SSRI-antipsychotic combination in psychotic depression: sertraline pharmacokinetics in the presence of olanzapine, a brief report from the STOP-PD study

OBJECTIVE: We recently reported an unexpected interaction between olanzapine and sertraline in a population being treated for psychotic depression. Contrary to knowledge of cytochrome p450 interactions sertraline increased apparent clearance of olanzapine by 30%. Here we examined the pharmacokinetics of sertraline in the same population. Existing studies suggest that sertraline apparent clearance is significantly increased in male subjects and suggested an age/sex interaction. METHODS: We studied subjects undergoing combination of sertraline/olanzapine treatment for psychotic depression in the Study of the Pharmacotherapy of Psychotic Depression. Nonlinear mixed effect modelling software was used to examine the sertraline pharmacokinetics, evaluating age, sex, race, and olanzapine exposure as covariates. RESULTS: Eighty-seven subjects (median age 62 years, 28 male subjects, 11 African-Americans) provided 138 samples for sertraline concentration. Olanzapine exposure had a 14.8-fold range. A one compartment model with combined residual error described the sertraline concentration data adequately. Half-life and sex effect on sertraline apparent clearance (males averaging 50% higher (p \u3c 0.005); 96.6 l/h vs 64.8 in female subjects) were similar to previous reports. No other covariate (age, race or olanzapine exposure) had a significant impact on apparent clearance, and no age/sex interaction emerged. CONCLUSION: Sertraline pharmacokinetics were similar to historical descriptions in populations not taking antipsychotics. Unlike our unexpected finding that sertraline increases olanzapine apparent clearance, olanzapine exposure had no impact on sertraline pharmacokinetics