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Drug Cocktails Still Common, Despite Treatment Guidelines

(Sept. 18, 2018) New research published this month in Psychiatric Services suggests that although there has been an overall decline in antipsychotic polypharmacy, the practice may still be common.


Mixing of multiple antipsychotic medications into a drug cocktail is only supposed to be utilized for patients with schizophrenia who are treatment-resistant after multiple different trials of antipsychotics, including clozapine. Polypharmacy is recommended only as a last resort treatment due to the limited evidence of its effectiveness in treatment for individuals with schizophrenia, as well as the elevated risk for side effects from the medications. In addition, the complicated treatment regimen may be more difficult for patients and result in lower treatment adherence.

Cynthia Fontenalla, PhD, and colleagues from Ohio State University analyzed Medicaid claims from 25,062 individuals with schizophrenia who were receiving antipsychotic medication from 2008-2014 in Ohio. Antipsychotic polypharmacy was defined in the study as the overlapping of any antipsychotic medications for more than 90 days, including first- and second-generation antipsychotics and clozapine. The researchers compared antipsychotic polypharmacy to a host of other variables, including age, sex, area of residence and clinical factors.

Study results

The authors report finding a statistically significant decline in antipsychotic polypharmacy over the six-year study period, decreasing from 29.5% of patients with schizophrenia in 2008 to 24.9% in 2014. Of the 2,886 individuals receiving two or more antipsychotic medications within the same three-month period in 2014, the majority of individuals were receiving two second-generation medications. Less than 15% of individuals receiving antipsychotic polypharmacy were on clozapine.

Individuals who identify as black or African American were significantly less likely to receive antipsychotic polypharmacy than white individuals, according to the results. Males, those with disabilities and those living in a rural setting were more likely to have long-term antipsychotic polypharmacy than others.

Individuals with schizophrenia who have frequent emergency department visits have a 1.36 higher risk of receiving multi-drug cocktails, whereas individuals who have higher rates of inpatient hospitalization are less likely to have received this treatment regimen.

These findings indicate that individuals who receive fragmented care in safety net systems are less likely to receive evidence-based and recommended treatment regimens. This highlights the importance of a continuum of care for individuals with schizophrenia that allows for appropriate, timely and effective coordinated treatment that goes beyond emergency department and other safety-net systems.

Elizabeth Sinclair

Director of Research


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