iloperidone / Generic mfg. - LARVOL DELTA

Clinical Evaluation of Bysanti: A New Atypical Antipsychotic for Schizophrenia and Bipolar I Disorder. (PubMed, Ann Pharmacother) - "Milsaperidone represents an incremental yet meaningful addition to antipsychotic therapy, supporting individualized strategies in schizophrenia and bipolar I disorder while balancing efficacy and tolerability."

Journal • Review • Anesthesia • Bipolar Disorder • CNS Disorders • Hypotension • Mood Disorders • Psychiatry • Schizophrenia

Milsaperidone: First Approval. (PubMed, Clin Drug Investig) - "Milsaperidone is an active metabolite of iloperidone (Fanapt®), an atypical antipsychotic approved in the USA for the treatment of schizophrenia since 2009 and for use in the acute treatment of bipolar I disorder since 2024...Additionally, milsaperidone is in phase III clinical evaluation for use in the treatment of major depressive disorder. This article summarizes the milestones in the development of milsaperidone leading to this first approval for schizophrenia and bipolar I disorder in adults."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Schizophrenia

Risk of Akathisia with Antipsychotics and Its Treatment: Is Propranolol still the best option in 2025? (APA 2026) - " We performed a literature review using PubMed and PubMed Central databases using keywords in different combinations, like "akathisia and antipsychotics", "akathisia management", "akathisia and propranolol", "akathisia and ECT", "akathisia and benzodiazepines", "akathisia and mirtazapine", "akathisia and biperiden/anticholinergics", and "akathisia and vitamin B6" etc. We included data from thirty-nine observational, analytical, and review articles published in the last five years and summarized the key findings. Observations: Akathisia has been classically associated with first-generation high-potency antipsychotics like haloperidol. Among atypical antipsychotics Risperidone (mean dose of 5.4mg/day) and Lurasidone (mean dose of 240mg/day), Cariprazine and Ziprasidone have been found causing akathisia at higher therapeutic dosages, while the risk is found to be lower with Sertindole..."

CNS Disorders

Iloperidone treatment mitigates the Juvenile Huntington's Disease phenotype possibly via Sigma-1 Receptor Modulation. (PubMed, FEBS J) - "Consistently, the two ligands exerted opposite effects on S1R oligomerization in vitro. Overall, the integration of experimental and computational data supports a model in which iloperidone behaves as an S1R agonist, promoting receptor dissociation and phenotypic recovery through modulation of proteostasis."

Journal • CNS Disorders • Genetic Disorders • Huntington's Disease • Movement Disorders

A potential association of SLC2A9 variant rs7442295 with uric acid at baseline and in interaction with iloperidone. (PubMed, Pharmacogenomics J) - "Overall, the mechanism of this iloperidone-induced increase in serum urate levels is likely due to decrease in clearance of urate through interaction with the SLC2A9 urate transporter protein. These results may hold clinical significance for patients treated with iloperidone."

Clinical • Journal • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry • Schizophrenia

From Neuropsychiatric Use to Oncology: Repurposing Antipsychotic Drugs for Cancer Treatment. (PubMed, Eur J Pharmacol) - "Antipsychotics such as chlorpromazine, haloperidol, iloperidone, and risperidone have demonstrated notable activity, primarily against colon, breast, lung, and brain cancers, while evidence in myeloma, lymphoma, and melanoma remains limited. Notably, several agents exhibit synergistic effects when combined with standard chemotherapeutics, including doxorubicin and temozolomide, and may improve sensitivity to chemotherapy and radiotherapy. However, approximately 80% of available studies are confined to in vitro models, highlighting the need for robust in vivo and clinical investigations to validate their translational potential."

Journal • Review • Brain Cancer • CNS Disorders • Hematological Malignancies • Lymphoma • Melanoma • Multiple Myeloma • Oncology • Psychiatry • Solid Tumor

Vanda Pharmaceuticals Reports…Full Year 2025 Financial Results (PRNewswire) - "Total net product sales from Fanapt, HETLIOZ and PONVORY were $216.1 million for the full year 2025, a 9% increase compared to $198.8 million for the full year 2024. Fanapt net product sales were $117.3 million for the full year 2025, a 24% increase compared to $94.3 million for the full year 2024. HETLIOZ net product sales were $71.4 million for the full year 2025, a 7% decrease compared to $76.7 million for the full year 2024. PONVORY net product sales were $27.4 million for the full year 2025, a 2% decrease compared to $27.8 million for the full year 2024."

Commercial • Bipolar Disorder • Mood Disorders • Multiple Sclerosis • Psychiatry • Schizophrenia • Sleep Wake Cycle Disorder

Vanda Pharmaceuticals Reports Fourth Quarter…Financial Results (PRNewswire) - "Total net product sales from Fanapt, HETLIOZ and PONVORY were $57.2 million in the fourth quarter of 2025, an 8% increase compared to $53.2 million in the fourth quarter of 2024. Fanapt net product sales were $33.2 million in the fourth quarter of 2025, a 25% increase compared to $26.6 million in the fourth quarter of 2024. HETLIOZ net product sales were $16.4 million in the fourth quarter of 2025, an 18% decrease compared to $20.0 million in the fourth quarter of 2024. PONVORY net product sales were $7.6 million in the fourth quarter of 2025, a 17% increase compared to $6.5 million in the fourth quarter of 2024."

Commercial • Sales • Bipolar Disorder • Mood Disorders • Multiple Sclerosis • Psychiatry • Schizophrenia • Sleep Wake Cycle Disorder

Discovery of F-18 labeled repurposed CNS drugs by computational strategy for effective tau imaging and alzheimer's diagnosis. (PubMed, PLoS One) - "Drug 416 (reported BRAF inhibitor, RG6344) shows a binding free energy of ΔG = -7.91 kcal/mol, while Drug 610 (Iloperidone/HP 873), a D2/5-HT2 receptor antagonist, exhibits a predicted binding free energy of ΔG = -6.88 kcal/mol with the target Tau protein respectively. The F-18 label enabled real-time PET imaging, allowing non-invasive tracking of the drug's binding to Tau in the brain. Our approach provides a comprehensive solution to the current limitations in Alzheimer's diagnosis by offering F-18 labeled drugs that effectively target Tau protein without compromising their biological activity, advancing both diagnostic and therapeutic strategies for AD."

Journal • Alzheimer's Disease • CNS Disorders

Evaluation of Efficacy and Safety of Iloperidone for the Treatment of Participants With Uncontrolled Hypertension (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Vanda Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Hypertension

Simultaneous determination of iloperidone and its metabolites in rat plasma using a novel UPLC-MS/MS method: an application for drug-drug interaction. (PubMed, BMC Pharmacol Toxicol) - "The data demonstrated that shikonin obviously changed the main pharmacokinetics of ILP and its metabolites in rats. In the future clinical use, we should pay more attention to the concomitant application of shikonin and ILP in humans."

Journal • Preclinical • CYP3A4

QT interval prolongation in acute antipsychotic poisoning: systematic review and recommendations. (PubMed, Clin Toxicol (Phila)) - "Individual medication recommendations were made for amisulpride (15 articles), thioridazine (11 articles), ziprasidone (eight articles) and quetiapine (13 articles), whilst consensus statements based on limited data were made for acute ingestions of clozapine, haloperidol, iloperidone, pimozide, pipamperone, olanzapine and risperidone (14 articles in total). The QT Interval Prolongation in Clinical Toxicology Workgroup suggests the same approach for patients with overdoses of haloperidol, iloperidone, pipamperone and pimozide. The risk of torsade de pointes is likely overstated for acute antipsychotic medication overdose as a general class group, and concern should rather focus on a few specific medications."

Journal • CNS Disorders

Pharmacogenetic Guidelines and Resources to Support Antidepressant and Antipsychotic Use in Child and Adolescent Psychiatry (AACAP 2025) - "The FDA categorizes drug-gene pairs by implications on therapeutic management, safety, or pharmacokinetics. If a patient has genotype results available, the CPIC and/or FDA currently provide assessments supporting the utility of PGx to inform the use of many antidepressants including es/citalopram (CYP2C19), fluvoxamine (CYP2D6), paroxetine (CYP2D6), sertraline (CYP2C19 and CYP2B6), TCAs (CYPC19 and/or CYP2D6), venlafaxine (CYP2D6), and vortioxetine (CYP2D6)...FDA labeling provides specific dosing based on CYP2D6 poor metabolizer genotypes for aripiprazole, brexpiprazole, iloperidone, pimozide, and thioridazine... CPIC and FDA resources are useful for identifying evidence-based PGx information for commonly used antidepressants and antipsychotics. PharmGKB and Sequence2Script support access to foundational literature and the clinical implementation of PGx results.PPC, ADP, APS"

Biomarker • Clinical • CNS Disorders • Psychiatry • CYP19A1 • CYP2C19 • HTR2A • SLC6A4

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

Pharmacological fingerprints of polypharmacy with dopamine receptor partial agonists in combination with the "-dones" (risperidone, paliperidone, ziprasidone, iloperidone) (ECNP 2025) - "Methods We reviewed pharmacological properties of three DRPAs – aripiprazole (ARI), brexpiprazole (BRX), and cariprazine (CAR) – and four "-dones" – risperidone (RIS), paliperidone (PAL), ziprasidone (ZIP) and iloperidone (ILO).(2-4) Results DRPAs' half-life is longer (3 days-1 week) than that of the -dones' (7-33 hours)...Metabolic pathways are mostly shared: CYP3A4 and 2D6, thus, even more attention should be paid to avoiding the co-administration of enzyme inhibitors (e.g., carbamazepine, grapefruit juice, fluoxetine)...A generally positive advantage as seen in case of DRPA+pines (clozapine, olanzapine, quetiapine) cannot be postulated for DRPA+dones, however, the neuroreceptor complementarity is most clearcut with CAR vs. ARI & BRX. Keywords: dopamine receptor partial agonists, antipsychotic polypharmacy, combination, receptor profile"

Combination therapy • CNS Disorders • Psychiatry • Schizophrenia • CYP3A4

Pharmacokinetic Study of VHX-896 and Iloperidone Tablets Under Steady-State Conditions (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: Vanda Pharmaceuticals | Not yet recruiting ➔ Completed

Trial completion • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia

Randomized Withdrawal Study in Patients With Schizophrenia (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Vanda Pharmaceuticals | Not yet recruiting ➔ Recruiting | N=200 ➔ 400

Enrollment change • Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

Antipsychotic-Related Prolactin Changes: A Systematic Review and Dose-Response Meta-analysis. (PubMed, CNS Drugs) - "The prolactin-increasing property varies among antipsychotics, is dose-related, and is greater in females. These findings in adults with acutely exacerbated schizophrenia can help clinicians titrate and adapt antipsychotic doses and consider patients' sex in treatment decisions. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO); registration no. CRD42020181467."

Journal • Retrospective data • Review • CNS Disorders • Psychiatry • Schizophrenia

Sexual dysfunctions related to use of antipsychotics: A protocol for a systematic review and meta-analysis. (PubMed, PLoS One) - "The antipsychotic medications of interest are amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, chlorpromazine, clopenthixol, clozapine, droperidol, flupenthixol, fluphenazine, haloperidol, iloperidone, levomepromazine, loxapine, lurasidone, molindone, olanzapine, paliperidone, penfluridol, perphenazine, perazine, pimozide, prochlorperazine, quetiapine, risperidone, sertindole, sulpiride, thiothixene, thioridazine, trifluoperazine, ziprasidone, zuclopenthixol and zotepine. The Cochrane Risk of Bias tool and RoB 2.0 will be used to assess the risk of bias in studies. We will evaluate the quality of the evidence contributing to network estimates for the primary outcomes using the GRADE framework, and key factors that may affect the observed effects will be analysed for consistency across studies."

Journal • Retrospective data • CNS Disorders • Sexual Disorders • PRL

Evaluation of Efficacy and Safety of Iloperidone for the Treatment of Participants With Uncontrolled Hypertension (clinicaltrials.gov) - P2 | N=240 | Not yet recruiting | Sponsor: Vanda Pharmaceuticals

New P2 trial • Cardiovascular • Hypertension

Strategies for Switching between Oral Postsynaptic Antidopaminergic Antipsychotics in Patients with Schizophrenia: A Systematic Review. (PubMed, CNS Drugs) - "Despite the importance and frequency of antipsychotic switching, few studies have specifically investigated outcomes of different switch strategies. General clinical preference appears to utilize gradual switching approaches to avoid potential rebound symptoms. Future research with current and emerging antipsychotics is needed, especially for switching between antipsychotics with different receptor profiles and for switches that are potentially vulnerable to rebound and withdrawal symptoms."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

Unsupervised Graph Clustering Reveals a Clinical Taxonomy of Antipsychotics (APA 2025) - "Cluster 1 contained Aripiprazole, Brexpiprazole, Cariprazine, Lurasidone, Sertindole, and Ziprasidone, and was characterized by an excellent side-effect profile but also with the lowest efficacy. Cluster 2 contained Chlorpromazine, Haloperidol, Loxapine, Molindone, Perphenazine, and Thiothixene, and showed strong efficacy in positive symptoms, but also had a high-risk for EPS, QTc prolongation and seizures. Cluster 3 contained Clozapine, Iloperidone, Olanzapine, Quetiapine, Thioridazine, and Zotepine, and showed strong overall efficacy but carried the highest risk for sedation and metabolic side effects. Cluster 4 contained Amisulpride, Asenapine, Paliperidone, Risperidone, and Sulpride, and showed excellent positive and negative symptom efficacy but carried the highest risk of hyperprolactinemia. Cluster 5 contained Flupentixol, Fluphenazine, Pimozide, and Trifluoperazine and showed the lowest efficacy with a high risk of causing EPS. Conclusion Despite traditional..."

Clinical • Anesthesia • CNS Disorders • Epilepsy • Hypotension • Psychiatry • Schizophrenia

Vanda Pharmaceuticals Reports First Quarter 2025 Financial Results (PRNewswire) - "Total net product sales from Fanapt, HETLIOZ and PONVORY were $50.0 million in the first quarter of 2025, a 5% increase compared to $47.5 million in the first quarter of 2024. Fanapt net product sales were $23.5 million in the first quarter of 2025, a 14% increase compared to $20.6 million in the first quarter of 2024. HETLIOZ net product sales were $20.9 million in the first quarter of 2025, a 4% increase compared to $20.1 million in the first quarter of 2024. PONVORY net product sales were $5.6 million in the first quarter of 2025, a decrease of 18% compared to $6.8 million in the first quarter of 2024."

Sales • Bipolar Disorder • Multiple Sclerosis • Sleep Disorder • Sleep Wake Cycle Disorder

Open-Label Evaluation of Relapse Prevention in Patients With Schizophrenia (clinicaltrials.gov) - P3 | N=200 | Not yet recruiting | Sponsor: Vanda Pharmaceuticals

New P3 trial • CNS Disorders • Psychiatry • Schizophrenia

Activity of GPCR-targeted drugs influenced by human gut microbiota metabolism. (PubMed, Nat Chem) - "We also observed iloperidone inactivation by generating unconventional metabolites. The human gut commensal bacteria mixture incorporated sulfur in the form of a thiophene motif, whereas Morganella morganii used a cascade reaction to incorporate amino-acid-derived tricyclic systems into the drug metabolites. Our results reveal a broad impact of human gut commensal bacteria on GPCR-targeted drug structures and activities through diverse microbiota-mediated biotransformations."

Journal