iloperidone / Generic mfg. - LARVOL DELTA

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

Third-Generation Antipsychotics: The Quest for the Key to Neurotrophism. (PubMed, Life (Basel)) - "While second-generation antipsychotics (SGAs) are associated with a better side effect profile than their predecessors, the emergence of third-generation antipsychotics (TGAs)-such as brexpiprazole, cariprazine, lurasidone, iloperidone, lumateperone, pimavanserin, and roluperidone-has prompted renewed interest in their potential neuroprotective and pro-cognitive effects. Although data remain limited and focused primarily on earlier SGAs, emerging findings suggest that some TGAs may exert positive effects on neuroplastic processes, including the modulation of brain-derived neurotrophic factors (BDNFs) and synaptic architecture. However, robust clinical data on their long-term effects and comparative efficacy are lacking; therefore, further research is necessary to validate their role in preventing neurodegenerative changes and improving cognitive outcomes in patients with psychiatric conditions."

Journal • Review • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia • BDNF

Antipsychotic drug dosing and study discontinuation in schizophrenia: A systematic review and dose-response meta-analysis. (PubMed, Eur Neuropsychopharmacol) - "Dose discontinuation curves varied between the antipsychotics and included U-shaped, monotonic, and hyperbolic patterns. Future studies should consistently present disease-related and side-effect-related dropouts due to adverse events separately."

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

Safety and Tolerability of Open-Labeled Iloperidone in Adolescents (clinicaltrials.gov) - P4 | N=100 | Recruiting | Sponsor: Vanda Pharmaceuticals | Trial completion date: Sep 2024 ➔ Nov 2026 | Trial primary completion date: Sep 2024 ➔ Mar 2026

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

Vanda Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results (PRNewswire) - "Total net product sales from Fanapt, HETLIOZ and PONVORY were $53.2 million in the fourth quarter of 2024, a 17% increase compared to $45.3 million in the fourth quarter of 2023 and a 12% increase compared to $47.7 million in the third quarter of 2024."

Sales • CNS Disorders

Lurasidone versus typical antipsychotics for schizophrenia. (PubMed, Cochrane Database Syst Rev) - "We are very uncertain about whether lurasidone offers benefits to the mental state, total serious adverse events, or severe adverse events when compared to typical antipsychotics for people with schizophrenia. The evidence included in this review is of very low certainty, derived from two small trials. Study limitations (risk of bias) and imprecise results impacted our confidence in the evidence. Furthermore, data on mortality (due to suicide or natural causes) or quality of life are unavailable. Further large-scale randomized studies are needed to provide clearer insights into the benefits and harms of lurasidone compared to typical antipsychotics for treating schizophrenia."

Clinical • Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

An Evaluation of Iloperidone for Mania in Bipolar I Disorder. (PubMed, Ann Pharmacother) - "QTc prolongation is dose related, so drug interactions involving CYP2D6 and CYP3A4 inhibition can have serious consequences. In the pivotal trial, iloperidone was effective in treating adults with an acute manic or mixed episode associated with bipolar I disorder and was safe and well tolerated."

Journal • Review • Bipolar Disorder • Cardiovascular • CNS Disorders • Hypotension • Mood Disorders • Psychiatry • Xerostomia

Systematic Approach in the Development of Chitosan Functionalized Iloperidone Nanoemulsions for Transnasal Delivery, In Vitro and In Vivo Studies. (PubMed, AAPS PharmSciTech) - "Studies in RPMI 2650 nasal and Neuro2A brain cell line lines indicated safety of chitosan functionalized transnasal Iloperidone nanoemulsions. Studies in Wistar rats showed increased cataleptic effects, reduced cognitive impairment and anxiety-related behaviour with greater brain accumulation indicating promising potential of this approach in nose to brain drug delivery."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Mood Disorders • Psychiatry

Antipsychotic-induced prolactin variation: a systematic review and dose-response meta-analysis (ECNP 2024) - "Our dose-response curves depicted that the evolvement of prolactin in aripiprazole, cariprazine, and lumateperone had a negative relationship with the taken doses (the lowest point was -6.37ng/mL at 14.7mg/d, -3.40ng/mL at 8.7mg/d, -3.6ng/mL at 120mg/d, respectively). Quetiapine carried negligible risks for prolactin growth across examined doses (prolactin change between -0.87 to 1.55ng/mL within 1144mg/d). While most of the other antipsychotics had their risks of prolactin rise with increasing doses and then continued to step-up(the maximum point was asenapine 10.44ng/mL at 20mg/d, iloperidone 10.18ng/mL at 24mg/d, lurasidone 17.91ng/mL at 240mg/d, olanzapine 14.97ng/mL at 40mg/d, risperidone 159.92ng/mL at 12mg/d), plateaued(the maximum point was paliperidone 50.97ng/mL at 12mg/d, ziprasidone 8.07ng/mL at 200mg/d) or even declined(the maximum point for brexpiprazole was 2.11ng/mL at 1.7mg/d, haloperidol was 22.56ng/mL at 8.6mg/d)...However, the extent of prolactin..."

Retrospective data • Review • CNS Disorders • Psychiatry • Schizophrenia

Real-World Effectiveness, Economic, and Humanistic Outcomes of Selected Oral Antipsychotics in Patients with Schizophrenia: A Systematic Review Evaluating Global Evidence. (PubMed, Clinicoecon Outcomes Res) - "Our systematic review aimed to synthesize literature describing real-world effectiveness, economic, and humanistic outcomes of OATs (asenapine, brexpiprazole, cariprazine, iloperidone, lumateperone, lurasidone, olanzapine/samidorphan, paliperidone, and quetiapine) for successful management of the disease. Medication non-adherence and treatment discontinuation were predominant factors contributing to the economic burden of schizophrenia. Our research showcased a significant knowledge gap across OATs spanning the humanistic and behavioral outcomes and medication adherence and switching, suggesting a need for robust evidence generation to help clinicians and payers make informed decisions regarding treatment opportunities and cost-effective strategies for patients with schizophrenia."

Journal • Real-world • Real-world effectiveness • Real-world evidence • Review • CNS Disorders • Psychiatry • Schizophrenia