A neutrophil-to-lymphocyte ratio higher than 3 may identify infl ammation during clozapine titrations: A re-analysis of five published cases of myocarditis.

OBJECTIVES

The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation. A NLR≥3 is considered abnormal (and ≥1.8 for benign ethnic neutropenia, BEN).

METHODS

NLR values were added to longitudinal data including c-reactive protein (CRP) in 5 published clozapine-induced myocarditis cases.

RESULTS

Case 1 had two NLRs with normal values, but on clozapine day 19, the CRP became abnormal (10.0 μg/d, ≤0.9) and the NLR=3.9. Clozapine was stopped on day 26. Case 2 had three normal NLRs before myocarditis, but on day 19 clozapine was stopped due to abnormal CRP (16. μg/dL, ≤0.9) with abnormal NLR (6.7). Case 3 received 25 mg on the first day (on valproic acid and quetiapine) with a NLR=3.4 on day 2. On day 11, CRP and NLR were normal. On day 14, he had chest pain, abnormal CRP (4.9 μg/dL,≤0.9) and abnormal NLR (7.4). Clozapine was discontinued on day 17. CRP and NLR finally normalized on day 35. Skin abscesses led to abnormal CRP and NLR values. On day 148, 12.5 mg of clozapine was restarted leading to a skin rash the next day. On day 155, this dose was stopped. Case 4 had two normal NLRs before myocarditis, but on day 16, clozapine was stopped (abnormal CRP, 15.8 μg/dL, ≤0.5 and abnormal NLR=4.4). Case 5 had BEN. NLR was normal on day 7, but became abnormal (NLR=1.9) on day 11 on 250 mg/day. He died five days later.

CONCLUSIONS

An abnormal NLR during titration may suggest clozapine-induced inflammation and/or infection. (Neuropsychopharmacol Hung 2025; 27(4): 296-311)