Clinical area · Psychiatry

Same antidepressant, same dose. Three different blood levels.

Most antidepressants are processed by CYP2D6 and CYP2C19. The physician sets the dose; the enzyme sets the blood level: side effects are expected in poor metabolizers, lack of effect in ultrarapid ones.

Prepared by the BIODECODE science team · Last updated: October 2026 · Based on CPIC, DPWG, FDA and peer-reviewed publications

In brief

  • Most antidepressants are processed in the liver by the CYP2D6 and CYP2C19 enzymes. How fast these enzymes work varies genetically from person to person.
  • So the same dose can cause side effects in one patient and do nothing in another. Because antidepressants take weeks to work, every wrong attempt costs significant time.
  • Pharmacogenomic testing guides the physician in choosing the first drug and dose. The aim is to shorten the trial-and-error process.

Key concepts

Blood level

The amount of drug in the blood. Too low and there is no effect; too high and side effects increase. The goal is the balance called the "therapeutic range".

Poor metabolizer

Someone who processes the drug slowly. The drug builds up and the risk of side effects rises.

Ultrarapid metabolizer

Someone who processes the drug very fast. Blood levels do not rise enough and the drug may not work.

Time to response

The full effect of antidepressants usually appears over several weeks. Every attempt with an ineffective drug delays recovery.

Why does the same dose give different results?

  1. The physician prescribes the standard dose

    The starting dose is chosen from a range known to be safe and effective for most patients.

  2. The enzyme sets the blood level

    The speed of CYP2D6 or CYP2C19 determines how long the drug stays in the blood.

  3. The result differs by person

    In a slow processor the drug accumulates and side effects appear; in a fast processor it never reaches therapeutic levels.

How does genotype affect antidepressant choice?

Metabolizer typeWhat happens?General guideline approach*
PoorThe drug accumulates; side-effect risk rises.A lower starting dose, or a drug processed by a different pathway, is considered.
IntermediateThe drug may build up somewhat.Standard start for most drugs; doses are increased more carefully.
NormalExpected blood level.Standard treatment.
UltrarapidBlood levels may stay low; the drug may not work.A drug processed by a different pathway is considered.

* General framework based on CPIC guidelines for SSRIs and tricyclic antidepressants. Recommendations vary by drug; the report gives a separate verdict for each.

Who is it relevant for?

  • People about to start an antidepressant for the first time
  • Patients who have not responded to more than one antidepressant
  • Patients who have had marked side effects on antidepressants
  • People taking several psychiatric and non-psychiatric drugs

Your physician decides whether the test is right for you.

Evidence

  • 90–95%

    Share of people carrying at least one actionable pharmacogenetic variant

    PREPARE · Swen et al., The Lancet 2023
  • 30% ↓

    Reduction in clinically relevant adverse drug reactions with genotype-guided prescribing using a 12-gene panel (open-label trial)

    PREPARE · Swen et al., The Lancet 2023
  • ~7,000

    Patients from 7 European countries in the PREPARE trial

    Same study
  • 70%

    Rate at which prescribers followed genotype-guided advice

    Same study

Related genes and drugs

GeneRoleRelated drugsSource
CYP2C19Enzyme that processes citalopram, escitalopram and sertralineCitalopram, escitalopram, sertralineCPIC
CYP2B6Enzyme that contributes to sertraline processingSertralineCPIC
CYP2D6Enzyme that processes tricyclic antidepressants and atomoxetineAmitriptyline and other tricyclics, atomoxetineCPIC
HLA-B*15:02 · HLA-A*31:01Alleles that set the risk of severe skin reactions with carbamazepine and oxcarbazepineCarbamazepine, oxcarbazepineCPIC

What you will see in the BIODECODE report

  • 2 key enzymes

    CYP2D6 and CYP2C19 phenotypes; read-based phasing and copy-number checks for CYP2D6.

  • Drug by drug

    Antidepressants and antipsychotics on separate cards; CPIC and DPWG side by side where they differ.

  • Phenoconversion

    Cases where a concomitant drug may change a genotype-based verdict are flagged.

  • Psychiatry section

    Every card shows the verdict, source gene and full guideline text.

Sample report (PDF)

Good to know

  • Genotype explains only part of antidepressant response. Diagnosis, severity, adherence and life circumstances also matter.
  • Some antidepressants, such as fluoxetine and paroxetine, suppress CYP2D6. This can make the patient behave differently from what their genotype predicts (phenoconversion).
  • The PREPARE trial used an open-label design; the size of the effect remains under scientific debate.

Frequently asked questions

Will the test tell me exactly which antidepressant suits me?

No. Genotype helps predict blood levels and the likelihood of side effects; drug selection is made together with diagnosis, history and the physician's judgement.

My current medicine is not working; would testing help?

Not seeing the expected effect of a medicine is one of the most common reasons for testing. Ask your physician.

Can I stop my medicine based on my test result?

No. Stopping antidepressants suddenly can cause withdrawal symptoms and worsen the illness. Every change should be made under medical supervision.

References

  1. Swen JJ et al. A 12-gene pharmacogenetic panel to prevent adverse drug reactions (PREPARE). Lancet. 2023.
  2. Bousman CA et al. CPIC guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4 and HTR2A genotypes and serotonin reuptake inhibitor antidepressants. Clin Pharmacol Ther. 2023.
  3. Hicks JK et al. CPIC guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2017.
  4. Phillips EJ et al. CPIC guideline for HLA genotype and use of carbamazepine and oxcarbazepine: 2017 update. Clin Pharmacol Ther. 2018.

This page is for information only; diagnosis and treatment decisions belong to your physician. Never stop or change a medicine on your own.

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