PALO ALTO, Calif., Aug. 05, 2026 (GLOBE NEWSWIRE) -- 23andMe Research Institute, a nonprofit research organization dedicated to advancing science for the public good, announced the publication of a study demonstrating the impact of genetic variation on risk of specific side effects related to the use of three common selective serotonin reuptake inhibitors (SSRIs) antidepressants, escitalopram (Lexapro®), citalopram (Celexa®), and sertraline (Zoloft®). The CYP2C19 gene was already known to be involved in the processing of these drugs. This large-scale study is the first to link genetic variation in CYP2C19 to a person's risk of specific SSRI side effects such as sexual dysfunction and trouble sleeping.
Published today in The Pharmacogenomics Journal, the study investigates the genetic basis of variability in side effects with common SSRI antidepressants. Researchers at the 23andMe Research Institute examined data from more than 114,000 individuals who have used this class of antidepressants and responded to a survey about the effectiveness of the medication(s) and what side effects they experienced. They looked for differences in effectiveness, side effects and reasons for discontinuation when relevant based on the individual’s CYP2C19 genetic variants (i.e. metabolizer status). The findings provide evidence that variation in the CYP2C19 gene is associated with variations in response to SSRI therapies. Specifically, the study included the following key findings:
- Participants whose CYP2C19 variant results in slower metabolism of SSRIs have significantly increased risk of very specific side effects like tremors, sleep issues and sexual dysfunction.
- Slower CYP2C19 metabolizers were more likely to discontinue their SSRI medication due to side effects.
- The study gives 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.
Finding the right antidepressant is often a long, frustrating process. Fewer than half of people respond to the first SSRI 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.
Study participants were sorted into categories of metabolizer types, ranging from poor (slowest) to ultrarapid (fastest) based on which genetic variants they had. For individuals with the version of the CYP2C19 enzyme that works more slowly, the drug lingers in their system at higher concentrations, which raises the 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 and not just side effects as a general category. 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 metabolizers quitting their medication altogether due to side effects (depending on which drug they took, between 25.7% and 29.7% of poor metabolizers stopped compared with 20.2% to 21.6% of ultrarapid metabolizers).
Finally, the study highlights why diversity in genetic research matters. Genetic ancestry impacts how common these variants are in a given population. Roughly 17.8% of East Asian-ancestry participants were poor metabolizers, compared with about 2.3% of European-ancestry participants.
“Because 23andMe has such a massive community of people choosing to participate in research, we were able to pair genetic data with real, personal experiences on these medications,” noted Dr. Ryanne Wu, M.D., one of the lead authors of the paper and director of genomic medicine at the 23andMe Research Institute. “Earlier studies were too small to spot these patterns and 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.”
For those who are considering an SSRI, or those who have struggled with SSRI side effects in the past, genetics may offer important insights. 23andMe Premium Ancestry + Health members can view their CYP2C19 Drug Metabolism report* and talk with a healthcare professional about how their status may affect their response to certain medications including SSRIs. Giving them one more data point to help find a treatment that fits.
About 23andMe Research Institute
23andMe Research Institute is a new nonprofit 501(c)(3) research organization that enables people everywhere to access their genetic information, learn about themselves, and participate in large-scale research for public good. The Institute unites people with the common goal of improving health and deepening our understanding of DNA, the code of life.
Media Contact:
Aushawna Collins
23andMe Research Institute
aushawnac@23andme.com
*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.
