Polypharmacy Possibly Superior to Monotherapy for Reducing Schizophrenia-Related Rehospitalization

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Researchers found that antipsychotic polypharmacy regimens correlated with a lower risk for rehospitalization vs any monotherapy in schizophrenia.

A study found that an aripiprazole plus clozapine combination regimen is associated with a lower risk for rehospitalization in patients with schizophrenia, suggesting that certain polypharmacy strategies may be more effective than monotherapy for reducing the risk for readmission in this patient population. Findings from the study were published in JAMA Psychiatry.

A hospital discharge register from Finland was used to form a nationwide cohort of patients with schizophrenia who were treated from 1996 to 2015 (n=62,250) with 29 different antipsychotic monotherapy and polypharmacy types. The investigators evaluated the risks for rehospitalization and the rates of all-cause hospitalization in this cohort. A secondary outcome included hospitalization due to physical illness and mortality. The researchers also compared the use of polypharmacy vs monotherapy in terms of psychiatric rehospitalization.

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While clozapine monotherapy was associated with the best outcomes, a combination of clozapine and aripiprazole was superior with regard to its lower risk for psychiatric rehospitalization (difference, 14%; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.79-0.94) in all polypharmacy periods. There was also an 18% difference in the conservatively defined polypharmacy analysis that excluded periods of <90 days (HR, 0.82; 95% CI, 0.75-0.89; P <.001). Differences were greater between clozapine plus aripiprazole vs clozapine monotherapy in patients with a first schizophrenia episode (difference, 22%; HR, 0.78; 95% CI, 0.63-0.96 [all polypharmacy periods] and difference, 23%; HR, 0.77; 95% CI, 0.63-0.95 [conservatively defined polypharmacy analysis]). Any antipsychotic polypharmacy regimen correlated with a 7% to 13% lower risk for rehospitalization vs any monotherapy (HR, 0.87; 95% CI, 0.85-0.88 to HR, 0.93; 95% CI, 0.91-0.95; P <.001).

Limitations of the analysis included the lack of data on concomitant psychosocial treatments, as well as potentially limited generalizability of the findings across high-income countries with a mostly white population.

The researchers suggest that their “results indicate that rational antipsychotic polypharmacy seems to be feasible by using 2 particular antipsychotics with different types of receptor profiles.”


Tiihonen J, Taipale H, Mehtälä J, Vattulainen P, Correll C, Tanskanen A. Association of antipsychotic polypharmacy vs monotherapy with psychiatric rehospitalization among adults with schizophrenia [published online February 20, 2019]. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2018.4320