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Escitalopram

Antidepressants - SSRI

Drug Overview

Escitalopram, marketed under the brand name Lexapro, is a selective serotonin reuptake inhibitor (SSRI) commonly prescribed for mood and anxiety disorders.

Escitalopram is approved for the treatment of major depressive disorder and generalized anxiety disorder by helping to restore the balance of serotonin in the brain.

It works by blocking the serotonin transporter (SERT), preventing serotonin reuptake into presynaptic neurons, which increases serotonin availability in the synaptic cleft.

Relevant Genes and Their Roles

The primary gene involved in escitalopram metabolism is CYP2C19, which encodes an enzyme in the liver responsible for oxidative processing of many drugs.

Genetic variants in CYP2C19 can increase or decrease enzyme activity. Poor metabolizers have reduced function leading to slower drug clearance, whereas ultrarapid metabolizers clear the drug too quickly, reducing exposure. Metabolism refers to how your body processes and eliminates medications.

Impact of Genetics on Drug Response

Genetic variations in CYP2C19 categorize individuals into metabolizer phenotypes—ultrarapid, rapid, normal, intermediate, and poor—that influence escitalopram plasma levels, therapeutic efficacy, and risk of side effects by altering the rate of drug clearance.

Expected Clinical Effects of Genetic Variation

Ultrarapid/Rapid Metabolizer

  • Effect on drug levels: Significantly lower plasma concentrations due to increased metabolism.
  • Clinical consequence: Reduced likelihood of achieving therapeutic benefit.
  • Side effects: Fewer side effects; frequency and severity may be decreased.

Normal Metabolizer

  • Effect on drug levels: Expected standard plasma concentrations.
  • Clinical consequence: Standard therapeutic response when dosed appropriately.
  • Side effects: Typical side effect profile as seen in the general population.

Intermediate Metabolizer

  • Effect on drug levels: Moderately elevated plasma concentrations due to slower metabolism.
  • Clinical consequence: Potential for increased side effects at standard doses.
  • Side effects: Greater incidence of adverse effects; severity usually mild to moderate.

Poor Metabolizer

  • Effect on drug levels: Markedly increased plasma concentrations from very slow metabolism.
  • Clinical consequence: High risk of side effects and toxicity at standard doses.
  • Side effects: Frequent and potentially severe adverse effects.

Indeterminate/Not Available

  • Effect on drug levels: Unknown effect due to insufficient genotype information.
  • Clinical consequence: No specific guidance; follow standard dosing with clinical monitoring.
  • Side effects: Unknown; monitor per usual care.

Dosing Guidelines

The following dosing guidelines are based on the CPIC recommendations for escitalopram and CYP2C19 genotype.

CYP2C19 Dosing Guidelines

Phenotype Clinical Consequence Guideline Recommendation
Ultrarapid Metabolizer You may break down the drug too quickly, making it less effective. Consider a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19. If escitalopram is clinically appropriate and efficacy is not achieved at standard maintenance dosing, consider titrating to a higher maintenance dose.
Rapid Metabolizer You may process the drug faster, reducing its effects. Initiate therapy with recommended starting dose. If patient does not adequately respond, consider increasing the maintenance dose or switching to an alternative antidepressant not predominantly metabolized by CYP2C19.
Normal Metabolizer Standard dosing is expected to work for you. Initiate therapy with recommended starting dose.
Intermediate Metabolizer Your body may break down the drug more slowly, increasing side effects. Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers.
Likely Intermediate Metabolizer Your body may break down the drug more slowly, so you might need a lower or slower-adjusted dose. Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers.
Likely Poor Metabolizer You process the drug very slowly, which may raise side effects. Consider a clinically appropriate antidepressant not predominantly metabolized by CYP2C19. If escitalopram is clinically appropriate, consider a lower starting dose, slower titration schedule, and 50% reduction of the standard maintenance dose compared with normal metabolizers.
Poor Metabolizer You break down the drug very slowly, increasing risk of side effects. Consider a clinically appropriate antidepressant not predominantly metabolized by CYP2C19. If escitalopram is clinically appropriate, consider a lower starting dose, slower titration schedule, and 50% reduction of the standard maintenance dose compared with normal metabolizers.
Indeterminate The impact of your genotype on response to this drug is unknown. Initiate therapy with recommended starting dose.
Not available The impact of your genotype on response to this drug is unknown. Initiate therapy with recommended starting dose.

Alternative Treatment Options

Examples of alternative treatment options from CPIC guidelines include selecting an antidepressant not predominantly metabolized by CYP2C19—such as sertraline, mirtazapine, or bupropion—depending on clinical judgment. These are provided as examples and not direct medical advice.

Sources and References

Disclaimer: This document is for informational purposes only and is not a substitute for medical advice. Clinical decisions should be made by a qualified healthcare professional.

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