Olanzapine/Samidorphan Tied to Longer Persistence in Schizophrenia

Patients with schizophrenia who initiated olanzapine/samidorphan (OLZ/SAM) were more likely to stay on treatment than patients who started other oral second-generation antipsychotics, and the combination also led to superior treatment adherence and reduced hospitalizations compared with olanzapine alone in schizophrenia and bipolar I disorder, according to claims analyses presented at the Academy of Managed Care Pharmacy Nexus 2026 meeting. This research incorporated data from the Komodo Healthcare Map database.

Why Does Staying on Treatment Matter?

Stopping an antipsychotic is a well-known problem in schizophrenia.^1-3 Study authors note that “poor persistence and adherence to oral antipsychotic medications are common in clinical practice and are associated with increased relapse risk [and that] treatment continuity may indicate that a medication has an acceptable balance of symptom relief and tolerability over time for a given individual.”⁴

For these analyses, the investigators defined persistence as a patient staying on the same medication they started on the index date, as indicated by pharmacy claims, and they based adherence on the days’ supply of the medication patients were dispensed on the index date.^4-5 Discontinuation was defined as a minimum 45-day gap in therapy with the index medication. Both also required at least 12 months of continuous medical and pharmacy enrollment before and after the index date or the day a patient started the study medication.

Longer Persistence Than Oral Comparators⁴

The first analysis comprised 45,566 adults with schizophrenia who filled a prescription for OLZ/SAM (n = 1244) or a comparator medication between October 2020 and December 2024. The comparator medications were aripiprazole, cariprazine, lurasidone, olanzapine, and risperidone. The cohorts were balanced on demographic and clinical variables. Approximately 47% of the patients in each group were female patients, and close to two-thirds were aged 25 to 44 years. Only 1% were 65 years or older. The follow-up period was 12 months.

Patients who started OLZ/SAM “were significantly more likely to remain on treatment at 12 months,” with ORs of 1.57 to 2.71 (P < .001). Mean (SD) treatment persistence was 201.8 (143.6) days with OLZ/SAM compared with 132.1 to 174.1 for the comparators:

• Aripiprazole: 132.1 (129.5) days
• Lurasidone: 160.6 (132.5) days
• Olanzapine: 151.0 (141.4) days
• Risperidone: 147.9 (138.0) days
• Cariprazine: 174.1 (138.8) days

In addition, at least half of the patients on OLZ/SAM stayed on treatment for 280 days or longer vs median durations of 67 to 121 for the comparators. Adherence, defined as a medication possession ratio of 0.80 or higher, also favored OLZ/SAM, with ORs of 1.33 to 2.53 (all P < .01). The degree of the advantage varied by comparator drug, and the gap was more narrow against some drugs compared with others, the authors highlighted, so the pooled picture should be read alongside the individual comparisons.

The authors concluded that “more consistent antipsychotic medication use may translate into meaningful improvements in schizophrenia-associated outcomes.”

Fewer Acute Care Events⁵

In the second poster, the authors sought to answer this question: Were there differences in treatment patterns and acute care events between use of OLZ/SAM and use of olanzapine alone? The study authors were unaware of previous real-world analysis of their question. For this investigation, Medicaid-insured adults were matched 1:1. For the schizophrenia analysis, there were 807 patients each on OLZ/SAM and olanzapine alone. For BD-1, 504 patients each, respectively.

For schizophrenia, 63.1% of patients receiving the combination were adherent compared with 45.0% of those receiving olanzapine alone (OR, 2.09; 95% CI, 1.72-2.54; P < .001). Mean (SD) persistence was 202.9 (144.3) vs 146.8 (140.0) days, respectively, and discontinuation was less common with OLZ/SAM (61.0% vs 75.8%; OR, 0.50; 95% CI, 0.40-0.61; P < .001). For BD-I, the results trended similarly, with an adherence rate of 57.5% with OLZ/SAM vs 48.2% with olanzapine (OR, 1.46; 95% CI, 1.14-1.86; P = .003), and discontinuation was lower (66.9% vs 79.2%; OR, 0.53; 95% CI, 0.40-0.71; P < .001). Time on treatment was also longer with OLZ/SAM: by 38% in schizophrenia and 29% in BD-I.

Hospital and emergency department (ED) use, which the authors treated as proxies for relapse, again favored OLZ/SAM. In schizophrenia, 31.9% of patients on OLZ/SAM had an all-cause inpatient admission vs 46.0% of patients on olanzapine alone (OR, 0.55; 95% CI, 0.45-0.67; P < .001), 28.1% vs 43.0% had a mental health–related admission (OR 0.52; 95% CI, 0.42-0.64; P < .001), and 24.2% vs 35.2% had a schizophrenia-related admission (OR 0.59; 95% CI, 0.47-0.73) (all P < .001). In BD-1, the respective findings were 25.2% vs 36.9% (OR, 0.58; 95% CI, 0.45-0.74), 21.2% vs 33.3% (OR, 0.54; 95% CI, 0.41-0.71), and 16.1% vs 27.0% (OR, 0.52; 95% CI, 0.38-0.70) (all P < .001).

ED visits were also less likely with OLZ/SAM in the schizophrenia arm, with an OR of 0.47 (95% CI, 0.38-0.57) for a mental health–related admission, 0.51 (95% CI, 0.41-0.64) for a disease-related admission, and 0.54 (95% CI, 0.44-0.66) for an all-cause admission (all P < .001). In BD-I, the respective ORs were 0.63 (95% CI, 0.48-0.82; P < .001), 0.62 (95% CI, 0.44-0.86; P = .004), and 0.74 (95% CI, 0.58-0.95; P = .019).

The authors concluded that a “significantly lower likelihood of disease-related acute care events suggests a lower relapse risk with OLZ/SAM treatment.”

References

1. Zipursky RB, Agid O, Remington G. Antipsychotic discontinuation in schizophrenia: rational or reckless? Schizophrenia (Heidelb). 2025;11(1):150. doi:10.1038/s41537-025-00698-8
2. Taylor D. Special feature on antipsychotic discontinuation in schizophrenia. Schizophrenia (Heidelb). 2025;11(1):152. doi:10.1038/s41537-025-00696-w
3. Read J. The experiences of 585 people when they tried to withdraw from antipsychotic drugs. Addict Behav Rep. 2022;15:100421. doi:10.1016/j.abrep.2022.100421
4. Cutler AJ, Correll CU, Jain R, et al. Real-world persistence on olanzapine/samidorphan versus other oral second-generation antipsychotics in patients with schizophrenia. Presented at: AMCP Nexus 2026; October 26-29, 2026; San Diego, CA. Poster 214.
5. Panchmatia HR, Jain R, Hughes AG, Doane MJ, Chepke C, Cutler AJ. Real-world comparison of olanzapine/samidorphan vs olanzapine: an assessment of treatment patterns and acute care events among patients with schizophrenia or bipolar I disorder. Presented at: AMCP Nexus 2026; October 26-29, 2026; San Diego, CA. Poster 213.