Antipsychotic polypharmacy prevalent despite efficacy doubts

Results of a retrospective study suggest that around a quarter of patients with schizophrenia receive antipsychotic polypharmacy, despite a lack of evidence for the approach.

Kathleen Villa (Jazz Pharmaceuticals, Palo Alto, California, USA) and colleagues analysed data on 4156 patients with schizophrenia who belonged to an employer-based health plan. They found that 968 (23.3%) patients received two or more antipsychotic drugs within 90 days of each other during 1-year follow-up.

Patients receiving polypharmacy were more likely to discontinue treatment (defined as a 90-day gap in at least one antipsychotic medication) during follow-up, at a rate of 77% compared with 54% in the monotherapy group. Accordingly, the average duration of therapy was also significantly shorter, at 163.8 versus 252.7 days.

The authors also note a greater proportion of patients with severe disease in the polypharmacy group than in the monotherapy group (65.5 vs 50.5%). And in the study population, who were aged between 13 and 64 years, those receiving polypharmacy were significantly younger at a mean of 37.8 years compared with 40.3 years in those receiving monotherapy. Polypharmacy patients also had significantly higher use of other medications than those in the monotherapy group.

“Current clinical practice commonly involves combining antipsychotics to improve treatment of patients with suboptimally controlled symptoms of schizophrenia, despite the lack of robust evidence for this approach, the increased risk of side effects, and the cost implications”, explain Villa and colleagues in BMC Psychiatry.

While physicians may combine antipsychotics in order to try and reduce overall dosage, evidence has linked polypharmacy to greater overall antipsychotic dose as well as side effects and an increased risk of drug interactions. It is generally discouraged by guidelines, Villa et al note.

The team observes that in older patients, it appeared that treatment was more concordant with guidelines, as these patients were more likely to be trialled on alternative antipsychotics as monotherapy before moving onto polypharmacy. However, among younger patients, there was a different pattern, with patients typically receiving combinations of second-generation antipsychotics and having an additional antipsychotic added to their failed monotherapy, rather than starting two new medications.

“Although it is understandable that physicians want to control severe acute symptoms of schizophrenia, particularly early in the course of disease, long-term use of polypharmacy beginning at an early age may pose additional risk to patients and warrants further study”, say Villa and team.

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