Age Impacts Olanzapine Exposure Differently During Use of Oral Versus Long-Acting Injectable Formulations: An Observational Study Including 8,288 Patients

J Clin Psychopharmacol. 2018 Dec;38(6):570-576. doi: 10.1097/JCP.0000000000000961.


Purpose: Olanzapine is a commonly prescribed antipsychotic available as oral and long-acting injectable (LAI) formulations. Data are lacking on the use and safety of olanzapine-LAI in older patients. The aim of this study was to investigate the effect of increasing age on olanzapine exposure during oral versus LAI administration in a real-life setting.

Methods: This observational study was based on routine therapeutic drug monitoring data collected during 2005-2017. As a measure of exposure, absolute concentrations and concentration/dose ratios of olanzapine were defined as outcome variables. Linear mixed-model analyzes were used to allow for inclusion of multiple samples per patient and adjustment for covariate effects.

Results: Olanzapine concentrations and doses from 8,288 patients (21,378 measurements) were included. The number of patients on oral treatment was 7,893 (42%, 50 years or older), while 395 were using olanzapine-LAI (27%, 50 years or older). In contrast to oral use, where the dose-adjusted concentration of olanzapine increased significantly for patients 50 years or older (P < 0.001), increasing age had no effect on olanzapine concentration following LAI administration (P = 0.550). The effects of smoking habits and gender were equal in oral and olanzapine-LAI users.

Conclusion: While the dose-adjusted systemic exposure of olanzapine increases by age after oral administration, these novel findings from a large patient population show that systemic exposure of olanzapine-LAI is unaffected by age, probably due to the lacking influence of age-related changes in gastrointestinal absorption and/or presystemic metabolism. From a pharmacokinetic point of view, it is therefore no reason to restrict the use of olanzapine-LAI in older patients requiring long-term treatment.

Publication types

  • Observational Study

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Antipsychotic Agents / administration & dosage*
  • Antipsychotic Agents / blood
  • Delayed-Action Preparations
  • Female
  • Humans
  • Injections
  • Male
  • Mental Disorders / drug therapy*
  • Middle Aged
  • Olanzapine / administration & dosage*
  • Olanzapine / blood
  • Young Adult


  • Antipsychotic Agents
  • Delayed-Action Preparations
  • Olanzapine