Sertraline (sold as Zoloft) is an SSRI antidepressant. It's FDA-approved for major depressive disorder, OCD, panic disorder, PTSD, social anxiety disorder, and premenstrual dysphoric disorder (PMDD).
SSRIs work by blocking the reabsorption of serotonin in the brain, leaving more of it available between nerve cells. That mechanism is the basis for their effect on mood and anxiety, though the full picture of why SSRIs help is still actively studied.
Two liver enzymes break sertraline down: CYP2C19 (the main one) and CYP2B6. Both are part of the cytochrome P450 family, which handles a large share of common medications.
If your version of either enzyme runs fast, sertraline can clear before it has a chance to work, and you may end up at sub-therapeutic levels on a standard dose. If your version runs slow, the drug accumulates and side effects come along with it.
Your CYP2C19 and CYP2B6 phenotype changes how much sertraline ends up in your bloodstream at a given dose. Ultrarapid and rapid metabolizers may not reach therapeutic levels at all on standard dosing. Intermediate and poor metabolizers tend to accumulate higher concentrations, which raises the chance of nausea, sexual side effects, and other tolerability issues. Knowing the phenotype before prescribing lets the dose match the person, instead of finding out after several weeks of trial.
The following dosing guidelines are based on CPIC recommendations for sertraline and take into account CYP2C19 and CYP2B6 metabolizer status.
| Phenotype | Clinical Consequence | Guideline Recommendation |
|---|---|---|
| Ultrarapid Metabolizer | Your body processes this drug slightly faster than average, but no dose change is needed. | Initiate therapy with recommended starting dose. |
| Rapid Metabolizer | Your body processes this drug slightly faster than average, but no dose change is needed. | Initiate therapy with recommended starting dose. |
| Normal Metabolizer | You can use the normal recommended dose for this medication. | Initiate therapy with recommended starting dose. |
| Intermediate Metabolizer | Your body processes this drug more slowly, so doctors may adjust the dose more carefully. | Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose. |
| Likely Intermediate Metabolizer | Your body processes this drug more slowly, so doctors may adjust the dose more carefully. | Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose. |
| Poor Metabolizer | Your body processes this drug much more slowly, so you may need a lower dose to avoid side effects. | Consider a lower starting dose, slower titration, and 50% reduction of maintenance dose or select an alternative not predominantly metabolized by CYP2C19. |
| Likely Poor Metabolizer | Your body processes this drug much more slowly, so you may need a lower dose to avoid side effects. | Consider a lower starting dose, slower titration, and 50% reduction of maintenance dose or select an alternative not predominantly metabolized by CYP2C19. |
| 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. |
| Phenotype | Clinical Consequence | Guideline Recommendation |
|---|---|---|
| Ultrarapid Metabolizer | Your body processes this drug a bit faster, but no dose change is usually needed. | Initiate therapy with recommended starting dose. |
| Rapid Metabolizer | Your body processes this drug a bit faster, but no dose change is usually needed. | Initiate therapy with recommended starting dose. |
| Normal Metabolizer | You can use the normal recommended dose for this medication. | Initiate therapy with recommended starting dose. |
| Intermediate Metabolizer | Your body processes this drug more slowly, so your doctor may adjust the dose more carefully. | Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose. |
| Poor Metabolizer | Your body processes this drug much more slowly, so you may need a lower dose to avoid side effects. | Consider a lower starting dose, slower titration, and 25% reduction of maintenance dose or select an alternative not predominantly metabolized by CYP2B6. |
| Indeterminate | The impact of your genotype on response to this drug is unknown. | Initiate therapy with recommended starting dose. |
For patients who are poor metabolizers of CYP2C19 or CYP2B6, CPIC guidelines suggest considering an antidepressant not primarily metabolized by these enzymes. Examples may include fluoxetine or paroxetine for CYP2C19 poor metabolizers, and bupropion or mirtazapine for CYP2B6 poor metabolizers. These are provided as examples from guidelines, not as direct medical advice.
Gene2Rx uses the same CPIC and FDA guidelines as GeneSight, covers more medications, costs $5-$49 instead of several hundred, and works with the 23andMe or AncestryDNA data you may already have. See the full side-by-side comparison before ordering.
See the full list of drugs affected by each gene:
See how your genetics affect each product Sertraline shows up in:
Learn more about how genetics may affect your response to Sertraline and related medications:
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