Nuplazid (pimavanserin) / Acadia Pharma - LARVOL DELTA

Leptin augments the hypercapnic ventilatory response (HCVR) via the 5-HT pathway (Neuroscience 2026) - "In Experiment 1, leptin did not affect VE under normocapnia but increased minute ventilation under hypercapnic conditions in the absence of pimavanserin. Pimavanserin had no effect on ventilation at normocapnia but markedly attenuated the HCVR regardless of leptin treatment. The combination of leptin and pimavanserin significantly suppressed normocapnic breathing."

CNS Disorders • LEP

Serotonergic signaling in high-grade glioma: electrophysiological evidence for bidirectional communication (Neuroscience 2026) - "Exogenous serotonin evoked slow inward currents in glioma monoculture cells consistent with GPCR-mediated signaling, which were blocked by the 5-HT2A receptor antagonist pimavanserin. In xenografted acute slice preparations, bath application of serotonin also increased the amplitude of voltage-gated calcium channel-mediated currents.Together, these findings demonstrate glioma-induced changes in dorsal raphe neuron activity and identify molecular mechanisms through which serotonin affects glioma electrophysiology, highlighting possible therapeutic targets."

CNS Disorders

On the road to personalized therapy: 3D-printed nanostructured orodispersible films for repurposed anticancer drug delivery in pediatric oncology. (PubMed, Int J Pharm) - "The aim of this study was to develop and characterize a three-dimensional (3D)-printed orodispersible film (ODF) using semi-solid extrusion (SSE), intended for the administration of pimavanserin (PIMA) and celecoxib (CXB), selected as repurposed anticancer agents, previously encapsulated in nanostructured lipid carriers (NLCs), for pediatric oncology. Infill density also strongly affected drug release: at 120 min, PIMA release ranged from 44% (100% infill) to over 97% (50% infill), showing that infill modulation alone enables predictable adjustment of dose, disintegration, and release kinetics without altering ink composition. This study reports the first formulation that combines pre-encapsulated PIMA and CXB in NLCs within a 3D-printed ODF using SSE, thereby constituting a promising platform for personalized pediatric drug delivery."

Journal • Oncology • Pediatrics

Reducing Daytime Sedation While Preserving Motor Function in Parkinson's Disease Psychosis: A Case Report of Psychotropic Timing and Deprescribing. (PubMed, Cureus) - "Morning alertness improved, with increased participation in therapy sessions, while motor function remained stable. This case highlights an individualized approach to balancing behavioral control, daytime alertness, and motor preservation in PD psychosis while illustrating how cumulative sedative burden and medication timing may influence functional outcomes."

Journal • Anesthesia • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Treatment-resistant Parkinson's disease psychosis responding to xanomeline-trospium: A case report. (PubMed, Clin Park Relat Disord) - "He was referred specifically for a trial of clozapine therapy, which the patient and caregiver declined due to its risk profile. The patient's psychosis proved refractory to three pharmacologically distinct therapies-quetiapine, a low-affinity, rapidly dissociating dopamine D2 receptor antagonist; brexpiprazole, a dopamine D2 partial agonist; and pimavanserin, a selective 5-HT2A receptor inverse agonist-before improving with xanomeline-trospium, whose antipsychotic effects are mediated through central M1/M4 muscarinic receptor agonism. This case supports the further investigation of muscarinic receptor agonism as a therapeutic strategy for Parkinson's disease psychosis."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • DRD2

Treatment of Parkinson's Disease-Related Psychosis. (PubMed, Clin Pharmacol) - "When antipsychotic therapy is required, pimavanserin and clozapine demonstrate the strongest evidence for efficacy...Quetiapine is widely used despite inconsistent evidence from randomized trials, largely due to its favorable safety profile and ease of use...Current therapeutic strategies allow symptom control in many patients, yet important gaps in the evidence base persist, particularly regarding long-term outcomes. Future research should prioritize mechanistically informed therapies, standardized outcome measures, and the identification of predictors of treatment response."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Update on Parkinson's Disease Psychosis: Epidemiology, Mechanisms and Management. (PubMed, Neurol Ther) - "Pimavanserin and clozapine are the only pharmacologic therapies for PDP that have been found to be efficacious in randomized controlled trials, though quetiapine is most frequently used despite lacking positive trial results. Future research that continues to clarify the exact pathophysiology of psychosis in PD will improve the current therapeutic approaches, and ongoing randomized clinical trials of these therapies are necessary to identify the safest and most efficacious treatments for PD patients with psychosis."

Clinical • Journal • Review • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Symptomatic treatment for Alzheimer disease: current evidence and future directions. (PubMed, Nat Rev Neurol) - "Established pharmacological treatments, notably cholinesterase inhibitors and memantine, deliver modest but significant benefits, with biomarker-stratified analyses suggesting the greatest benefit in individuals with confirmed AD pathology...Newer agents, including brexpiprazole for agitation and pimavanserin for psychosis, show promise but require careful interpretation of effect size and safety. Future progress will depend on biomarker-informed patient selection, integration of circuit-level measures, rational combination strategies spanning pharmacological and non-pharmacological modalities, and adoption of patient-centred outcomes. Symptomatic therapies will remain essential for improving quality of life in people with AD, even as disease-targeted therapies reshape disease trajectories."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Psychiatry

Pimavanserin for Rigid-compulsive Symptoms in Autism Spectrum Disorder (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: New York State Psychiatric Institute | Trial completion date: Dec 2026 ➔ Dec 2027 | Trial primary completion date: Dec 2026 ➔ Oct 2027

Trial completion date • Trial primary completion date • Autism Spectrum Disorder • Genetic Disorders

An Open-Label Study Investigating the 5-HT2A Receptor Occupancy of Remlifanserin (ACP-204) With the PET Radioligand [18F]Altanserin in Healthy Male Participants. (PubMed, Clin Pharmacol Drug Dev) - "Remlifanserin (ACP-204) is a selective 5-HT2A receptor inverse agonist that builds upon scientific findings of its structural analog, pimavanserin. Single doses of remlifanserin were safe and well tolerated. Study findings will inform the development and dosing of remlifanserin in future Phase 2/3 trials."

Journal

PRISMatic: Psilocybin Efficacy With or Without Pimavanserin Pretreatment (clinicaltrials.gov) - P1/2 | N=20 | Recruiting | Sponsor: Johns Hopkins University | Initiation date: Jul 2026 ➔ Sep 2026

Trial initiation date

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 2027 ➔ Aug 2028 | Trial primary completion date: Oct 2026 ➔ Oct 2027

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

Acadia Pharmaceuticals Reports Second Quarter 2026 Financial Results (Businesswire) - "GAAP net product sales of NUPLAZID were $183 million for the second quarter of 2026, up 9% compared to GAAP net product sales of $168 million for the second quarter of 2025, and up 10% as compared to non-GAAP adjusted net product sales of $166 million for the second quarter of 2025. Net product sales of DAYBUE were $125 million for the second quarter of 2026, an increase of 30% as compared to $96 million for the second quarter of 2025."

Sales • CNS Disorders • Genetic Disorders • Parkinson's Disease • Rare Diseases

Emerging pharmacological and neuromodulation interventions for suicidal ideation and behaviour. (PubMed, Eur Neuropsychopharmacol) - "Encouraging results were reported for NMDA-related drugs (NRX-101 and high-dose d-cycloserine; amantadine in Borna disease virus-1-positive depression), opioid-system modulation (buprenorphine at ultra-low and high doses in distinct populations), ayahuasca in major and treatment-resistant depression, and adjunctive pimavanserin. Smaller effects were observed for vortioxetine augmentation and insomnia-targeted zolpidem. Large observational datasets reported associations between lower suicidality and folic acid, benztropine, testosterone initiation in transgender adults, and non-vitamin K oral anticoagulants versus warfarin, whereas non-medical cannabis use was associated with worse SI trajectories. Neuromodulation evidence implicated accelerated or targeted repetitive transcranial magnetic stimulation, theta-burst stimulation, and magnetic seizure therapy for SI reduction, with longer-term observational support for vagus nerve stimulation. Future trials should prespecify..."

Journal • Review • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Epilepsy • Insomnia • Psychiatry • Sleep Disorder • Suicidal Ideation

PRISMatic: Psilocybin Efficacy With or Without Pimavanserin Pretreatment (clinicaltrials.gov) - P1/2 | N=20 | Recruiting | Sponsor: Johns Hopkins University | Not yet recruiting ➔ Recruiting

Enrollment open

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 2026 ➔ Aug 2027 | Trial primary completion date: Jun 2026 ➔ Jun 2027

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

Effects of pimavanserin, xanomeline and highly-purified plant-derived cannabidiol on MK-801-induced behaviours in mice relevant to psychosis. (PubMed, J Psychopharmacol) - "These results suggest that hpCBD, like PIM and XAN, demonstrates putative antipsychotic-like activity in classic mouse assays relevant to psychosis, consistent with positive clinical data in patients with psychosis."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia • DRD2

Impact of Pimavanserin on Longitudinal Trajectories of Parkinson’s Disease Psychosis and Cognitive Symptoms (EAN 2026) - "Treatment options are limited, with clozapine constrained by safety concerns, quetiapine demonstrating variable efficacy, and pimavanserin approved specifically for PDP but unavailable outside of the U.S. Long-term real-world data on treatment effects are scarce. Pimavanserin was associated with long-term attenuation of psychosis and cognitive symptom progression in this real-world cohort, exceeding effects observed with other treatments."

CNS Disorders • Cognitive Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Dextromethorphan/bupropion (Auvelity) for agitation in Alzheimer's dementia. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Alzheimer's Disease • CNS Disorders • Dementia

Impact of baseline sleep disturbances on Pimavanserin response in Parkinson’s disease psychosis: A post hoc analysis (WPC 2026) - P3 | "Pimavanserin demonstrated consistent antipsychotic efficacy vs placebo in patients with PDP regardless of baseline sleep-disturbance status. Additionally, patients with baseline impairment in nighttime sleep experienced improved nighttime sleep with pimavanserin. These findings support the consistent efficacy of pimavanserin in the presence or absence of daytime or nighttime sleep disturbance."

Retrospective data • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • Sleep Disorder

Response trajectories of patients with Parkinson’s disease psychosis treated with Pimavanserin: An exploratory cluster analysis (WPC 2026) - "Although many patients from each of the 5 most common input clusters appeared in the improvement/response output clusters, overall, individual clinical outcome trajectories varied. Patients with similar baseline profiles may follow very different response trajectories, further highlighting the heterogeneity in PDP and underscoring the need for more personalized, patient-centered care. This abstract will have been previously presented at the American Academy of Neurology (AAN) 2026 Annual Meeting, April 18-22, 2026; Chicago, Illinois."

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

Nonclinical characterization of ACP-204, a novel selective serotonin receptor subtype 2A receptor inverse agonist. (PubMed, J Pharmacol Exp Ther) - "Pimavanserin was the first US Food and Drug Administration approved antipsychotic drug that does not block D2 dopamine receptors at therapeutic doses. ACP-204 is a novel 5-HT2A receptor inverse agonist/antagonist being evaluated clinically for its potential to treat Alzheimer disease psychosis and Lewy body dementia psychosis. Comprehensive nonclinical evaluations shown herein demonstrate that ACP-204 has optimized pharmacodynamic properties resulting in a favorable safety/tolerability profile, a broad therapeutic index, and promising effectiveness."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia • DRD2 • NAV1

PRISMatic: Psilocybin Efficacy With or Without Pimavanserin Pretreatment (clinicaltrials.gov) - P1/2 | N=20 | Not yet recruiting | Sponsor: Johns Hopkins University

New P1/2 trial

Pimavanserin for Irritability in Children and Adolescents With Autism Spectrum Disorder: Phase 2 Randomized Trial. (PubMed, J Am Acad Child Adolesc Psychiatry) - P2/3 | "Pimavanserin was well tolerated, but selected doses were not demonstrated to be efficacious compared with placebo for the short-term treatment of irritability in children or adolescents with ASD."

Journal • P2 data • Autism Spectrum Disorder • Genetic Disorders

Pimavanserin for non-Parkinsonian dementia-related psychosis: A systematic review of efficacy safety and tolerability (APA 2026) - P2 | "Pimavanserin demonstrates clinically meaningful efficacy in reducing psychotic symptoms and preventing relapse in dementia-related psychosis while maintaining a relatively favorable safety and tolerability profile. These findings support pimavanserin as a promising therapeutic option in this high-risk population and highlight the need for further trials to confirm long-term benefits."

Clinical • Review • Alzheimer's Disease • CNS Disorders • Constipation • Dementia • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Movement Disorders • Nephrology • Parkinson's Disease • Psychiatry