Exposure to potentially dangerous drug-drug interactions involving antipsychotics

Antipsychotic drug therapy is the cornerstone of treatment of persons with schizophrenia. Because most antipsychotics are metabolized by the hepatic cytochrome P450 system, concomitant use of an antipsychotic and medications that are competitively metabolized by the same system may cause a potentially harmful drug-drug interaction. This study used a large state's Medicaid claims database to examine the proportion of patients exposed to such interactions and the risk factors associated with exposure.

Claims from January 2000 through December 2003 for adult patients with a diagnosis of schizophrenia and at least one prescription for an antipsychotic (N=27,909) were examined for pairs of medications identified as potentially causing moderate or severe adverse drug effects. Logistic regression models were estimated to determine potential risk factors associated with exposure to the interaction pairs.

A total of 6,417 (23%) patients were exposed to 14,213 potentially harmful interactions; 4,725 patients had at least one exposure from the same pharmacy, and 4,032 patients were exposed by the same physician. The greatest number of exposures (N=1,353) to potentially harmful combinations involved olanzapine and haloperidol. Patients prescribed risperidone were most likely to be exposed to an interaction (13.1%), followed by patients prescribed olanzapine (10.3%), quetiapine (3.3%), and clozapine (3.2%). A higher risk of exposure was associated with being female (odds ratio [OR]=.94), being white (OR=1.43), having depression (OR=1.21), or having impulse-control disorder (OR=1.98).

Interventions by physicians and pharmacies to reduce the prescribing and dispensing of potentially harmful pairs of medications to patients with schizophrenia are recommended.