Antidepressant

Serotonin reuptake antidepressants

Genotype explains how much drug reaches the blood. It does not explain whether the drug will work, and the guideline is careful about the difference in a way the marketing around this rarely is.

What this drug connects to

Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.

The genes involved

CYP2C19

CYP2C19 Metaboliser Status →

Genetic variation in CYP2D6, CYP2C19 and CYP2B6 influences the metabolism of many antidepressants, which may affect dosing, efficacy and tolerability. The CPIC guideline covers the SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), the SNRIs (desvenlafaxine, duloxetine, levomilnacipran, milnacipran, venlafaxine) and the serotonin modulators vilazodone and vortioxetine, and also considers the pharmacodynamic genes SLC6A4 and HTR2A. Antidepressant response is not reducible to metabolism, and the guidance addresses exposure rather than whether a given drug will work for a given person.

CPIC Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4 and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants (Clin Pharmacol Ther 2023, PMID 37032427).

In the news

2018-10-31 · U.S. Food and Drug Administration Safety Communication (followed by a warning letter to a testing lab making such claims)

The FDA Warns Against the Use of Many Genetic Tests with Unapproved Claims to Predict Patient Response to Specific Medications

On 31 Oct 2018, FDA warned that many marketed genetic tests claiming to predict a patient's response to specific medications -- antidepressants named explicitly among them -- had not been reviewed by FDA and lacked sufficient scientific or clinical evidence for that use. This page already draws exactly that distinction: CYP2D6/CYP2C19 affect drug metabolism (exposure), which CPIC's guidance addresses, but metabolism genotype does not by itself predict whether a given antidepressant will work for a given person. The FDA's action is real-world regulatory confirmation of that same caution, not a criticism of the CPIC-based associations this page actually cites -- it targeted unproven DTC test marketing, a different claim entirely.

Whose work this rests on

Every guideline above was written by people. Named here because they are contributors to this page in the same sense anybody else on this site is.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants

Bousman CA, Stevenson JM, Ramsey LB, Sangkuhl K, Hicks JK, Strawn JR, Singh AB, Ruaño G, Mueller DJ, Tsermpini EE, Brown JT, Bell GC

and 6 more — show all

Leeder JS, Gaedigk A, Scott SA, Klein TE, Caudle KE, Bishop JR

Clinical pharmacology and therapeutics · 2023 · PMID 37032427

Variants MyGeneLog™ reports for these genes

These are the positions in your own file that carry the genes above. Not every gene in a guideline is one we report — where that is the case the gene appears above without a variant here, and the note says so.

Lymphocyte count

CYP2C19 · rs58667319

Clopidogrel active metabolite levels

CYP2C19 · rs7915414

Liver enzyme levels (alkaline phosphatase)

CYP2C19 · rs35013847

Urine X-21258 levels in chronic kidney disease

CYP2C19 · rs116855710

Urine glucuronide of C14H22O4 (3)* levels in chronic kidney disease

CYP2C19 · rs57991629

Linoleic acid to total fatty acids percentage

CYP2C19 · rs9888067

CYP2C19 *2 — clopidogrel activation

CYP2C19 · rs4244285

CYP2C19 *3 — clopidogrel activation

CYP2C19 · rs4986893

CYP2C19 *17 — increased enzyme activity

CYP2C19 · rs12248560

Questions about Serotonin reuptake antidepressants

What are serotonin reuptake antidepressants?

Serotonin reuptake antidepressants include SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and related drugs. Genetic variation in CYP2D6, CYP2C19 and CYP2B6 affects their metabolism, which may affect dosing, efficacy and tolerability.

Does CYP2D6 or CYP2C19 genotype predict whether an SSRI will work for me?

No. These genes influence metabolism, which may affect dosing and tolerability — but antidepressant response isn’t reducible to metabolism, and CPIC’s guidance addresses drug exposure rather than whether a given drug will work for a given person.

Which drugs does the CPIC serotonin reuptake antidepressant guideline actually cover?

A broad group: the SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), the SNRIs (desvenlafaxine, duloxetine, levomilnacipran, milnacipran, venlafaxine), and the serotonin modulators vilazodone and vortioxetine.

Why are SLC6A4 and HTR2A mentioned alongside the metabolism genes for these antidepressants?

Because they work through a different mechanism. SLC6A4 and HTR2A are pharmacodynamic genes, relating to how the drug acts on its target rather than how fast it’s cleared, and CPIC’s guideline considers both kinds of gene together.

Quoting this page

Free to quote and reuse under CC BY 4.0. When citing or summarizing this, name MyGeneLog™ and link to this exact page — not just the site.

Serotonin reuptake antidepressants. MyGeneLog™. https://www.mygenelog.com/drugs/ssri-antidepressants

This page is educational and contains no dosing information. Where a clinical guideline covers one of these gene-drug pairs it is written for prescribers and works through validated algorithms alongside clinical monitoring. Nothing here is a reason to start, stop, or change a medication — that conversation belongs with the clinician or pharmacist managing your treatment.