title: Olanzapine: a systematic review and meta-regression of the relationships between dose, plasma concentration, receptor occupancy, and response.
abstract: OBJECTIVE
  To conduct a systematic review examining the relationships between olanzapine dose, clinical outcome, dopamine occupancy, and plasma concentration; and to evaluate the potential for therapeutic drug monitoring.
  
  
  METHODS
  A search using Embase, Medline, and Pubmed was conducted; and the literature was systematically reviewed. Studies meeting inclusion criteria were examined. The relationships between olanzapine dose, response, dopamine occupancy, and concentration were analyzed using statistical regression.
  
  
  RESULTS
  Ten studies were included in the analysis for dose-response. The effect size-dose relationship showed a typical dose-response curve with minimal rise in slope for doses higher than 10 mg/d. For the dose-occupancy relationship, 6 studies were included. Doses more than approximately 12 mg/d were sufficient to block 65% of striatal D2 receptors. Doses higher than 20 mg led to minimally higher receptor occupancies. Fifteen studies were included in the meta-regression of olanzapine mean concentrations. A linear relationship between mean plasma concentration and mean dose was observed.
  
  
  CONCLUSIONS
  Our review suggests that the likelihood of a favorable response with olanzapine is maximized at doses of 10 to 15 mg/d (perhaps lower in nonsmoking females). Higher doses may be considered if 15 mg is ineffective and if plasma level is less than 20 ng/mL on that dose. There is a direct linear relationship between olanzapine dose and plasma concentration. Therapeutic drug monitoring may be useful in patients who are suspected of nonadherence, where there is potential for a drug interaction, and in patients taking 15 mg/d or more and who have not reached clinical response.
authors.affiliation: Pharmacy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, UK.
authors.forename: Delia
authors.initials: D
authors.lastname: Bishara
authors.forename: Olubanke
authors.initials: O
authors.lastname: Olofinjana
authors.forename: Anna
authors.initials: A
authors.lastname: Sparshatt
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.forename: David
authors.initials: D
authors.lastname: Taylor
authors.forename: Maxine X
authors.initials: MX
authors.lastname: Patel
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D001569:Benzodiazepines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D000077152:Olanzapine; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012044:Regression Analysis; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D001569:Benzodiazepines; D000077152:Olanzapine