Real-World Data Show Patients With Schizophrenia Adhere Better to Clozapine and LAIs

Abstract

Back to table of contents Previous article Next article Clinical & ResearchFull AccessReal-World Data Show Patients With Schizophrenia Adhere Better to Clozapine and LAIsNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:8 Oct 2021https://doi.org/10.1176/appi.pn.2021.9.32AbstractAn analysis of national VA health databases shows clozapine along with long-acting formulas of aripiprazole and paliperidone have lower discontinuation rates than oral olanzapine, while oral quetiapine and ziprasidone have higher discontinuation rates.Patients with schizophrenia may be less likely to discontinue treatment if prescribed clozapine or long-acting injectable (LAI) formulations of second-generation antipsychotics, according to a report in AJP in Advance. The findings, which also revealed that patients who were taking multiple antipsychotics (polypharmacy) had lower discontinuation rates, were based on data from the U.S. Department of Veterans Affairs (VA).Though the data was limited to veterans, lead author Marc Weiser, M.D., head of the Division of Psychiatry at Sheba Medical Center in Ramat Gan, Israel, noted the findings mirrored those of a 2017 study that used Swedish medical data. “Replicating research findings is difficult,” Weiser noted. “When you have nearly identical outcomes from two studies done by different investigators in different countries using different patient populations, it points to the results being broadly applicable.”Weiser and colleagues compiled VA clinical and pharmacy data from all patients who received a schizophrenia diagnosis and at least one antipsychotic prescription lasting 60 days or more between October 2010 and September 2015. To keep the data robust, the investigators focused on antipsychotics with at least 150 prescriptions during the analysis period. The final sample included 37,368 patients with 62,056 antipsychotic prescriptions among 15 categories: nine oral medications (aripiprazole, clozapine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, and all first-generation antipsychotics), five LAI formulations (first-generation drugs fluphenazine and haloperidol and second-generation aripiprazole, paliperidone, and risperidone), and patients receiving polypharmacy.The investigators compared the treatment discontinuation rates and hospital admission rates associated with all the medications relative to olanzapine. Weiser noted olanzapine was chosen as the reference since it is considered the most well-tolerated oral antipsychotic and it was used as the reference drug in the 2017 Swedish study.After adjusting for patient sociodemographic factors, Weiser and colleagues found that five groups had a lower risk of treatment discontinuation than olanzapine. These included patients taking clozapine (with nearly 60% less discontinuation risk than olanzapine), a trio of second-generation LAIs (aripiprazole, paliperidone, and risperidone), and patients on polypharmacy. Patients taking oral quetiapine, oral ziprasidone, oral aripiprazole, oral risperidone, and oral first-generation antipsychotics all had higher risks of discontinuation than those taking olanzapine. In a secondary analysis, the investigators found that all three second-generation LAIs were associated with lower risks of discontinuation with the oral formulations of the medications.Weiser told Psychiatric News that he was not surprised by the findings that clozapine was associated with a lower risk of treatment discontinuation than the other antipsychotics. “Since clozapine requires patients to check in regularly, physicians tend to prescribe it to patients who they believe will be compliant; there is a pre-screening process built in.”The polypharmacy findings were a bit more surprising, he noted. “Giving patients multiple antipsychotics is considered a no-no in clinical settings, but this finding supports that giving the right combination of drugs can boost their effectiveness,” he said. Future studies should look at which combinations may offer the most symptom improvement along with lowest risks of side effects.In contrast to the discontinuation findings, none of the medications were found to reduce the risk of psychiatric hospitalization compared with olanzapine. Weiser noted this was the one of the few divergences from the Swedish study, which found clozapine to be superior to olanzapine.While no antipsychotics were superior to olanzapine in terms of hospitalizations, several were associated with increased hospitalization risk: these included oral and LAI first-generation antipsychotics, as well as oral lurasidone, quetiapine, and ziprasidone.Weiser noted that he was particularly concerned about the quetiapine finding, being that this was the second most-prescribed medication in the sample (behind oral risperidone) and this medication was associated with a 36% increased risk of hospitalization. “It is interesting since in the general population, quetiapine is not used that extensively for schizophrenia,” he said. Rather, quetiapine is more commonly prescribed off-label for conditions like anxiety or insomnia.This study was supported by the Stanley Medical Research Institute. Weiser also serves on the staff of the Stanley Institute. ■“Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs” is posted here.The 2017 analysis, “Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia” is posted here. ISSUES NewArchived