Does Olanzapine Warrant Clinical Pharmacokinetic Monitoring in Schizophrenia?

Olanzapine, a second-generation antipsychotic, is a first-line agent in the treatment of schizophrenia. The objective of this review was to determine whether olanzapine warrants clinical pharmacokinetic monitoring in patients with schizophrenia, using a previously published decision-making algorithm. Although olanzapine is an appropriate therapy for patients with schizophrenia and is readily measurable in biological fluids, significant interindividual variation exists in its pharmacokinetics. While the duration of therapy is expected to be long term, the correlation of olanzapine concentrations with efficacy and toxicity has not been well defined in the literature. There are multiple tools readily available for the assessment of efficacy in schizophrenia, and clinical signs and symptoms can be used to monitor both for efficacy and for adverse effects. Therefore, routine monitoring of olanzapine concentrations does not appear warranted in the general schizophrenic population. However, patients in whom a change in olanzapine pharmacokinetics is expected — such as during addition or removal of an enzyme-inducing or -inhibiting drug, or during initiation or cessation of smoking — may benefit from clinical pharmacokinetic monitoring, as would patients in whom non-compliance is suspected. Patients who fail to respond to maximum recommended doses and those who experience adverse effects from therapeutic doses may also benefit from therapeutic drug monitoring, as they may have inherent variations in hepatic enzyme activity. However, in the population at large who suffer from schizophrenia, monitoring of olanzapine concentrations is not expected to offer additional benefit beyond appropriate clinical monitoring alone.