Antipsychotic Polytherapy is Not Good

So, I'm writing about a topic which is of great interest to me. For a number of years, I was the chair of the Pharmacy and Therapeutics committee at a large state psychiatric hospital. One of our biggest challenges was dealing with the costs of antipsychotic polytherapy, especially the use of multiple second generation antipsychotic drugs. I also had a large clinical practice at the same institution. As a result of seeing many patients taking such polytherapy, I developed the strong impression that antipsychotic polytherapy rarely produced efficacy superior to monotherapy, and was often associated with a higher adverse effect burden. There is substantial literature support for this opinion.

A recent poster presentation at the ISCR 2009 meetings in San Diego adds to the data available on this subject. The authors evaluated 425 outpatients with severe, persistent mental illness, of which 112 (26%) were taking multiple antipsychotics. The mean antipsychotic dosage was nearly twice the "defined daily dosage" (per WHO), suggesting that the premise that multiple antipsychotic therapy permits use of lower dosing is false. Further, over twice as many polytherapy patients were treated with anticholinergic agents, which is evidence that the motor adverse effects associated with polytherapy are not less than with monotherapy. The patients in this study were on stable medication regimens for at least 90 days. Thus, the patient cohort likely eliminated patients in the midst of a titration/taper paradigm. This reduces the potential for bias in patie nt selection which plagues some other studies of this matter.

This is of potentially great significance in neuropsychopharmacology. As the cohort was outpatients, this negates the argument that patients requiring such therapy are the most refractory inpatients. I look forward to the release of a more detailed print publication.

Antipsychotic polytherapy is expensive. The doses required for polytherapy may be higher, not lower than with monotherapy. There is no compelling evidence that efficacy is superior. Adverse effects may be worse. As with many other drug classes, therapeutic parsimony is recommended.