Lybalvi (olanzapine/samidorphan) / Alkermes - LARVOL DELTA

Safety profile of olanzapine/samidorphan: focus on metabolic risks, opioid-related effects, and novel adverse events identified. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Psychiatric disorders, notably suicidal ideation, require vigilant monitoring in clinical settings. It is imperative to conduct traditional pharmacoepidemiological research to evaluate risk factors of O/S-related metabolic diseases in the future."

Adverse events • Journal • Bipolar Disorder • CNS Disorders • Diabetes • Mental Retardation • Metabolic Disorders • Psychiatry • Schizophrenia • Suicidal Ideation

Olanzapine/Samidorphan (Lybalvi) in Palliative Care: A Case Report on Medication Reconciliation, Risk-Benefit Analysis, and Psychiatric Co-Management in an Outpatient Supportive Oncology Clinic. (PubMed, J Palliat Med) - "Notably, patients with comorbid bipolar I disorder and cancer often have both significant anorexia and pain, making samidorphan less desirable, as, in addition to mitigating metabolic side effects, it can limit the efficacy of analgesia from opioids. A recommendation of transitioning to olanzapine only is discussed."

Benefit-risk assessment • Journal • Anorexia • Bipolar Disorder • CNS Disorders • Mental Retardation • Oncology • Pain • Palliative care • Psychiatry

Successful Treatment of Antipsychotic-Induced Hyperphagia With Intramuscular Naltrexone (OBESITY WEEK 2025) - " A 37-year-old gentleman presented to the primary care clinic to establish care 6 months after initiation of intramuscular haloperidol and paliperidone every 21 days for management of his severe disorganized schizophrenia...Due to the severity of his mental illness, patient was not a candidate for transition to oral samidorphan-olanzapine or addition of oral naltrexone-buproprion therapy... Treatment options for individuals with antipsychotic-associated hyperphagia who have severe mental illness and are intolerant to oral medications are currently limited, putting them at risk for the long-term health effects associated with antipsychotic-induced weight gain. This case study indicates that patients in this unique and challenging situation may benefit from injectable anti-opiate therapy such as naltrexone. Future research is needed to determine the viability and long-term effects of injectable anti-opiate therapy in this population."

Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry • Schizophrenia

Molecular determinants of the different metabolic adverse effects of antipsychotics (ECNP 2025) - "The olanzapine-samidorphan combination is presently the sole instance of co-treatment aimed at mitigating weight gain; nonetheless, the product information indicates that fasting triglycerides are elevated with olanzapine, even when samidorphan is administered concurrently.This example underscores that the processes underlying the unfavorable metabolic effects of antipsychotics are poorly understood, a knowledge gap we aim to address...Their primary targets are the enzymes that synthesize cholesterol, the lysosomal apparatus that processes endocited cholesterol, and the resulting modifications to gene transcription and metabolic control, which involve SREBPs, AMPK, and more.We have identified significant variations in the metabolic adverse action of three antipsychotics—olanzapine (high risk), risperidone (mid risk), and ziprasidone (low risk)—that may account for their varying effects on patients...While studying these antipsychotics, we found that co-treatment with..."

Adverse events • CNS Disorders

New Developments in the Treatments of Psychosis (WFSBP 2025) - "Objective: Despite the discovery of chlorpromazine over 70 years ago and substantial pharmacologic advances, postsynaptic dopamine blockade has remained the sole mechanism of action of approved drugs for schizophrenia... Newly/recently approved agents include vesicular monoamine transporter-2 inhibitors valbenazine and deutetrabenazine for tardive dyskinesia and, possibly, residual positive symptoms; olanzapine/samidorphan combination, lumateperone, new formulations, including subcutaneous injections, and ultra-long-acting injectable antipsychotics. Agents in development that have at least one positive phase 1B, 2 or 3 trial include the trace amine-associated receptor-1 (TAAR1) ulotaront, M1/M4 muscarinic agonist xanomeline plus peripherally restricted anticholinergic trospium, the M4 muscarinic positive allosteric modulator emraclidine, as well as multiple other muscarinic receptor modulators for total psychopathology, methylated amisulpride (LB-102), and evenamide, a..."

CNS Disorders • Movement Disorders • Psychiatry • Schizophrenia

Contrave, Lybalvi, Auvelity, and Cobenfy: What Do They Have in Common? (PubMed, J Psychiatr Pract) - "This column reviews 4 psychiatric combination products: Contrave (bupropion + naltrexone), Lybalvi (olanzapine + samidorphan), Auvelity (dextromethorphan + bupropion), and Cobenfy (xanomeline + trospium). In each case, the second drug in the combination enhances the efficacy and/or reduces the adverse effects of the first drug. This review illustrates how basic science in pharmacokinetics and brain circuitry was fundamental to the development of these products, particularly in the case of Contrave and Cobenfy."

Journal • Review • Psychiatry

Olanzapine/Samidorphan (Lybalvi) and Buprenorphine: Considerations for a Contradictory Combination: A Case Report. (PubMed, J Addict Med) - "This case report outlines the safety concerns of utilizing an opioid antagonist (samidorphan) in conjunction with an opioid partial agonist (buprenorphine) and demonstrates the process for safe transition to an alternative regimen."

Journal • Addiction (Opioid and Alcohol) • Bipolar Disorder • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • Schizophrenia • Substance Abuse

Healthcare Resource Utilization 6 Months Before and After Olanzapine/Samidorphan Initiation: Real-World Assessment of Patients with Schizophrenia or Bipolar I Disorder. (PubMed, Adv Ther) - "Results from this first real-world study assessing HCRU after OLZ/SAM initiation suggest that OLZ/SAM results in reductions in burden for patients, providers, and the healthcare system, as evidenced by reductions in acute all-cause, MH-related, and disease-specific HCRU among SZ and BD-I cohorts."

HEOR • Journal • Real-world evidence • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia

Exercise and Olanzapine-samidorphan (clinicaltrials.gov) - P4 | N=30 | Recruiting | Sponsor: New York State Psychiatric Institute | Not yet recruiting ➔ Recruiting

Enrollment open • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry • Schizophrenia

New Agents in the Treatment of Psychiatric Disorders: What Innovations and in What Areas of Psychopathology? (PubMed, Pharmaceuticals (Basel)) - "Our search suggested that a new antipsychotic, lumateperone, and two drug combinations, olanzapine/samidorphan (OLZ/SAM) and xanomeline/trospium (KarXT), were approved for schizophrenia...Two new agents, brexanolone and zuranolone, were approved for treatment of postpartum depression...In summary, some new psychotropic medications have been developed, in particular with the aim to improve the symptoms of resistant patients and to decrease the incidence of adverse effects. It is necessary to continue testing the effectiveness of new compounds in methodologically rigorous studies."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Obsessive-Compulsive Disorder • Postpartum Depression • Psychiatry • Schizophrenia • Suicidal Ideation

Centrally-acting opioid receptor antagonists as a treatment for antipsychotic-induced weight gain: A systematic review and meta-analysis of clinical trial data. (PubMed, J Psychopharmacol) - "CORA, specifically samidorphan, was effective at reducing weight gain in individuals prescribed olanzapine. The small effect sizes and discrepancy between samidorphan and naltrexone suggest effects may be timing dependent, not a class effect, or dependent on the antipsychotic combination."

Journal • Retrospective data • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry • Schizophrenia

Healthcare Resource Utilization 12 Months Following Initiation of Olanzapine/Samidorphan: Real-World Assessment of Patients With Bipolar I Disorder (ISPOR 2025) - "Among patients with BD-I, OLZ/SAM initiation results in clinically meaningful reductions in disease burden, as evidenced by reductions in hospital-based HCRU. Longer OLZ/SAM treatment retention was associated with improved effectiveness. This study was sponsored by Alkermes, Inc."

Clinical • HEOR • Real-world • Real-world evidence • Bipolar Disorder • CNS Disorders • Psychiatry

Healthcare Resource Utilization 12 Months Following Initiation of Olanzapine/Samidorphan: Real-World Assessment of Patients With Schizophrenia (ISPOR 2025) - "Among patients with schizophrenia, OLZ/SAM initiation may result in clinically meaningful reductions in real-world disease burden, as evidenced by reductions in hospital-based HCRU. Longer treatment retention was associated with improved effectiveness. This study was sponsored by Alkermes, Inc."

Clinical • HEOR • Real-world • Real-world evidence • CNS Disorders • Psychiatry • Schizophrenia

A pharmacovigilance study of olanzapine/samidorphan based on FDA Adverse Event Reporting System (FAERS). (PubMed, BMC Pharmacol Toxicol) - "The long-term safety of the OLZ/SAM warrants attention, particularly concerning drug withdrawal syndrome."

Adverse events • Journal • Addiction (Opioid and Alcohol) • CNS Disorders

Alkermes plc Reports Financial Results for the Fourth Quarter and Year Ended Dec. 31, 2024 and Provides Financial Expectations for 2025 (PRNewswire) - "'This year, we have clear objectives for our pipeline as we complete the phase 2 studies for ALKS 2680 in narcolepsy, with data expected in the second half of the year, and prepare to initiate the ALKS 2680 phase 2 study in idiopathic hypersomnia...LYBALVI: Revenues for the fourth quarter were $77.0 million. Fourth quarter revenues and total prescriptions grew 37% and 30%, respectively, compared to the fourth quarter of 2023...ARISTADA: Revenues for the fourth quarter were $96.6 million. Fourth quarter revenues grew 16% compared to the fourth quarter of 2023...VIVITROL: Revenues for the fourth quarter were $134.1 million. Fourth quarter revenues grew 31% compared to the fourth quarter of 2023."

Commercial • New P2 trial • P2 data • Bipolar Disorder • CNS Disorders • Narcolepsy • Schizophrenia • Sleep Disorder

Olanzapine/Samidorphan Effects on Weight Gain: An Individual Patient Data Meta-Analysis of Phase 2 and 3 Randomized Double-Blind Studies. (PubMed, J Clin Psychiatry) - "Fewer patients treated with OLZ/SAM gained ≥7% (23.9% vs 34.6%; odds ratio [OR] = 0.58; 95% CI, 0.043-0.79) or ≥10% (13.7% vs 20.4%; OR = 0.60; 95% CI, 0.42-0.88) of their baseline body weight at week 12. In this IPD meta-analysis, OLZ/SAM treatment was associated with less weight gain and reduced risk of reaching ≥7% or ≥10% gain in body weight versus olanzapine over 12 weeks."

Clinical • Journal • P2 data • Retrospective data • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia

Exercise and Olanzapine-samidorphan (clinicaltrials.gov) - P4 | N=30 | Not yet recruiting | Sponsor: New York State Psychiatric Institute

New P4 trial • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry • Schizophrenia

Long-Term Safety, Tolerability, and Durability of Treatment Effect of Olanzapine and Samidorphan: Results of a 4-Year Open-Label Study. (PubMed, J Clin Psychiatry) - P3 | " OLZ/SAM maintained symptom control with a long-term safety profile over 4 years consistent with that of prior studies. Trials Registration: ClinicalTrials.gov identifier: NCT03201757."

Journal • Bipolar Disorder • CNS Disorders • Insomnia • Mood Disorders • Pain • Psychiatry • Schizophrenia • Schizophreniform Disorder • Sleep Disorder

Olanzapine and Samidorphan in Pediatric Patients With Bipolar I Disorder: Pharmacokinetic Results From a Phase 1, Multidose, Open-Label Study (AACAP 2024) - P1 | "In pediatric patients with stable BD-I, OLZ/SAM was generally well tolerated, consistent with findings in adults. Olanzapine exposure increased dose-proportionally and was higher in pediatric patients than it was observed in adults, likely due to body weight differences. Samidorphan exposure was comparable with that in adults.BRD, PKS, APS"

Clinical • P1 data • PK/PD data • Bipolar Disorder • CNS Disorders • Depression • Fatigue • Mood Disorders • Pain • Pediatrics • Psychiatry • Schizophrenia

A Phase III Clinical Study to Evaluate the Safety and Efficacy of Olanzapine-Samidorphan Tablets in Adults With Schizophrenia (clinicaltrials.gov) - P3 | N=654 | Not yet recruiting | Sponsor: Qilu Pharmaceutical Co., Ltd.

New P3 trial • 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

Long-Term Safety and Efficacy of Olanzapine/Samidorphan: Results of a 4-Year Open-Label Study (ASCP 2024) - P3 | "Of 524 patients enrolled in the study, 523 received ≥1 dose of OLZ/SAM. 188 (35.9%) patients completed between 2 to 4 years of treatment. The mean (SD) duration of exposure was 652.4 (454.8) days."

Clinical • Bipolar Disorder • CNS Disorders • Insomnia • Mood Disorders • Pain • Psychiatry • Schizophrenia • Schizophreniform Disorder • Sleep Disorder

Long-term Safety and Efficacy of Olanzapine/Samidorphan: Results of a 4-Year Open-Label Study (APA 2024) - P3 | "In this 4-year open-label extension study, treatment with OLZ/SAM resulted in a safety profile consistent with previous short-term studies and was associated with minimal changes in body weight, waist circumference, and lipid and glycemic parameters. Similarly, OLZ/SAM maintained symptom control during long-term treatment. Based on these results, OLZ/SAM maintained long-term antipsychotic efficacy while mitigating the weight gain and metabolic dysfunction associated with olanzapine."

Clinical • Bipolar Disorder • CNS Disorders • Dyslipidemia • Insomnia • Metabolic Disorders • Mood Disorders • Pain • Psychiatry • Schizophrenia • Schizophreniform Disorder • Sleep Disorder

Healthcare Resource Utilization Following 6 Months of Treatment With Olanzapine/Samidorphan: Real-World Assessment of Patients With Schizophrenia or Bipolar I Disorder (ISPOR 2024) - "Among patients with SZ or BD-I, real-world OLZ/SAM initiation was associated with significant reductions in proportions of patients with all-cause and mental health–related hospitalizations and ED visits, indicating that OLZ/SAM may result in clinically meaningful reductions in disease burden, as evidenced by changes in inpatient care."

Clinical • HEOR • Real-world • Real-world evidence • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia

Treating Schizophrenia and Bipolar I Disorder in the Real-World Setting: Effectiveness and Safety of Olanzapine/Samidorphan Combination. (PubMed, Prim Care Companion CNS Disord) - No abstract available

Journal • Real-world • Real-world evidence • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia