ICSR 2009: Polypharmacy With Antipsychotics Not Beneficial, Potentially Hazardous

Norra MacReady

April 03, 2009

April 3, 2009 (San Diego, California) — Persistent polypharmacy and excessive dosing with antipsychotics is common among mentally ill outpatients, even though it is not endorsed by treatment guidelines, according to a new study.

"The take-away message is that there is no reliable evidence in the literature that antipsychotic polypharmacy is more effective than monotherapy, and, given the cost and the increased risk of side effects, it's something clinicians should think about carefully," lead author Alasdair M. Barr, PhD, from the University of British Columbia, in Vancouver, said at a poster presentation at the 2009 International Congress on Schizophrenia Research.

Dr. Barr and colleagues surveyed 435 outpatients with severe and persistent mental illness who had been on the same medication regimen for at least 90 days. The illnesses covered were schizophrenia, schizoaffective disorder, major depression, bipolar disorder, and psychosis not otherwise specified (NOS).

The investigators also determined the prevalence of excessive dosing by dividing each patient's prescribed daily dose (PDD) of antipsychotics by the defined daily dose (DDD) established by the World Health Organization. It defines the DDD as the assumed average daily maintenance dose given for the drug's main indication.

A PDD/DDD ratio of 1 indicates that the prescribed daily dose equals the defined daily dose, explained Dr. Barr. A ratio greater than 1 suggests that the prescribed dose is greater than the DDD. In keeping with the practice of other investigators, they used a PDD/DDD ratio 1.5 or greater as evidence of excessive dosing.

Polypharmacy Associated With Higher Doses

A total of 112 patients, or 26% of the sample, were being treated with antipsychotic polypharmacy. The mean PDD/DDD ratio for those patients was 1.94, compared with a mean ratio of .94 for the patients treated with monotherapy (P < .005), a relationship that persisted across diagnoses. Clinicians sometimes justify the use of polypharmacy by saying that it allows them to prescribe lower doses of each drug, but "this doesn't seem to stand up to analysis, at least in our study," Dr. Barr said. He believes this study is the first to show a relationship between polypharmacy and excessive dosing.

Scores on the Global Assessment of Functioning scale did not differ significantly between the groups, suggesting that polypharmacy had little if any clinical benefit over monotherapy.

However, Dr. Barr warned that he and his colleagues have not yet examined clinical outcomes with any other measures, such as the Positive and Negative Syndrome Scale (PANSS).

They also did not directly examine the incidence of complications. However, 29.5% of the polypharmacy patients also were using anticholinergic agents, compared with 13.3% of the patients on monotherapy (P < .001), which suggests that polypharmacy may be associated with a higher incidence of extrapyramidal adverse effects, Dr. Barr pointed out. The groups did not differ significantly in their use of other drugs such as antidepressants, lipid-lowering agents, or antidiabetics.

Longitudinal Data Important

These findings are meaningful because the patients were on these drug regimens for at least 90 days, said Jennifer Yee Man Tang, a postgraduate student at the University of Hong Kong, who has conducted similar but unrelated research.

She explained that most studies of drug regimens prescribed to mentally ill people are cross-sectional, meaning that they capture data only at single points in time. This makes it "hard to know how the drug prescriptions changed over time." For example, patients may be on several medications only briefly if their doctor is weaning them off 1 agent while introducing another. Thus, "it's crucial to have longitudinal data, because we can see patients at different stages and see their response to treatment and side effects."

2009 International Congress on Schizophrenia Research: Poster 103. Presented April 1, 2009.