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- Title
Body weight gain in clozapine‐treated patients: Is norclozapine the culprit?
- Authors
Jessurun, Naomi T.; Derijks, Hieronymus J.; van Marum, Rob J.; Jongkind, Amy; Giraud, Eline L.; van Puijenbroek, Eugène P.; Grootens, Koen P.
- Abstract
The antipsychotic drug clozapine is associated with weight gain. The proposed mechanisms include blocking of serotonin (5‐HT2a/2c), dopamine (D2) and histamine (H1) receptors. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2) to norclozapine, a metabolite with more 5‐HT2c‐receptor and less H1 blocking capacity. We hypothesized that norclozapine serum levels correlate with body mass index (BMI), waist circumference and other parameters of the metabolic syndrome. We performed a retrospective cross‐sectional study in 39 patients (female n = 8 (20.5%), smokers n = 18 (46.2%), average age 45.8 ± 9.9 years) of a clozapine outpatient clinic in the Netherlands between 1 January 2017 and 1 July 2020. Norclozapine concentrations correlated with waist circumference (r = 0.354, P =.03) and hemoglobin A1c (HbA1c) (r = 0.34, P =.03). In smokers (smoking induces CYP1A2), norclozapine concentrations correlated with waist circumference (r = 0.723, P =.001), HbA1c (r = 0.49, P =.04) and BMI (r = 0.63, P =.004). Elucidating the relationship between norclozapine and adverse effects of clozapine use offers perspectives for interventions and treatment options.
- Subjects
NETHERLANDS; WEIGHT gain; BODY weight; BODY mass index; WAIST circumference; SEROTONIN; DOPAMINE antagonists; ANTIPSYCHOTIC agents
- Publication
British Journal of Clinical Pharmacology, 2022, Vol 88, Issue 2, p853
- ISSN
0306-5251
- Publication type
Article
- DOI
10.1111/bcp.14992