Polypharmacy Associates With Decreased Hospitalization Risk in Schizophrenia

Compared with antipsychotic monotherapy, antipsychotic polypharmacy tended to be associated with lower risk for hospitalization for severe physical health problems. These results were published in the American Journal of Psychiatry.

Data for this study were sourced from the nationwide Hospital Discharge register and linked databases in Finland. Patients (N=61,889) with schizophrenia who were hospitalized between 1972 and 2017 and who were still alive through January 1996 were evaluated for hospitalizations between 1996 and 2017 on the basis of receipt of antipsychotic medication.

Patients had a mean age of 46.7 (SD, 16.0) years, 50.3% were men, and they had been diagnosed with schizophrenia 8.8 (SD, 9.0) years previously.

The most common antipsychotic regimens were olanzapine monotherapy dosed at 1.6 defined daily dose (DDD)/day or greater (18.4%), followed by clozapine monotherapy dosed at 1.1-<1.4 DDD/day (14.3%), and clozapine monotherapy dosed at 0.6-<0.9 DDD/day (13.1%). Among polypharmacies, olanzapine-quetiapine dosed at 1.6 DDD/day or greater (5.4%) and clozapine-aripiprazole dosed at 1.6 DDD/day or greater (4.3%) were the most common regimens.

Stratified by monotherapy and polypharmacy classes in 7 DDD groups, 6 out of the 7 dosages of monotherapy associated with an increased risk for nonpsychiatric hospitalizations (adjusted hazard ratio [aHR] range, 1.04-1.37; all P ≤.0141) with higher doses tending to associate with higher risk whereas the lowest (<0.4 DDD/day; aHR, 1.14; P <.0001) and 3 highest (≥1.1 DDD/day; aHR range, 1.04-1.19; all P ≤.0339) dose categories of polypharmacy associated with higher risk.

Hospitalizations for cardiovascular causes were only related with the highest dose category (≥1.6 DDD/day) for both monotherapy (aHR, 1.45; P <.0001) and polypharmacy (aHR, 1.19; P =.0009).

Among patients using polypharmacy, risk for nonpsychiatric hospitalizations were elevated for individuals taking polypharmacy doses of <0.4 DDD/day (aHR, 1.07; P =.0207) but decreased for those taking 0.6-<0.9 (aHR, 0.94; P =.0038) 1.1-<1.4 (aHR, 0.91; P <.0001), 1.4-<1.6 (aHR, 0.91; P =.0015), and ≥1.6 (aHR, 0.87; P <.0001) DDD/day compared with monotherapy. For cardiovascular hospitalizations, patients taking polypharmacy and monotherapy were at similar risks, with the exception that polypharmacy at the highest dose was associated with lower risk compared with monotherapy (aHR, 0.82; P =.0035).

In a secondary analysis, risk for psychiatric hospitalizations were evaluated. In general, any polypharmacy associated with a 6% lower risk for psychiatric hospitalizations compared with monotherapy (aHR, 0.94).

The findings of this study may not be generalizable for a more diverse population.

These data indicated that among individuals with schizophrenia, polypharmacy was generally associated with more favorable hospitalization outcomes than monotherapy. Study authors concluded, “The current recommendations of treatment guidelines categorically encouraging use of monotherapy instead of polypharmacy are not based on evidence and should take a more agnostic approach to this issue.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.