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Certain Types of Antipsychotic Polypharmacy Feasible in Schizophrenia Treatment

March 06, 2019

Some types of antipsychotic polypharmacy appear to be associated with fewer psychiatric rehospitalizations compared with monotherapy among adults with schizophrenia, according to a study published online in JAMA Psychiatry.

“Although the results do not indicate that all types of polypharmacy are beneficial, the current treatment guidelines should modify their categorical recommendations discouraging all antipsychotic polypharmacy in the maintenance treatment of schizophrenia,” researchers wrote.

The nationwide cohort study included 62,250 adults with schizophrenia in Finland with follow-up data spanning 20 years. To minimize selection bias, researchers used within-individual analyses.

Combining aripiprazole with clozapine was associated with the lowest risk of psychiatric rehospitalization among all antipsychotic treatments, whether monotherapy or polypharmacy.

“We observed that when treatment for the same patient was switched back and forth between monotherapy and polypharmacy, the use of aripiprazole plus clozapine was associated with a 14% to 23% lower risk of psychiatric or all-cause hospitalization compared with clozapine monotherapy,” researchers wrote.

Clozapine was the only monotherapy among the 10 most effective treatments identified in the study. The least successful monotherapy was quetiapine.

Aggregate data showed any antipsychotic polypharmacy was associated with a 7% to 13% lower risk of rehospitalization compared with any antipsychotic monotherapy, researchers reported.

“Because add-on treatments are started when monotherapy is no longer sufficient to control for worsening of symptoms, it is likely that the effect sizes for polypharmacy are underestimates,” they added.

Jolynn Tumolo


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

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