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

• Published in: Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakológiai Egyesület lapja Vol. 24; no. 4; p. 153
• Main Authors: Shelton, Charles, Ruan, Can-Jun, Ertuğrul, Aygün, Cotes, Robert O, De Leon, Jose
• Format: Journal Article
• Language: English
• Published: Hungary 01-12-2022
• Subjects: Adult; Antipsychotic Agents - adverse effects; C-Reactive Protein; Clozapine - adverse effects; Female; Humans; Inflammation - chemically induced; Male; Myocarditis - chemically induced; Myocarditis - diagnosis; Prospective Studies; clozapine/metabolism; inflammation; CYP1A2; clozapine/blood; myocarditis/chemically induced; clozapine/adverse effects; myocarditis/etiology
• ISSN: 1419-8711

Objectives: An international guideline recently provided certain personalized schedules for titrating clozapine in adult inpatients by considering: 1) DNA ancestry group, 2) sexsmoking 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 infl ammation, 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.