Nuplazid (pimavanserin) / Acadia Pharma - LARVOL DELTA

Safety and efficacy of pimavanserin in patients with Lewy body dementia experiencing dementia-related psychosis in the HARMONY study. (PubMed, BMC Neurol) - P3 | "Psychosis relapse risk was significantly lower with pimavanserin vs. placebo in patients with Lewy body dementia. Pimavanserin was also well tolerated and did not worsen motor or cognitive function. Results should be interpreted cautiously since this study is a post hoc analysis of a previous trial that was not originally designed or powered to draw clinical conclusions based on dementia subgroups."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease • Psychiatry

Pimavanserin attenuates precipitated morphine withdrawal syndrome and its aversiveness in rats. (Neuroscience 2025) - "Compared with the morphine-infused/saline-injected rats, pimavanserin again reduced the increase in withdrawal signs, this time by 75.6%, p < .001. The results suggest that pimavanserin might alleviate some symptoms associated with morphine physical dependence."

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Adsorptive removal of pimavanserin from water using β-cyclodextrin polymer coated PVDF nanofibers. (PubMed, Sci Rep) - "The versatility of this polymer allows it to be polymerized onto various substrates, making it a promising candidate for large-scale applications. The results suggest that this innovative adsorptive nanofiber system could play a crucial role in combating water pollution globally, offering an effective and scalable solution for the removal of hazardous pharmaceuticals from wastewater."

Journal

Real-world evidence of pimavanserin utilization among patients with Parkinson's disease psychosis: a review of real-world data that augments data from randomized controlled trials. (PubMed, J Comp Eff Res) - "In addition to demonstrating symptom improvements in clinical trials, PIM appears to consistently show favorable outcomes among published real-world evidence (RWE) studies compared with off-label AAPs (e.g., quetiapine [QUE]). Additionally, PIM was associated with higher treatment compliance, fewer falls or fractures and lower overall mortality risk versus other-AAPs or QUE. PIM's favorable real-world profile versus other-AAPs or QUE across community and NH/LTC settings complement the favorable clinical trial findings."

HEOR • Journal • Real-world evidence • Review • CNS Disorders • Movement Disorders • Musculoskeletal Diseases • Orthopedics • Parkinson's Disease • Psychiatry

7814: From Collapse to Control: Rewriting OSA Treatment With Targeted Pharmacotherapy – Respiratory-Related Sleep Disorders Section (CHEST 2025) - "This session will explore the latest clinical data and mechanistic rationale behind a diverse group of agents, including tirzepatide (weight loss/passive critical closing pressure), atomoxetine-oxybutynin (dilator muscle tone), pimavanserin and buspirone (arousal threshold), and acetazolamide (loop gain). Attendees will learn how to think beyond CPAP and match the right therapy to the right OSA phenotype."

CNS Disorders • Cognitive Disorders • Obstructive Sleep Apnea • Sleep Disorder

Glutamate modulation by evenamide produces statistically significant and clinically relevant improvement in patients with treatment-resistant schizophrenia (ECNP 2025) - "Recent examples include pimavanserin, which did not provide evidence of significant benefit as adjunctive therapy in inadequate responders [1] and Lu-AF35700 which failed to produce significant improvement as monotherapy in TRS [2]. Glycine re-uptake inhibition with bitopertin did not produce significant benefits in patients with inadequately controlled positive symptoms [3]. New results with KarXT indicate no significant benefit compared to placebo when used as add-on to second-generation antipsychotics (SGA) in inadequate responders despite having demonstrated improvement in acutely psychotic patients as monotherapy [4]...Results from the more recent, phase 3, double-blind, placebo-controlled, 4-week, add-on study demonstrated statistically significant and clinically important improvements in 291 patients with inadequate response to SGA including clozapine. Positive findings from these two studies, which will need to be confirmed in a larger phase 3 trial in patients..."

Clinical • CNS Disorders • Epilepsy • Psychiatry • Schizophrenia

Design of the Phase 2, Double-Blind, Placebo-Controlled, Multicenter Study Investigating the Efficacy and Safety of ACP-204, a Novel 5-HT2A Inverse Agonist, in Adults With Lewy Body Dementia Psychosis (MDS Congress 2025) - "ACP-204 is a selective 5-HT2A (less so at 5-HT2C) inverse agonist/antagonist discovered to have an improved pharmacological profile compared with pimavanserin, which is approved for PDP. This will be the first clinical study to evaluate the efficacy and safety of ACP-204 in patients with LBDP, a population with considerable unmet needs. Abstract Figure"

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease • Psychiatry

Duration of Illness and Response to Pimavanserin in Parkinson's Disease Psychosis: Post-Hoc Analysis of Clinical Trial Data (MDS Congress 2025) - "Our analysis found that, at all levels of response, a greater percentage of patients with PDP responded to pimavanserin when treated <6 months after initial psychotic symptoms compared with patients treated ≥6 months after initial psychotic symptoms (CR, 30.8% vs 11.0%); findings were consistent for durations of <12 vs ≥12 months since initial symptoms. Table 1 Table 2"

Clinical • Retrospective data • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Therapeutic potential of saffron for negative and cognitive symptoms in schizophrenia: clinical and preclinical insights (ECNP 2025) - "While recent agents (i.e., cariprazine, muscarinic receptor agonists, glutamate modulators, and pimavanserin) have shown partial promise, consistent benefits for negative and cognitive domains remain elusive...Results One randomized controlled trial (RCT) (2) evaluated adjunctive saffron (15 mg every 12 hours for 8 weeks) in 26 patients with chronic schizophrenia receiving risperidone, compared to 24 patients receiving risperidone and placebo...Three preclinical studies used rodent models of schizophrenia-like symptoms induced by MK-801 (a non-competitive NMDA receptor antagonist) (3), ketamine (4), or apomorphine-induced (5) models...Although the precise mode of action in humans remains to be fully elucidated, saffron's favorable tolerability profile and potential benefits on metabolic dysfunction support further investigation into its role in alleviating negative symptoms of schizophrenia. Larger, well-controlled trials are warranted to replicate these findings,..."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia • SIRT1

Visual Hallucinations in Serotonergic Psychedelics and Lewy Body Diseases. (PubMed, Schizophr Bull) - "Examining cortical and neuromodulatory similarities between LBD- and SP-induced VH may elucidate the link between sensory degradation, excitation, and hallucinogenesis. Future research should employ real-time neuroimaging of discrete hallucinatory episodes to identify shared mechanisms and develop targeted interventions for LBD hallucinations."

Journal • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Movement Disorders • Retinal Disorders

Quantification of psychedelic occupancy using [11C]Cimbi-36 PET: methodological considerations (ECNP 2025) - "PET studies using [11C]Cimbi-36 to evaluate the occupancy of the 5-HT2AR by psilocybin in human [2] and by pimavanserin in the non-human primate (NHP) [3] have found maximal occupancy levels significantly < 100%... We have evaluated the data from [11C]Cimbi-36 PET studies in humans done before and after blockade of the cerebral 5-HT2AR by risperidone (N=5) and ketanserin (N=5) [4]... Our results are consistent with the notion that the findings of maximal occupancy if the 5-HT2AR of <100% are due to the underestimation of the true VND due to the use of the cerebellum as a reference region, and the use of the correct non-displaceable binding levels will demonstrate maximal occupancy indistinguishable from 100%. Future occupancy studies using [11C]Cimbi-36 PET should consider the potential effects of such a discrepancy by evaluating quantification methods that do not assume that cerebellar VT = VND, or account for the discrepancy between the two post-analysis. Similar..."

CNS Disorders

Neuroplasticity and neurotrophism in third-generation antipsychotics (ECNP 2025) - "While second-generation antipsychotics (SGAs) have shown some neuroprotective potential, the extent to which third-generation antipsychotics (TGAs) modulate neurotrophic pathways remains unclear.TGAs, such as brexpiprazole, cariprazine, lurasidone, pimavanserin, lumateperone, roluperidone,and iloperidone, are characterized by distinct receptor-binding profiles and are hypothesized to exert more targeted effects on synaptic plasticity, neurogenesis, and cognitive functions.Aims: This review aimed to systematically map and critically evaluate the available preclinical and clinical evidence regarding the neurotrophic and neuroplastic properties of TGAs, with a specific focus on their impact on brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF),glial cell line-derived neurotrophic factor (GDNF), and synaptic biomarkers. A scoping review was conducted according to PRISMA-ScR guidelines...Preclinical data indicated that brexpiprazole enhanced NGF-induced..."

CNS Disorders • Depression • Mental Retardation • Psychiatry • Schizophrenia • GFAP

Pimavanserin for the treatment of irritability associated with autism spectrum disorder in children and adolescents: a randomised, double-blind, placebo-controlled study (ECNP 2025) - P2/3 | "Pimavanserin did not demonstrate statistically significant improvement vs placebo in primary or secondary efficacy endpoints for irritability in children or adolescents with ASD. Pimavanserin was well tolerated in this population."

Clinical • CNS Disorders

Acadia Pharmaceuticals Inc...announced one late-breaker oral platform presentation and two poster presentations to be presented at the International Congress of Parkinson’s Disease and Movement Disorders being held October 5-9, 2025, in Honolulu, Hawaii. (Yahoo Finance) - "The presentations highlight updates from the company’s robust pipeline including preclinical efficacy, safety and mechanism of action findings on Acadia’s investigational drug ACP-711, under development for essential tremor, as well as a report on the study design of the Phase 2 ACP-204 study in adults with Lewy body dementia psychosis. The company will also present encore findings from a post-hoc analysis of clinical trial data evaluating duration of illness and response to NUPLAZID (pimavanserin) in Parkinson’s disease psychosis."

Clinical protocol • Preclinical • Retrospective data • Dementia • Essential Tremor • Lewy Body Disease • Parkinson's Disease

Pimavanserin -induced decreased appetite and weight loss: A case report. (PubMed, Indian J Psychiatry) - No abstract available

Journal

CAMELOT: Comparing Antipsychotic Medications in LBD Over Time (clinicaltrials.gov) - P4 | N=94 | Recruiting | Sponsor: The University of Texas Health Science Center at San Antonio | Trial completion date: Feb 2026 ➔ Feb 2027 | Trial primary completion date: Aug 2025 ➔ Aug 2026

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease • Psychiatry

C-SAPP: Pimavanserin vs. Quetiapine for Treatment of Parkinson's Psychosis (clinicaltrials.gov) - P4 | N=358 | Recruiting | Sponsor: VA Office of Research and Development | Trial completion date: Aug 2026 ➔ Aug 2027 | Trial primary completion date: Oct 2025 ➔ Oct 2026

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Posttraumatic Stress Disorder Psychopharmacology Algorithm Update-2024-2025. (PubMed, Psychiatry Clin Psychopharmacol) - "Prazosin remains the first-line treatment for PTSD-related sleep impairment, including nightmares and disturbed awakenings, and it may be useful for individuals with comorbid alcohol use disorder and comorbid headaches. After treating PTSD insomnia, if significant daytime symptoms remain, a selective serotonin reuptake inhibitor ( SSRI, sertraline or paroxetine are suggested), and this may be augmented by an antipsychotic (consider aripiprazole first) if psychotic symptoms, if any, do not respond to the SSRI...This update also evaluates emerging treatments, including transcranial magnetic stimulation, direct current stimulation, stellate ganglion block, and pimavanserin, though concluding that current evidence does not yet warrant their inclusion in the core algorithm. This update provides clinicians with an evidenceinformed approach to pharmacological PTSD management based on the latest available data."

Journal • Review • Addiction (Opioid and Alcohol) • CNS Disorders • Insomnia • Mood Disorders • Pain • Post-traumatic Stress Disorder • Sleep Disorder

TSL-CM-JSSPMFSL-Ⅲ: A Study of the Safety and Efficacy of Pimavanserin in Patients With Parkinson's Disease Psychosis (clinicaltrials.gov) - P3 | N=248 | Recruiting | Sponsor: Tasly Pharmaceutical Group Co., Ltd | Trial primary completion date: Jun 2025 ➔ Oct 2025

Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Synthesis and evaluation of novel 5-HT2A receptor inverse agonist with excellent in vivo antipsychotic efficacy and superior tissue distribution for treatment of Parkinson's disease psychosis. (PubMed, Eur J Med Chem) - "Pimavanserin is a 5-HT2A receptor inverse agonist as the first and only drug approved for the treatment of Parkinson's disease psychosis (PDP), which has a black box warning regarding an increased risk of death in elderly patients with dementia-related psychosis and warning related to QTc interval prolongation. Compound P25a demonstrated higher functional activities in both DOI-induced head twitches model and MK801-induced hyperactivity model. In conclusion, the enhanced in vitro and in vivo efficacy profiles, minimal hERG inhibition, and superior tissue distribution, established compound P25a as a promising preclinical candidate for treatment of PDP that warranted further investigation."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • Movement Disorders • Parkinson's Disease • Psychiatry

Characterization of the Serotonin 2A Receptor Selective PET Tracer [18F]MH.MZ in Patients With Neurodegenerative Diseases (clinicaltrials.gov) - P4 | N=75 | Recruiting | Sponsor: Vanderbilt University Medical Center | Trial completion date: Aug 2025 ➔ Aug 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Recommendations for management and future investigation of psychosis in neurodegenerative disease: Findings from the International Psychogeriatric Association (IPA) working group. (PubMed, Int Psychogeriatr) - "Future directions include the need for the implementation of evidence-based nonpharmacological treatments consistent with the aims of precision medicine, further investigation into novel pharmacological agents, mapping specific psychotic symptoms to specific biomarkers, and further exploration of the link between psychosis in neurodegenerative disease and other late-life psychoses."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Psychiatry • Schizophrenia

Subjectively reported sleep improvement with antipsychotic medications in clinical practice: A systematic review, meta-analysis and meta-regression of moderating factors. (PubMed, J Psychopharmacol) - "APs, mostly SGAs, improved sleep quality more than placebo, and this effect was more pronounced in anxiety disorders, for anti-histaminergic APs, and in longer trials. These results could add another important tile to the mosaic of precision medicine for prescribing APs."

Journal • Retrospective data • Review • CNS Disorders • Insomnia • Mental Retardation • Mood Disorders • Psychiatry • Sleep Disorder

Duration of Illness and Response to Pimavanserin in Parkinson's Disease Psychosis: Post-Hoc Analysis of Clinical Trial Data (ASCP 2025) - "Our analysis found that, at all levels of response, a greater percentage of patients with PDP responded to pimavanserin when treated <6 months after initial psychotic symptoms compared with patients treated ≥6 months after initial psychotic symptoms (complete response: 30.8% vs 11.0%); findings were consistent for durations of <12 vs ≥12 months since initial symptoms. Learning Objectives: Learning Objective 1 Examine individual responses to treatment with pimavanserin in patients with Parkinson's disease psychosis initiating treatment <6 months vs ≥6 months and <12 months vs ≥12 months after initial psychotic symptoms. Learning Objective 2 Discuss the significance of individual response data in clinical practice and how it may hold greater relevance for patient care."

Clinical • Retrospective data • CNS Disorders • Parkinson's Disease • Psychiatry

PANDER: Investigating the Neuropsychological Effects of 5-HT2a Antagonism (clinicaltrials.gov) - P=N/A | N=80 | Recruiting | Sponsor: University of Oxford

New trial