Abstract | OBJECTIVE: Atypical antipychotics are linked to a higher incidence of metabolic side effects, including weight gain, dyslipidemia, and diabetes. In this study, we examined the prevalence and potential genetic predictors of metabolic side effects in 60 adult patients on clozapine. METHOD: RESULTS: More than half of the patients were obese (51%), had metabolic syndrome (52.5%), and 30.5% were overweight. There was a high prevalence of antipsychotic polypharmacy (61.9%). With multivariable linear regression analysis, LEP -2548G>A, LEPR c.668A>G, and HTR2C c.551-3008 C>G were identified as genetic predictors of body mass index (BMI) after considering effects of clozapine dose, blood level, and concurrent medications (adjusted R2 = 0.305). Metabolic syndrome was found to be significantly associated with clozapine level and CYP2C19*2 and LEPR c.668 G alleles. Clozapine levels in patients with metabolic syndrome were significantly higher compared to those without metabolic syndrome (1886 ± 895 vs. 1283 ± 985 ng/mL, P < 0.01) and were associated with the CYP2C19*2 genotype. No association was found between the genetic variants studied and lipid or glucose levels. CONCLUSION: This study confirms a high prevalence of metabolic side effects with clozapine and suggests higher clozapine level and pharmacogenetic markers in CYP2C19, LEP, LEPR, and HTR2C receptors as important predictors of BMI and metabolic syndrome.
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Authors | Kamini Vasudev, Yun-Hee Choi, Ross Norman, Richard B Kim, Ute I Schwarz |
Journal | Canadian journal of psychiatry. Revue canadienne de psychiatrie
(Can J Psychiatry)
Vol. 62
Issue 2
Pg. 138-149
(02 2017)
ISSN: 1497-0015 [Electronic] United States |
PMID | 27681143
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antipsychotic Agents
- Cytochrome P-450 Enzyme System
- Clozapine
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Topics |
- Adult
- Aged
- Antipsychotic Agents
(adverse effects)
- Clozapine
(adverse effects)
- Cross-Sectional Studies
- Cytochrome P-450 Enzyme System
(genetics)
- Drug-Related Side Effects and Adverse Reactions
(epidemiology, genetics)
- Female
- Humans
- Male
- Middle Aged
- Obesity
(chemically induced, genetics)
- Overweight
(chemically induced, genetics)
- Pharmacogenomic Testing
- Prevalence
- Psychotic Disorders
(drug therapy)
- Schizophrenia
(drug therapy)
- Young Adult
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