Dataset Information

Clinical Impact of Functional CYP2C19 and CYP2D6 Gene Variants on Treatment with Antidepressants in Young People with Depression: A Danish Cohort Study.

ABSTRACT:

Background

The clinical impact of the functional CYP2C19 and CYP2D6 gene variants on antidepressant treatment in people with depression is not well studied. Here, we evaluate the utility of pharmacogenetic (PGx) testing in psychiatry by investigating the association between the phenotype status of the cytochrome P450 (CYP) 2C19/2D6 enzymes and the one-year risks of clinical outcomes in patients with depression with incident new-use of (es)citalopram, sertraline, or fluoxetine.

Methods

This study is a population-based cohort study of 17,297 individuals who were born between 1981 and 2005 with a depression diagnosis between 1996 and 2012. Using array-based single-nucleotide-polymorphism genotype data, the individuals were categorized according to their metabolizing status of CYP2C19/CYP2D6 as normal (NM, reference group), ultra-rapid- (UM), rapid- (RM), intermediate- (IM), or poor-metabolizer (PM). The outcomes were treatment switching or discontinuation, psychiatric emergency department contacts, and suicide attempt/self-harm. By using Poisson regression analyses, we have estimated the incidence rate ratios (IRR) with 95% confidence intervals (95% CI) that were adjusted for covariates and potential confounders, by age groups (<18 (children and adolescents), 19-25 (young adults), and 26+ years (adults)), comparing the outcomes in individuals with NM status (reference) versus the mutant metabolizer status. For statistically significant outcomes, we have calculated the number needed to treat (NNT) and the number needed to genotype (NNG) in order to prevent one outcome.

Results

The children and adolescents who were using (es)citalopram with CYP2C19 PM status had increased risks of switching (IRR = 1.64 [95% CI: 1.10-2.43]) and suicide attempt/self-harm (IRR = 2.67 [95% CI; 1.57-4.52]). The young adults with CYP2C19 PM status who were using sertraline had an increased risk of switching (IRR = 2.06 [95% CI; 1.03-4.11]). The young adults with CYP2D6 PM status who were using fluoxetine had an increased risk of emergency department contacts (IRR = 3.28 [95% CI; 1.11-9.63]). No significant associations were detected in the adults. The NNG for preventing one suicide attempt/suicide in the children who were using (es)citalopram was 463, and the NNT was 11.

Conclusion

The CYP2C19 and CYP2D6 PM phenotype statuses were associated with outcomes in children, adolescents, and young adults with depression with incident new-use of (es)citalopram, sertraline, or fluoxetine, therefore indicating the utility of PGx testing, particularly in younger people, for PGx-guided antidepressant treatment.

SUBMITTER: Thiele LS

PROVIDER: S-EPMC9318115 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveTo provide evidence on the effect of the COVID-19 pandemic on the mental health of young people who grew up in poverty in low/middle-income countries (LMICs).DesignA phone survey administered between August and October 2020 to participants of a population-based longitudinal cohort study established in 2002 comprising two cohorts born in 1994-1995 and 2001-2002 in Ethiopia, India (Andhra Pradesh and Telangana), Peru and Vietnam. We use logistic regressions to examine associations between mental health and pandemic-related stressors, structural factors (gender, age), and lifelong protective/risk factors (parent and peer relationship, wealth, long-term health problems, past emotional problems, subjective well-being) measured at younger ages.SettingA geographically diverse, poverty-focused sample, also reaching those without mobile phones or internet access.Participants10 496 individuals were approached; 9730 participated. Overall, 8988 individuals were included in this study; 4610 (51%) men and 4378 (49%) women. Non-inclusion was due to non-location or missing data.Main outcome measuresSymptoms consistent with at least mild anxiety or depression were measured by Generalized Anxiety Disorder-7 (≥5) or Patient Health Questionnaire-8 (≥5).ResultsRates of symptoms of at least mild anxiety (depression) were highest in Peru at 41% (32%) (95% CI 38.63% to 43.12%; (29.49-33.74)), and lowest in Vietnam at 9% (9%) (95% CI 8.16% to 10.58%; (8.33-10.77)), mirroring COVID-19 mortality rates. Women were most affected in all countries except Ethiopia. Pandemic-related stressors such as health risks/expenses, economic adversity, food insecurity, and educational or employment disruption were risk factors for anxiety and depression, though showed varying levels of importance across countries. Prior parent/peer relationships were protective factors, while long-term health or emotional problems were risk factors.ConclusionPandemic-related health, economic and social stress present significant risks to the mental health of young people in LMICs where mental health support is limited, but urgently needed to prevent long-term consequences.