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Polypharmacy and Adverse Drug Reactions

To the Editor: I read with interest the article about antipsychotic polypharmacy by Kreyenbuhl and colleagues in the April issue ( 1 ). The authors concluded that the patients who were on long-term antipsychotic polypharmacy were more severely ill with psychotic symptoms. The inference was partly based on increased odds of hospitalization in the previous year among patients who received more than one antipsychotic drug.

Antipsychotic polypharmacy has been linked to a greater incidence of adverse reactions ( 2 ), which in turn may lead to increased hospitalizations ( 3 ). The average age of patients in the study was more than 50 years; thus the likelihood of hospitalizations as a result of medication side effects is even higher. Kreyenbuhl and colleagues also note that the patients who were receiving polypharmacy were taking more antianxiety medications, mood stabilizers, and anti-Parkinsonism drugs, which further increases the risk of adverse drug reactions. An important determining factor in hospital admissions related to adverse drug reactions among elderly persons is the number of drugs being taken ( 4 ).

Kreyenbuhl and colleagues acknowledged the possibility of increased incidence of adverse reactions but did not consider it as a confounding factor in the study. It is conceivable that the hospitalizations among patients taking more than one antipsychotic were a reflection of the adverse drug reactions rather than the severity of illness.

Antipsychotic polypharmacy is a widely prevalent practice without any robust evidence to back it up. More studies are needed before this practice can be justified on empirical grounds.

Dr. Babbar is affiliated with the Carilion-University of Virginia Roanoke Valley Psychiatry Program, Salem, Virginia.

References

1. Kreyenbuhl JA, Valenstein M, McCarthy JF, et al: Long-term antipsychotic polypharmacy in the VA health system: patient characteristics and treatment patterns. Psychiatric Services 58:489–495, 2007Google Scholar

2. Centorrino F, Goren JL, Hennen J, et al: Multiple versus single antipsychotic agents for hospitalized psychiatric patients: case-control study of risks versus benefits. American Journal of Psychiatry 161:700–706, 2004Google Scholar

3. Col N, Fanale JE, Kronholm P: The role of medication noncompliance and adverse drug reactions in hospitalizations of the elderly. Archives of Internal Medicine 150:841–845, 1990Google Scholar

4. Onder G, Pedone C, Landi F, et al: Adverse reaction as cause of hospital admission: results from Italian Group of Pharmacoepidemiology in the Elderly (GIFA). Journal of the American Geriatrics Society 50:1962–1968, 2002Google Scholar