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Psychiatrist.comTherapeutic Reference Range for Olanzapine in Schizophrenia: Systematic Review on Blood Concentrations, Clinical Effects, and Dopamine Receptor Occupancy

How could the newly defined reference range of 20-40 ng/mL for olanzapine impact the precision of schizophrenia treatment?

In an extensive review to refine the therapeutic reference range for olanzapine in the treatment of schizophrenia, this study investigated the association between blood olanzapine levels, clinical effects, and dopamine D2-receptor occupancy. Through a systematic search of various databases and a detailed analysis of 34 qualitative and 13 quantitative studies, the research pinpoints the optimal concentration levels for both oral and long-acting injectable (LAI) formulations.

Study Design:

  • Objective: Revising the therapeutic reference range for olanzapine in relation to clinical outcomes and D2-receptor occupancy
  • Sources: MEDLINE (PubMed), Web of Science, PsycINFO, Cochrane Library (March to December 2021)
  • Selection: 2,824 articles identified; 34 for qualitative synthesis, 13 for quantitative analysis
  • Language and Exclusion: Only English and German studies; non-human data excluded
  • Review Protocol: Following previously published protocol and PRISMA guidelines

Key Findings:

  • Relationship between blood olanzapine level and efficacy/side effects considered low (Level C)
  • Therapeutic thresholds: around 20 ng/mL for olanzapine 12 hours post-dose
  • Optimal drug efficacy: 65%–80% D2-receptor occupancy between 17 and 44 ng/mL
  • Side effects such as weight gain may occur at therapeutic levels


  • Suggested therapeutic reference range: 20–40 ng/mL for olanzapine oral and LAI formulations
  • In this range, optimal treatment for schizophrenia spectrum disorders expected
  • Higher plasma concentrations generally well tolerated, dose reduction not necessarily required

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Did You Know?
Schizophrenia affects approximately 1% of the global population, making it one of the leading causes of disability.

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