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Comparison of the effects of different routes of antipsychotic administration on pharmacokinetics and pharmacodynamics.

Clinicians face a dilemma when choosing between short-acting atypical antipsychotics and long-acting conventional antipsychotics. Atypical antipsychotics offer better safety and efficacy, while depot formulations of conventional antipsychotics provide more reliable drug delivery, reduced differences in peak and trough plasma levels of drug, and greater dosing precision. Risperidone was recently approved by the U.S. Food and Drug Administration as the first atypical long-acting antipsychotic medication, given as biweekly gluteal injections. This long-acting formulation is synthesized using a microsphere encapsulation process, and gradual hydrolysis of the copolymer encapsulating the drug provides a steady release of medication. Consistent with other long-acting medications, plasma drug level fluctuation is reduced more with long-acting than with oral risperidone. Analyses are currently underway to further examine safety outcomes with long-acting risperidone.