Genetic Analysis May Improve Depression Therapy

The failure of drugs such as selective serotonin reuptake inhibitors (SSRIs), used to treat depression, can be a result of genetic variations in patients. Variations within the gene that encodes the CYP2C19 enzyme results in extreme differences in the levels of escitalopram achieved in patients, according to a new study published online on January 12, 2018 in The American Journal of Psychiatry. Prescribing the dose of escitalopram (Lexapro) based on a patient's specific genetic constitution would greatly improve therapeutic outcomes. The study was conducted at Karolinska Institutet in Sweden in association with researchers at Diakonhjemmet Hospital in Oslo, Norway. The title of the article is “Impact of CYP2C19 Genotype on Escitalopram Exposure and Therapeutic Failure: A Retrospective Study Based on 2,087 Patients.” Pharmaceutical treatment of depression commonly makes use of selective SSRIs, of which escitalopram is the most frequently administered clinically. However, escitalopram therapy is currently limited by the fact that some patients do not respond well to the drug, while others develop adverse reactions requiring discontinuation of treatment. In order to individualize drug therapy, researchers are attempting to establish genetic biomarkers that can predict an individual's response to drugs. In the new study, it was discovered that variation in the gene encoding the enzyme responsible for escitalopram metabolism (CYP2C19) is very important in this respect. Individuals with a variant of the gene promoting increased enzyme expression had blood levels of escitalopram too low to impact the depression symptoms, whereas patients with a defective CYP2C19 gene reached drug levels which were too high.
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