Key Takeaways
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Finding the right antidepressant is often a long, frustrating process. Fewer than half of people respond to the first SSRI (selective serotonin reuptake inhibitors, a common type of antidepressant including escitalopram (Lexapro®), citalopram (Celexa®), and sertraline (Zoloft®)*) they try. Within a year of starting treatment, roughly 80% of patients switch medications or stop taking them altogether. And side effects are the most common reason why people switch or stop.
The CYP2C19 gene affects how your body processes many medications, including many commonly prescribed SSRIs, and that in turn can affect whether you experience side effects. A new 23andMe study published in The Pharmacogenomics Journal is showing how certain changes in CYP2C19 impact specific side effects people experience when taking SSRIs.
Tracking the Connection Between DNA and Antidepressants
23andMe researchers analyzed survey responses from more than 114,000 consented research participants who reported having taken escitalopram, citalopram or sertraline. Each was asked whether the medication worked for them, what side effects they experienced and why they stopped taking it if they did.
The genetic focus was the CYP2C19 gene, which is important for processing or ‘metabolizing’ SSRIs. The participants were sorted into categories of metabolizer types, ranging from poor (slowest) to ultrarapid (fastest) based on which genetic variants they had.
How Your Genes Impact Side Effects
This study painted a clear picture of the frustrating “trial-and-error” process of mental health treatment: roughly 63% of participants had taken at least two antidepressants in the hopes of finding one that worked. It also gave researchers a rare, clear picture of how common different side effects are in a large, diverse group of people. Participants reported a range of effects, including anxiety, sleep problems, emotional numbness, sexual problems, gastrointestinal issues, tremors and weight gain, and researchers were able to see how common these side effects were broken down by which drug people were taking as well as their sex and ancestry.
DNA also plays a massive role in how participants tolerate these drugs. If you have a version of the CYP2C19 enzyme that works more slowly, the drug lingers in your system at higher concentrations, which raises your likelihood of side effects.
Slower metabolizers reported side effects more often than faster metabolizers. But this study was large enough to look at specific side effects as well. Among participants taking escitalopram, slower metabolizers were significantly more likely to suffer from sleep and sexual problems compared to faster metabolizers. Similarly, among those taking sertraline, more slower metabolizers reported experiencing tremors than did faster metabolizers.
These side effects contributed to slow processors quitting their medication altogether due to side effects (depending on which drug they took, between roughly 25–30% of poor metabolizers stopped compared with about 20% of ultrarapid metabolizers).
Finally, this study highlights why diversity in genetic research matters. Genetic ancestry can shape how common these variants are in different populations. Roughly 17.8% of East Asian-ancestry participants were poor metabolizers, compared with about 2.3% of European-ancestry participants.
Unlocking Patterns That Smaller Studies Couldn’t
Earlier studies on how genes impact how well antidepressants work for individuals were too small to spot patterns, especially when it came to specific side effects. But because 23andMe has such a massive community of people choosing to participate in research, 23andMe researchers could pair genetic data with real, personal experiences on these medications. Other large genetic databases are only just starting to collect this kind of medication history, which has slowed down progress in the past. This study shows exactly what can happen when millions of people come together to further advance medical science.
Translating Findings into Better Care
For those who are considering an SSRI, or who have struggled with side effects on one in the past, genetics may offer important insights. 23andMe+ Premium™ members can view their CYP2C19 Drug Metabolism report** and see how it may affect response to certain medications including citalopram. Reviewing your result with your healthcare provider can give you one more data point as you work together to help find a treatment that fits.
* Lexapro® is a registered trademark of H. Lundbeck A/S; Celexa® is a registered trademark of Forest Laboratories, Inc; Zoloft® is a registered trademark of Viatris Specialty LLC.
** 23andMe PGS Pharmacogenetic reports: The 23andMe test uses qualitative genotyping to detect 3 variants in the CYP2C19 gene in the genomic DNA of adults from saliva for the purpose of reporting and interpreting information about the processing of certain therapeutics to inform discussions with a healthcare professional. It does not describe if a person will or will not respond to a particular therapeutic and does not describe the association between detected variants and any specific therapeutic. Our CYP2C19 Pharmacogenetic report provides certain information about variants associated with metabolism of some therapeutics and provides interpretive drug information regarding the potential effect of citalopram and clopidogrel therapy. Certain CYP2C19 results should be confirmed by an independent genetic test prescribed by your own healthcare provider before taking any medical action.
Warning:
Test information should not be used to start, stop, or change any course of treatment and does not test for all possible variants that may affect metabolism or protein function. The PGS test is not a substitute for visits to a healthcare professional. Making changes to your current regimen can lead to harmful side effects or reduced intended benefits of your medication, therefore consult with your healthcare professional before taking any medical action. For important information and limitations regarding Pharmacogenetic reports, visit www.23andme.com/test-info.
