Caplyta (lumateperone) / J&J - LARVOL DELTA

Lumateperone Safety and Tolerability in Schizophrenia: A Narrative Review. (PubMed, Cureus) - "In particular, it appears to carry a lower risk of metabolic and motor side effects, which may support improved long-term adherence. Overall, this review aims to contextualize the emerging body of evidence and to evaluate the potential role of lumateperone, particularly for patients with inadequate response to conventional antipsychotics."

Journal • Review • Anesthesia • CNS Disorders • Psychiatry • Schizophrenia

Adjunctive Lumateperone in Patients With Major Depressive Disorder: Results From a Randomized, Double-Blind, Phase 3 Trial. (PubMed, Am J Psychiatry) - "Patients receiving lumateperone 42 mg plus ADT had statistically significant and clinically meaningful improvement in depression symptoms and disease severity compared with those receiving placebo+ADT. Lumateperone+ADT was generally safe and well tolerated in patients with MDD with inadequate ADT response."

Clinical • Journal • P3 data • CNS Disorders • Depression • Fatigue • Major Depressive Disorder • Mood Disorders • Psychiatry • Suicidal Ideation • Xerostomia

Reply: Statistical limitations of the claimed dose-response in "Dose-response efficacy and safety of lumateperone in bipolar depression: A preliminary meta-analysis of randomized controlled trials". (PubMed, J Psychopharmacol) - No abstract available

Journal • Retrospective data • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

Statistical limitations of the claimed dose-response in "Dose-response efficacy and safety of lumateperone in bipolar depression: A preliminary meta-analysis of randomized controlled trials". (PubMed, J Psychopharmacol) - No abstract available

Journal • Retrospective data • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

Probable Lumateperone-Associated Urticarial Rash in a Patient With Schizophrenia. (PubMed, Prim Care Companion CNS Disord) - No abstract available

Journal • CNS Disorders • Dermatology • Immunology • Psychiatry • Schizophrenia • Urticaria

Volumetric absorptive microsampling for lumateperone analysis: method validation and stability evaluation. (PubMed, Anal Bioanal Chem) - "Method reliability was successfully tested by comparing the VAMS performance with standard in-tube fluid plasma, and short- and medium-term comparative stability assays confirmed the enhancement of analyte stability obtained in dried microsamples with respect to plasma samples. This is the first analytical method based on microsampling able to provide reliable data when compared to plasma analysis and promising for future TDM applications in patients treated with lumateperone, thus offering significant advantages over conventional blood/plasma sampling in terms of collection, storage and processing."

Journal • CNS Disorders • Psychiatry • Schizophrenia

Efficacy and Safety of Cariprazine, Asenapine, Xanomeline-Trospium, and Lumateperone for Acute Exacerbations of Schizophrenia in Adults: A Network Meta-Analysis. (PubMed, Schizophr Bull Open) - "However, further head-to-head comparisons with standard treatments are needed to guide a more evidence-based selection. Future trials with longer durations and more diverse populations are warranted to confirm and extend these findings."

Journal • Retrospective data • CNS Disorders • Psychiatry • Schizophrenia

FDA approval of CAPLYTA (lumateperone) has the potential to reset treatment expectations, offering hope for remission in adults with major depressive disorder (PRNewswire) - "This approval is based on positive results from two Phase 3, global, double-blind, placebo-controlled trials – Study 501 and 502 – which both met their primary and key secondary endpoints..."

FDA approval • Major Depressive Disorder

Impact of selected second and third generation antipsychotics on cognitive dysfunction in schizophrenia-spectrum disorders. Systematic review and network meta-analysis. (PubMed, Int Clin Psychopharmacol) - "This study aimed to: (a) systematically review randomized controlled trials (RCTs) evaluating the cognitive effects of third-generation antipsychotics (TGAs: brexpiprazole, cariprazine, lumateperone, and lurasidone) and xanomeline-trospium; and (b) perform a network meta-analysis (NMA) including additional second-generation antipsychotics with potential procognitive effects. A systematic literature search identified eligible RCTs, which were combined with trials on aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone from a previous meta-analysis...In conclusion, selected second and TGAs, including M1/M4 receptor agonists such as xanomeline, may offer promising treatment options for cognitive dysfunction. Further research should personalize pharmacological strategies based on cognitive profiles."

Journal • Retrospective data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Valbenazine for the Treatment of Chronic Motor or Vocal Tic Disorder (CMVTD). (PubMed, Cureus) - "The present report describes a pediatric patient with CMVTD who had previously failed multiple pharmacological treatments, including two Food and Drug Administration (FDA)-approved agents (pimozide, aripiprazole), guanfacine, psychotherapy, and novel compounds (lumateperone, cariprazine). This case illustrates a marked therapeutic response to valbenazine in a patient with CMVTD refractory to conventional and novel therapies. These observations highlight the potential role of vesicular monoamine transporter 2 (VMAT2) inhibition in tic disorders and also the need for further clinical study."

Journal • CNS Disorders • Otorhinolaryngology • Pediatrics • Psychiatry • Tic Disorders • Tourette Syndrome

Role of PI3K/Akt axis in cognitive impact of lumateperone in schizophrenia rat model induced by ketamine. (PubMed, Int Immunopharmacol) - "WM pre-administration nullified LUM's effects, proving the involvement of the 5-HT1A/PI3K/Akt pathway. LUM demonstrates promising procognitive potential, offering insights into its therapeutic applications for cognitive dysfunction in SCZ."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia • BDNF • CD163 • CD86 • GFAP • SLC2A1

Lumateperone for the prevention of relapse in patients with schizophrenia: results from a double-blind, placebo-controlled, randomized withdrawal, phase 3 trial (ECNP 2025) - P3 | "Of 592 patients treated with lumateperone 42 mg in the open-label run-in phase, 228 patients meeting stabilization criteria were randomized to double-blind treatment (lumateperone, n=114; placebo, n=114). Of patients in the double-blind treatment phase, 130 (58%) completed double-blind treatment without relapse. Lumateperone met the primary endpoint, significantly delaying the time to relapse vs placebo during double-blind treatment (hazard ratio, 0.37; 95% CI, 0.22-0.65; P=.0002)."

Clinical • P3 data • Bipolar Disorder • CNS Disorders • Depression • Psychiatry • Schizophrenia

The influence of novel third-generation antipsychotic drug lumateperone on cytochrome P450 (CYP) enzymes in the liver. (ECNP 2025) - "Lumateperone affects the regulation of expression and activity of CYP-drug metabolizing enzymes at a molecular and functional level, which may lead to drug-drug metabolic interactions of pharmacological importance during long-term therapy with this antipsychotic. Since lumateperone is metabolized by CYP3A enzymes, it is also possible that this drug may inhibit its own metabolism, so that the plasma concentration of lumateperone in patients after prolonged treatment may be higher than expected after a single dose. On the other hand, this antipsychotic is not toxic to human hepatocytes after long-term treatment."

Bipolar Disorder • CNS Disorders • Depression • Psychiatry • Schizophrenia • CYP1A2 • CYP3A4 • DRD2

Evaluation of sexual function with adjunctive lumateperone in patients with major depressive disorder (ECNP 2025) - P3 | "Lumateperone 42 mg/day adjunctive to ADT was not associated with treatment-related sexual dysfunction and significantly improved sexual function compared with placebo adjunctive to ADT in patients with MDD with inadequate response to ADT."

Clinical • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Schizophrenia

A network meta-analysis of the efficacy, safety, and tolerability of xanomeline and trospium chloride versus eight atypical antipsychotics in schizophrenia (ECNP 2025) - P2, P3 | "Xanomeline/trospium treatment significantly improved odds of clinical response versus aripiprazole (odds ratio [OR]: 1.85; 95% credible interval [CrI]: 1.11, 3.11), brexpiprazole (OR: 2.23; 95% CrI: 1.34, 3.83), and cariprazine (OR: 2.05; 95% CrI: 1.19, 3.57), increased odds of all-cause discontinuation versus all comparators except cariprazine, and reduced odds of clinically significant weight gain versus aripiprazole, brexpiprazole, cariprazine, lumateperone, olanzapine, quetiapine, and risperidone. Additional favorable results for xanomeline/trospium included improvements in CFB CGI-S versus aripiprazole, brexpiprazole, cariprazine, and olanzapine, CFB PANSS positive symptoms score versus brexpiprazole, and CFB weight versus brexpiprazole, clozapine, olanzapine, quetiapine, and risperidone... The SLR identified 3664 unique references. After initial screening followed by the addition of 114 records identified from other sources, a total of 142 records from 111..."

Retrospective data • CNS Disorders • Psychiatry • Schizophrenia • DRD2

Efficacy of adjunctive lumateperone 42 mg treatment across depression and anhedonia symptoms in major depressive disorder (ECNP 2025) - P3 | "Adjunctive lumateperone 42 mg to ADT demonstrated efficacy, significantly improving a broad range of depression symptoms, including anhedonia, compared with adjunctive placebo in patients with MDD with inadequate response to ADT."

Clinical • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Schizophrenia • Suicidal Ideation

Long-term adjunctive lumateperone treatment in major depressive disorder: results from a six-month open-label extension study (ECNP 2025) - P3 | "Lumateperone 42 mg adjunctive to ADT was safe and effective during 26-week treatment in patients with MDD and inadequate ADT response, supporting long-term adjunctive lumateperone 42 mg treatment in this population."

Clinical • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Schizophrenia • Suicidal Ideation

When aggression escalates: intermittent explosive disorder in an adolescent with autism spectrum disorder (ECNP 2025) - "In cases involving overlapping ASD and IED, a combination of behavioral therapy and pharmacological interventions — including second-generation antipsychotics (e.g., olanzapine, quetiapine, ziprasidone), GABAergic agents (amantadine, baclofen) — has been recommended to reduce episodic aggression [4]...The observed reduction in episodic aggression with a combination of aripiprazole and short-term olanzapine supports the potential utility of tailored antipsychotic regimens...Lumateperone: a novel agent for aggression. CNS Drugs. No conflict of interest"

Behavior Disorders • CNS Disorders • Mental Retardation • Psychiatry

Adjunctive lumateperone 42 mg treatment in major depressive disorder: efficacy in anhedonia and across broad range of depressive symptoms (ECNP 2025) - P3 | "Lumateperone 42 mg adjunctive to ADT significantly improved symptoms of anhedonia and a broad range of depression symptoms compared with placebo adjunctive to ADT in patients with MDD with inadequate response."

Clinical • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Schizophrenia

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

ADJUNCTIVE LUMATEPERONE IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER AND ANXIOUS DISTRESS (WPA-WCP 2025) - P3 | "Conclusions Adjunctive lumateperone 42mg improved depression symptoms compared with adjunctive placebo according to both clinician-rated and patient-reported outcomes. These results support lumateperone 42mg as a promising adjunctive therapy in patients with MDD who have inadequate ADT response and anxious distress."

Clinical • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Schizophrenia

ADJUNCTIVE LUMATEPERONE 42 MG IN THE TREATMENT OF MAJOR DEPRESSIVE DISORDER: A POOLED ANALYSIS OF 2 PHASE 3 RANDOMIZED CONTROLLED TRIALS (WPA-WCP 2025) - P3 | "With lumateperone+ADT there were no clinically relevant increases at the end of treatment in body morphology, prolactin, cardiometabolic parameters, or extrapyramidal symptom scales. Conclusions In this pooled analysis, lumateperone 42mg+ADT was generally safe and well tolerated with robust, clinically-meaningful efficacy over placebo+ADT in adults with MDD with inadequate ADT response."

P3 data • Retrospective data • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Schizophrenia

Efficacy of Lumateperone in Depression Associated With Bipolar II Disorder: A Pooled Analysis of Late-Phase Clinical Trials. (PubMed, CNS Spectr) - No abstract available

Journal • Retrospective data • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

Response and Remission Outcomes of Lumateperone for Major Depressive Episodes With Mixed Features in Major Depressive Disorder and Bipolar I or Bipolar II Disorder (ISBD 2025) - P3 | "Lumateperone 42mg demonstrated efficacy in improving both depressive and manic symptoms, measured by composite response and remission, in patients with depressive episodes with mixed features associated with MDD or bipolar disorder. Novelty/Unique Data This post hoc analysis of the first prospective study of lumateperone to treat DSM-5 –diagnosed major depressive disorder (MDD) or bipolar depression with mixed features measured composite response and remission. This novel analysis assessed concurrent improvement in both depression (Montgomery-Asberg Depression Rating Scale [MADRS]) and mania (Young Mania Rating Scale [YMRS]) symptoms."

Clinical • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Schizophrenia

Lumateperone Treatment for Major Depressive Episodes With Mixed Features in Major Depressive Disorder and Bipolar I or Bipolar II Disorder: Post Hoc Analysis of Anhedonia (ISBD 2025) - P3 | "Lumateperone 42mg improved a range of anhedonia symptoms and was generally well-tolerated in patients with MDD or bipolar depression with mixed features. Novelty/Unique Data This analysis investigated the effect of lumateperone 42 mg on symptoms of anhedonia in the first prospective study of lumateperone to treat DSM-5 –diagnosed major depressive disorder (MDD) with mixed features or bipolar depression with mixed features. The results, which have not yet been published in manuscript form as the draft is in preparation, indicate that lumateperone significantly improved the Montgomery-Asberg Depression Rating Scale (MADRS) anhedonia factor score and its individual MADRS Item components related to anhedonia, compared with placebo, in patients with MDD or bipolar depression with mixed features."

Retrospective data • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Schizophrenia