Should we routinely add CRP to clozapine titrations? – Learning from three cases

Translated title of the contribution: Should we routinely add CRP to clozapine titrations? – Learning from three cases

Charles Shelton, Can Jun Ruan, Aygün Ertuğrul, Robert O. Cotes, Jose DE LEON

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Objectives: An international guideline recently provided certain personalized schedules for titrating clozapine in adult inpatients by considering: 1) DNA ancestry group, 2) sex-smoking subgroup, and 3) presence/absence of clozapine poor metabolizer (PM) status. Measuring CRP levels at baseline and during the first 4 weeks is recommended. Titrations too fast for the metabolism of specific patients can lead to clozapine-induced inflammations and CRP elevations. Methods: Three published cases are reinterpreted. Better outcomes might have been obtained by using the guideline. Results: Case 1 was a Chinese male non-smoker, a clozapine PM due to an underlying inflammation. Case 2 was a Turkish female non-smoker who developed clozapine-induced myocarditis in the context of 4 risk factors (undiagnosed inflammation, obesity, valproate and olanzapine co-prescription). Case 3 was a United States patient of European ancestry with no known risk factors who developed myocarditis after a routine titration and had an unsuccessful rechallenge with 12.5 mg/day. Application of the international clozapine titration guideline may have prevented: 1) Case 1 by recommending against clozapine titration for a patient with an abnormal CRP level, 2) Case 2 by considering 4 risk factors and using a slow titration for clozapine PMs, and 3) Case 3 by using CRP elevations for early identification of a possible genetic PM. Conclusions: When baseline or prior CRPs are normal and then become abnormal during a clozapine titration, this indicates: 1) clozapine-induced inflammation associated with too-rapid titration for that specific patient, and/or 2) co-occurrence of an infection. Prospective studies need to verify this hypothesis. (Neuropsychopharmacol Hung 2022; 24(4): 153–161).

Translated title of the contributionShould we routinely add CRP to clozapine titrations? – Learning from three cases
Original languageEnglish
Pages (from-to)153-161
Number of pages9
JournalNeuropsychopharmacologia Hungarica
Issue number4
StatePublished - Dec 2022

Bibliographical note

Publisher Copyright:
© 2022, Hungarian Association of Psychopharmacology. All rights reserved.


  • CYP1A2
  • clozapine/adverse effects
  • clozapine/blood
  • clozapine/metabolism
  • inflammation
  • myocarditis/chemically induced
  • myocarditis/etiology

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuropsychology and Physiological Psychology
  • General Pharmacology, Toxicology and Pharmaceutics
  • General Neuroscience


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