samidorphan (ALKS 33) / Alkermes - LARVOL DELTA

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

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

Iloperidone (Fanapt) - a new indication for bipolar disorder. (PubMed, Med Lett Drugs Ther) - No abstract available

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

New Development of Antipsychotic Drugs in Schizophrenia (NDS 2024) - "Among these newer antipsychotic drugs are cariprazine, brexipiprazole and lumateperone, which exert a partial agonistic effect at D2 and 5-HT2A receptors, pimvanserin a 5-HT2A receptor antagonist which treats negative schizophrenic symptoms as an add-on therapy, olanzapine combined with samidorphan, which reduces weight gain, and M4 or M1 receptor agonists, for example xanomeline with an antipsychotic effect combined with tropsium, an anticholinergic drug...Pimavanserin reduces negative schizophrenic symptoms as an additional pharmacotherapy in schizophrenia...The long-term efficacy should still be examined. Newer antipsychotic drugs are for example xanomeline, a M4 or M1 receptor agonist, which has been combined with tropsium, an anticholinergic drug, the mechanism of action of which can be derived from the neural network suggested in this review."

CNS Disorders • Psychiatry • Schizophrenia

Drugs for bipolar disorder. (PubMed, Med Lett Drugs Ther) - No abstract available

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

Insulin Resistance/Diabetes and Schizophrenia: Potential Shared Genetic Factors and Implications for Better Management of Patients with Schizophrenia. (PubMed, CNS Drugs) - "The present findings and observations may have clinical implications for the development of better strategies to treat patients with schizophrenia, with both pharmacological (i.e., samidorphan, empagliflozin) and/or nonpharmacological (i.e., lifestyle changes) approaches. Additionally, this review may benefit the design of future studies by physicians and clinical investigators."

Journal • Review • CNS Disorders • Cognitive Disorders • Diabetes • Metabolic Disorders • Psychiatry • Schizophrenia • Type 2 Diabetes Mellitus

Olanzapine/Samidorphan Effects on Weight Gain: A Pooled Analysis of Phase 2 and 3 Randomized, Double-Blind Studies (ACNP 2023) - P2, P3 | "In this pooled post hoc analysis, treatment with OLZ/SAM was consistently associated with less weight gain and reduced odds of ≥7% or ≥10% weight gain at week 12 versus olanzapine."

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

Effects of Combined Therapy of Olanzapine and Samidorphan on Safety and Metabolic Parameters in Schizophrenia Patients: A Meta-Analysis. (PubMed, Neuropsychiatr Dis Treat) - "These findings provide clinicians with evidence-based guidance and support for drug selection. However, it is crucial to confirm these findings through further high-quality research."

Journal • Retrospective data • CNS Disorders • Dyslipidemia • Pain • Psychiatry • Schizophrenia • Xerostomia

Economic Impact of Discontinuation and Relapse Rates Among Patients with Schizophrenia Newly Initiated on Lybalvi Versus Olanzapine during First Year Use (ISPOR 2023) - "During 2021, the US Food and Drug Administration approved a combination of OLZ and samidorphan (OLZ/SAM [LYBALVI®]) for the treatment of adults diagnosed with schizophrenia or bipolar I disorder. In this analysis, OLZ/SAM has 50% lower relapse rates during 1 year versus OLZ, and OLZ/SAM demonstrated a 60% cost-savings versus OLZ. OLZ/SAM could be considered as first line therapy due to better adherence measures."

Clinical • HEOR • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia

In vivo Characterization of the Opioid Receptor-Binding Profiles of Samidorphan and Naltrexone in Rats: Comparisons at Clinically Relevant Concentrations. (PubMed, Neuropsychiatr Dis Treat) - "The atypical antipsychotic olanzapine is approved for the treatment of schizophrenia and bipolar I disorder; however, weight gain and metabolic dysregulation associated with olanzapine therapy have limited its clinical utility...At clinically relevant concentrations, samidorphan occupied MOR, DOR, and KOR, whereas naltrexone occupied only MOR and KOR. The binding profile of samidorphan differs from that of naltrexone, with potential clinical implications."

Journal • Preclinical • Addiction (Opioid and Alcohol) • Bipolar Disorder • CNS Disorders • Metabolic Disorders • Psychiatry • Schizophrenia

Reduction in Multiple Cardiometabolic Risk Factors With Combined Olanzapine/Samidorphan Compared With Olanzapine: Post Hoc Analyses From a 24-Week Phase 3 Study. (PubMed, Schizophr Bull) - P3 | "OLZ/SAM treatment was associated with lower risk of worsening cardiometabolic risk factors related to obesity, hypertension, and metabolic syndrome relative to olanzapine. NCT02694328, https://clinicaltrials.gov/ct2/show/NCT02694328."

Journal • P3 data • Retrospective data • Cardiovascular • CNS Disorders • Diabetes • Dyslipidemia • Genetic Disorders • Hypertension • Metabolic Disorders • Obesity • Psychiatry • Schizophrenia

Off-label and investigational drugs in the treatment of alcohol use disorder: A critical review. (PubMed, Front Pharmacol) - "Compounds known to be successful in the treatment of alcohol use disorder include the aversive agent, Disulfiram, the glutamatergic NMDA receptor antagonist, Acamprosate, and the opioid receptor antagonists, Naltrexone and Nalmefene...In this review we summarize and compare Baclofen, Gabapentin, Topiramate, Ondansetron, Varenicline, Aripiprazole, Quetiapine, Clozapine, Antidepressants, Lithium, Neuropeptide Y, Neuropeptide S, Corticotropin-releasing factor antagonists, Oxytocin, PF-05190457, Memantine, Ifenprodil, Samidorphan, Ondelopran, ABT-436, SSR149415, Mifepristone, Ibudilast, Citicoline, Rimonabant, Surinabant, AM4113 and Gamma-hydroxybutyrate While some have shown promising results in the treatment of alcohol use disorder, others have disappointed and should be excluded from further investigation. Here we discuss the most promising results and highlight medications that deserve further preclinical or clinical study. Effective, patient-tailored treatment will..."

Journal • Review • Addiction (Opioid and Alcohol)

Olanzapine/samidorphan combination consistently mitigates weight gain across various subgroups of patients. (PubMed, CNS Spectr) - P3 | "In these exploratory subgroup analyses from the ENLIGHTEN-2 study, weight-mitigating effects of OLZ/SAM vs olanzapine were observed consistently across patient subgroups and were in line with results from the overall study population."

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

Pharmacological interventions for prevention of weight gain in people with schizophrenia. (PubMed, Cochrane Database Syst Rev) - "There is low-certainty evidence to suggest that metformin may be effective in preventing weight gain. Interpretation of this result and those for other agents, is limited by the small number of studies, small sample size, and short study duration. In future, we need studies that are adequately powered and with longer treatment durations to further evaluate the efficacy and safety of interventions for managing weight gain."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

Opioid antagonists to prevent olanzapine-induced weight gain: A systematic review. (PubMed, Ment Health Clin) - "Six studies met inclusion criteria, 5 of which assessed OLZ and samidorphan (SAM) and 1 of which assessed OLZ and naltrexone compared with OLZ monotherapy...Naltrexone did not reduce OLZ-induced increases in weight or BMI. However, there is a paucity of data on other opioid antagonists as adjuncts to OLZ treatment to prevent increases in weight or BMI."

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

Samidorphan for the treatment of weight gain associated with olanzapine in patients with schizophrenia and bipolar disorder. (PubMed, Expert Rev Clin Pharmacol) - "OLZ/SAM was well tolerated. Therefore, it is a potential new treatment option for schizophrenia."

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

Samidorphan/olanzapine combination therapy for schizophrenia: Efficacy, tolerance and adverse outcomes of regimen, evidence-based review of clinical trials. (PubMed, Ann Med Surg (Lond)) - "The FDA-approved drug recombination of OLZ/SAM for the treatment of schizophrenia revealed efficacious outcomes and was generally well tolerated by patients partaking in various trials. The potential of samidorphan in mimicking the efficacy of olanzapine while mitigating olanzapine-induced weight gain makes it a promising regimen for improving symptoms and health outcomes in schizophrenic patients."

Adverse events • Combination therapy • Journal • Review • Bipolar Disorder • CNS Disorders • Diabetes • Metabolic Disorders • Movement Disorders • Psychiatry • Schizophrenia

Semaglutide for the Treatment of Weight Gain Associated with Antipsychotics in Patients with Schizophrenia: Proposed Design for a Randomized Controlled Trial - "Metformin, topiramate, lorcaserin, orlistat, naltrexone, and samidorphan are among the most studied medications to prevent or reverse the weight gain associated with antipsychotics, which have shown to mildly attenuate the weight gain effect of antipsychotics and result in two-to-five-kilogram weight reduction compared to placebo...Using semaglutide as an adjunctive agent to antipsychotics in patients with schizophrenia can potentially attenuate the weight gain caused by antipsychotics and may cause significant further weight reduction. Accreditation Post-Test Question Post-Test Question Semaglutide is approved by FDA for the treatment of:"

Clinical • CNS Disorders • Psychiatry • Schizophrenia • Schizophreniform Disorder

Olanzapine/samidorphan (Lybalvi) for schizophrenia and bipolar disorder. (PubMed, Med Lett Drugs Ther) - No abstract available

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

UofL SOM Psychiatry Journal Club 9 9 2021 Crump (YouTube) - "Dr...discusses: 'Effects of Olanzapine Combined With Samidorphan on Weight Gain in Schizophrenia: A 24-Week Phase 3 Study.' Christoph U. Correll, M.D..."

Video • Schizophrenia

[VIRTUAL] Evidence-based therapeutic management of binge-eating disorder (EPA 2021) - "Lisdexamfetamine dimesylate is the only FDA approved drug for this indication, as dasotraline was rejected by FDA and its research discontinued by the manufacturer. Fluoxetine, sertraline, escitalopram, duloxetine, bupropion, atomoxetine, reboxetine, armodafinil, disulfiram, baclofen, zonisamide, lamotrigine, topiramate, samidorphan, liraglutid, and orlistat need more trials in order to validate their efficacy, especially on long term.  Conclusions There is only one drug currently FDA approved for this indication, lisdexamfetamine, and a number of psychotherapies, with CBT and IPT being the most supported by evidence."

Binge Eating Disorder • CNS Disorders • Mood Disorders • Psychiatry

[VIRTUAL] Long-term safety of olanzapine and samidorphan combination in patients with schizophrenia: pooled analyses from phase 2 and 3 studies (AMCP 2021) - "OLZ/SAM was well tolerated in adults with SZ for up to 3 years of treatment."

Clinical • P2 data • Bipolar Disorder • CNS Disorders • Pain • Psychiatry • Schizophrenia • Xerostomia

[VIRTUAL] In Vivo Characterization of the Opioid Receptor Binding Profiles of Samidorphan and Naltrexone in Rats: Comparisons at Clinically Relevant Concentrations (ASCP 2021) - "Background : A combination of olanzapine and the opioid receptor antagonist samidorphan (OLZ/SAM) is under development for the treatment of schizophrenia and bipolar I disorder. Based on these data, samidorphan has a differentiated binding profile from naltrexone. Learning Objectives 1. Describe the binding profile of samidorphan at μ-, κ-, and δ-opioid receptors 2."

Preclinical • Bipolar Disorder • CNS Disorders • Psychiatry • Schizophrenia

[VIRTUAL] Population Pharmacokinetic-Pharmacodynamic Analysis to Explore the Concentration-Response Relationship in Patients with Schizophrenia Treated with Olanzapine Alone or in Combination with Samidorphan (ASCP 2021) - "The antipsychotic efficacy of olanzapine was not affected by the addition of samidorphan at any concentration of olanzapine. Furthermore, olanzapine-associated weight gain did not correlate with olanzapine dose or plasma concentration. Lastly, the effect of OLZ/SAM on mitigation of olanzapine-associated weight gain was not affected by inter-subject variability in olanzapine and/or samidorphan plasma concentrations."

Clinical • Combination therapy • PK/PD data • CNS Disorders • Psychiatry • Schizophrenia

[VIRTUAL] Opioid Antagonism as a Target for Mitigation of Antipsychotic-Associated Weight Gain (ASCP 2021) - "Opioid receptor blockade from samidorphan (in OLZ/SAM) mitigated olanzapine-associated weight gain and may provide additional benefits on other metabolic sequelae. Nonclinical and human data suggest that antagonism of the endogenous opioid system is a potential mechanism to address antipsychotic-associated weight gain and metabolic dysregulation. Learning Objectives 1."

CNS Disorders • Psychiatry • Schizophrenia