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Certain types of polypharmacy may be feasible in schizophrenia

Although not all types of polypharmacy will lead to fewer rehospitalizations than monotherapies, study findings showed that combining aripiprazole with clozapine was associated with the lowest risk for rehospitalization in patients with schizophrenia in Finland.

“Results from one large observational study have shown that any antipsychotic polypharmacy was associated with an approximately 40% lower risk of rehospitalization and death compared with any monotherapy, but the major problem in observational studies is residual confounding related to selection bias,” Jari Tiihonen, MD, PhD, from the Karolinska Institutet, Sweden, and colleagues wrote. “This limitation can be eliminated by using within-individual analyses in which each patient is used as his or her own control.”

The researchers investigated how specific antipsychotic combinations impacted psychiatric rehospitalization in a nationwide cohort study of 62,250 Finish patients with schizophrenia.

They used risk for psychiatric rehospitalization as a marker for relapse during the use of 29 different antipsychotic monotherapy and polypharmacy types within the same individual over a 20-year period. For the main analysis, researchers compared use of the following medications in monotherapy and as two-drug combinations with a time when no antipsychotic was used: oral risperidone, quetiapine, clozapine, olanzapine, aripiprazole, other oral formulations and any long-acting injectable agent.

Tiihonen and colleagues observed that patients with schizophrenia who received combination clozapine plus aripiprazole polypharmacy had the lowest risk for psychiatric rehospitalization. The risk was 14% lower than that for clozapine, the monotherapy associated with the best outcomes (HR = 0.86; 95% CI, 0.79-0.94).

In a conservatively defined polypharmacy analysis that excluded periods shorter than 90 days, the researchers observed even greater superiority of clozapine plus aripiprazole over clozapine monotherapy (difference, 18%; HR = 0.82; 95% CI, 0.75-0.89). In addition, the risk for rehospitalization was 13% lower during any polypharmacy than any monotherapy treatment (HR = 0.87; 95% CI, 0.85-0.88), according to the results.

“Our results on mortality are in line with those of previous cohort studies, showing lower mortality during antipsychotic polypharmacy than monotherapy,” Tiihonen and colleagues wrote.

The researchers also found that in patients with first-episode schizophrenia, these differences between clozapine plus aripiprazole vs. clozapine monotherapy were greater both in analysis including all polypharmacy periods (22% lower) as well as in the conservatively defined polypharmacy analysis (23% lower). Furthermore, when assessed at the aggregate level, they found that use of any antipsychotic polypharmacy was tied to a 7% to 13% lower risk for rehospitalization compared with any monotherapy.

“These results indicate that rational antipsychotic polypharmacy seems to be feasible by using two particular antipsychotics with different types of receptor profiles,” the researchers concluded. “The current treatment guidelines should modify their categorical recommendations discouraging all antipsychotic polypharmacy in the maintenance treatment of schizophrenia. – by Savannah Demko

Disclosures: Tiihonen reports participating in grant-funded projects from Eli Lilly and Janssen-Cilag. He also reports personal fees from the Finnish Medicines Agency, European Medicines Agency, Eli Lilly, Janssen-Cilag, Lundbeck, and Otsuka as well as grants from the Sigrid Jusélius Foundation and the Stanley Foundation. Please see the study for all other authors’ relevant financial disclosures.