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Fluvoxamine

Antidepressants - SSRI

Drug Overview

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) commonly prescribed under the brand name Luvox. It is an oral antidepressant designed to help regulate mood by increasing serotonin availability in the brain.

This medication is primarily indicated for obsessive-compulsive disorder (OCD) and is also used off-label for depression and certain anxiety disorders. Treatment aims to reduce compulsive behaviors and improve overall mood.

Fluvoxamine works by blocking the serotonin transporter (SERT), preventing serotonin from being reabsorbed into neurons and thereby enhancing serotonergic signaling.

Relevant Genes and Their Roles

The key gene affecting fluvoxamine metabolism is CYP2D6, which encodes an enzyme in the liver responsible for processing many medications. Variants in CYP2D6 produce different metabolizer phenotypes—ranging from poor to ultrarapid—based on how active the enzyme is.

These genetic differences can alter how quickly fluvoxamine is cleared from the body. Poor metabolizers have reduced enzyme activity leading to slower clearance and higher drug exposure, while ultrarapid metabolizers break down the drug more quickly, potentially reducing its effectiveness.

Impact of Genetics on Drug Response

CYP2D6 phenotype groups influence fluvoxamine exposure and risk profile: poor metabolizers may have increased drug levels and greater side‐effect risk, ultrarapid metabolizers may clear the drug too fast to achieve benefit, and intermediate or normal metabolizers fall between these extremes, guiding dose selection and monitoring.

Expected Clinical Effects of Genetic Variation

Genetic variations in CYP2D6 influence fluvoxamine processing, altering drug exposure and side effect risk as follows:

Ultrarapid Metabolizer

  • Effect on drug levels: Decreased drug levels due to rapid metabolism
  • Clinical consequence: Potential reduced efficacy and insufficient symptom control
  • Side effects: Lower incidence of common SSRI side effects (e.g., nausea); severity and frequency not well established

Normal Metabolizer

  • Effect on drug levels: Expected drug levels under standard dosing
  • Clinical consequence: Typical therapeutic response at recommended doses
  • Side effects: Common mild to moderate effects such as gastrointestinal upset or insomnia

Intermediate Metabolizer

  • Effect on drug levels: Slightly increased drug levels due to reduced metabolism
  • Clinical consequence: Increased risk of side effects without dose adjustment
  • Side effects: More frequent mild to moderate effects like nausea or drowsiness

Poor Metabolizer

  • Effect on drug levels: Markedly increased drug levels from greatly reduced metabolism
  • Clinical consequence: Heightened risk of adverse effects at standard doses
  • Side effects: More severe or frequent events (e.g., sedation, nausea, potential for serotonin syndrome)

Indeterminate/Not available

  • Effect on drug levels: Unknown
  • Clinical consequence: No specific guidance; follow standard dosing with clinical monitoring
  • Side effects: Unknown

Dosing Guidelines

The following dosing guidelines are based on the available guidelines for fluvoxamine from the CPIC.

CYP2D6 Dosing Guideline

Phenotype Clinical Consequence Guideline Recommendation
Ultrarapid Metabolizer No data available; impact on metabolism unknown No recommendation due to lack of evidence.
Normal Metabolizer Normal metabolism of fluvoxamine Initiate therapy with recommended starting dose.
Intermediate Metabolizer Reduced metabolism leads to higher plasma concentrations and increased side effect risk Initiate therapy with recommended starting dose.
Poor Metabolizer Greatly reduced metabolism leads to significantly higher plasma concentrations and increased side effect risk Consider a 25–50% lower starting dose and slower titration schedule or an alternative antidepressant not predominantly metabolized by CYP2D6.
Indeterminate / Not available Unknown impact; no CPIC guidance Initiate therapy with recommended starting dose.

Alternative Treatment Options

Examples from the CPIC guidelines: for CYP2D6 poor metabolizers, consider alternative antidepressants not predominantly metabolized by CYP2D6 such as sertraline or escitalopram. These are examples only and not a substitute for professional 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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