WORKSHOP: Optimizing Treatment Outcomes for Clozapine with Therapeutic Drug Monitoring (TDM)

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Presenting Author(s): Dr. Pierre Chue, MBBCh, FRCPsych, LMCC, FRCPC, DABPN, MSc, CCST.

Co-Author(s): Vincent Agyapong, Adam Abba-Aji, Adegboyega Sapara, Mobilaji Lawal, Hany Shaltout

Date and time: 25 Mar 2023 from 13:25 to 13:45

Location: Hawthorn A  Floor Map

Learning Objectives

  1. Be introduced to therapeutic drug monitoring (TDM) and precision medicine;
  2. Understand how TDM can optimize antipsychotic treatment;
  3. Review the complexity of clozapine therapy in real-world examples.



Therapeutic Drug Monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. TDM informs on inter- & intra-individual variation of drug metabolism with additional benefit of safety data for drugs with narrow therapeutic index and is particularly relevant for psychiatric drugs and disorders.


Clozapine is the only medication approved for Treatment Resistant Schizophrenia (TRS). There is a high variability in clozapine plasma levels (CPLs) with a 50-fold inter-individual difference for the same dose reported. However, CPLs are not routinely ordered in most Canadian hospitals or clinics despite recommendation in the national guidelines.


A QI project evaluated CPLs in a real-world community population and compared with the established therapeutic reference range (350 – 600 ng/mL for single day dosing).


Patients in the Community Complex Psychosis Program undergo comprehensive evaluation including CPLs . Additional data recorded include age, sex, smoking status and concomitant medications.


In a community sample (n=16; aged 34 – 70 years) of 9 males (6 smokers) and 7 females (5 smokers), CPLs were found to range from 98 – 1262 ng/mL. There was minimal correlation with prescribed doses which ranged from 100 to 500 mg/day. Seven patients were determined to be in the therapeutic range; five were subtherapeutic; four were supratherapeutic with one patient above 1000 ng/mL.


This is the first real-world evaluation of CPLs in a community mental health setting. The large range of values reflects the complex metabolism of clozapine and the factors affecting its pharmacokinetics.

Literature References

  1. Schoretsanitis G, et al. J Clin Psych 2020;19;81(3):19cs13169.
  2. Khan AY, Preskorn SH. J Psychiatr Pract 2005;11(5):289-301.
  3. Buur-Ramussen B, Brosen K. Eur Neuropsychopharmacol 1999;9(6):453-9.
  4. Meyer JM, Stahl SM. Clozapine Handbook 2020.

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