontotemporal degeneration...

LPM6690061 is a novel compound with 5-HT2A receptor antagonist and inverse agonist activities. To support the clinical trial and marketing application of LPM6690061, a series of pharmacology and toxicology studies have been conducted. In vitro and in vivo pharmacology studies showed that LPM6690061 had high inverse agonism and antagonism activities against human 5-HT2A receptors, and demonstrated significant antipsychotic-like effects in two rat models: the DOI-induced head-twitch model and the MK-801-induced hyperactivity model, which was more effective than the control drug pimavanserin...

BACKGROUND: Pimavanserin is currently the only antipsychotic approved for Parkinson's disease (PD) psychosis, yet its relative safety compared with treatment alternatives has not been thoroughly assessed. OBJECTIVES: This study aimed to compare hospitalization and mortality risk in Medicare beneficiaries with PD receiving new prescriptions of pimavanserin or quetiapine for PD psychosis. METHODS: The study identified new users of pimavanserin and quetiapine from a 15% national sample of Medicare fee-for-service claims collected between May 1, 2016, and December 30, 2018...

Exploring the possible correlations between gene variations and the clinical effects of the new-generation antipsychotics is considered essential in the framework of personalized medicine. It is expected that pharmacogenetic data will be useful for increasing the treatment efficacy, tolerability, therapeutic adherence, functional recovery, and quality of life in patients with severe psychiatric disorders (SPD). This scoping review investigated the available evidence about the pharmacokinetics, pharmacodynamics, and pharmacogenetics of five new-generation antipsychotics, i...

This study aimed to examine differential prescribing due to channeling and propensity score non-overlap over time in new versus established treatments for common neurological conditions. We conducted cross-sectional analyses on a national sample of US commercially insured adults using 2005-2019 data. We compared new users of recently approved versus established medications for management of diabetic peripheral neuropathy (pregabalin versus gabapentin), Parkinson disease psychosis (pimavanserin versus quetiapine), and epilepsy (brivaracetam versus levetiracetam)...

BACKGROUND: Alzheimer's disease (AD) is characterized by neuropsychiatric symptoms (NPS), which cause great misery to those with dementia and those who care for them and may lead to early institutionalization. OBJECTIVE: The present systematic review aims to discuss the various aspects of Alzheimer's, including treatment options. METHODS: The databases Embase, PubMed, and Web of Science were searched to collect data. RESULT: Incipient cognitive deterioration is commonly accompanied by these early warning signals of neurocognitive diseases...

BACKGROUND: The current comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) in treating Parkinson's Disease Psychosis (PDP) are not entirely understood. OBJECTIVE: To evaluate comparative efficacy, safety, and acceptability of AAPs in patients with PDP. METHODS: We conducted a systematic review and a network meta-analysis to compare the efficacy, safety, and acceptability of pimavanserin, quetiapine, olanzapine, clozapine, ziprasidone, and risperidone...