Overview
Serotonin reuptake inhibitor (SRI) antidepressants are primary pharmacologic treatments for major depressive and anxiety disorders 1. Genetic variations in drug-metabolizing enzymes and pharmacodynamic genes can influence their metabolism, potentially affecting dosing, efficacy, and tolerability 1.Diagnosis
Management
Genetic variation in CYP2D6, CYP2C19, and CYP2B6 influences the metabolism of many SRI antidepressants, potentially affecting dosing, efficacy, and tolerability 1.
Recommendations exist for using CYP2D6, CYP2C19, and CYP2B6 genotype results to inform prescribing of these antidepressants 1.
Data for SLC6A4 and HTR2A genotypes do not currently support their clinical use in antidepressant prescribing 1.Special Populations
SSRIs may have different pharmacokinetic parameters in patients <18 years of age compared to adults, impacting effectiveness and tolerance 2.
Fluoxetine, fluvoxamine, or paroxetine concentrations can be approximately two times higher in children than in adolescents and adults, requiring dose adjustments 2.
In patients <18 years of age with significant challenges in drug selection or dosing due to efficacy or tolerance issues, examining dominant polymorphisms for isoenzyme metabolism may be important 2.
SSRIs are generally well tolerated in patients <18 years of age, with most adverse reactions being mild or moderate 2.
Rates of suicidal ideation during SSRI treatment in patients <18 years of age are comparable to placebo, with rare suicide attempts occurring in both active and placebo groups 2.
There was no statistically significant increased risk for antidepressants (including all SSRIs) or psychotherapy, or combinations, except for venlafaxine 2.Key Recommendations
Genetic variation in CYP2D6, CYP2C19, and CYP2B6 influences the metabolism of many SRI antidepressants, potentially affecting dosing, efficacy, and tolerability 1. (Evidence: Moderate)
Recommendations are available for using CYP2D6, CYP2C19, and CYP2B6 genotype results to inform prescribing of these antidepressants 1. (Evidence: Moderate)
In patients <18 years of age with significant challenges in drug selection or dosing due to efficacy or tolerance issues, examining dominant polymorphisms for isoenzyme metabolism may be important 2. (Evidence: Moderate)References
1 Bousman CA, Stevenson JM, Ramsey LB, Sangkuhl K, Hicks JK, Strawn JR et al.. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants. Clinical pharmacology and therapeutics 2023. link
2 Janas-Kozik MH, Słopień A, Remberk B, Siwek M. The place of selective serotonin reuptake inhibitors (SSRIs) in the treatment of depressive disorders in children and adolescents. Recommendations of the Main Board of the Polish Psychiatric Association. Part 2 - pharmacological properties and safety of use. Psychiatria polska 2023. link