Population pharmacokinetics of antipsychotics

Response to antipsychotics is highly variable, which may be due in part to differences in drug exposure. The CATIE trials reported overall high rates of discontinuation due to lack of efficacy and/or intolerable side effects for all antipsychotics. Overall, 74% of patients with schizophrenia (SZ) discontinued the study medication before 18 months; 64% of those assigned to olanzapine, 75% of those assigned to perphenazine, 82% of those assigned to quetiapine, 74% of those assigned to risperidone, and 79% of those assigned to ziprasidone. Similarly, the majority of patients with Alzheimer's disease (AD) discontinued their assigned treatment, and in fact the adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation. In the AD trial, there were no significant differences among treatments with regard to the time to discontinuation of treatment for any reason: olanzapine (median, 8.1 weeks), quetiapine (5.3 weeks), risperidone (7.4 weeks), and placebo (8.0 weeks). One reason for the high rates of discontinuation may relate to the wide variability in the pharmacokinetics of these drugs, which often results in differences in the pharmacodynamics, both in the response to a drug and the incidence of adverse effects. For example, if a patient clears a drug faster than average, they will experience lower drug levels and may not respond as well at the same dose.