TY - JOUR
T1 - Body weight gain in clozapine-treated patients: Is norclozapine the culprit?
AU - Jessurun, Naomi T.
AU - Derijks, Hieronymus J.
AU - van Marum, Rob J.
AU - Jongkind, Amy
AU - Giraud, Eline L.
AU - van Puijenbroek, Eugène P.
AU - Grootens, Koen P.
N1 - Publisher Copyright: © 2021 British Pharmacological Society Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - body mass index
KW - body weight gain
KW - clozapine
KW - norclozapine
KW - waist circumference
UR - http://www.scopus.com/inward/record.url?scp=85111848113&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/bcp.14992
DO - https://doi.org/10.1111/bcp.14992
M3 - Article
C2 - 34355423
SN - 0306-5251
JO - British journal of clinical pharmacology
JF - British journal of clinical pharmacology
ER -