In order to individualize drug therapy, researchers have been investigating potential genetic biomarkers that might help predict an individual’s response to medications. Now a new study finds that certain genetic variations may help determine whether selective serotonin reuptake inhibitors (SSRIs) will be effective in people with depression.
The findings, published in the The American Journal of Psychiatry, show that variations within the gene responsible for the metabolism of escitalopram (the SSRI Lexapro) can result in extreme differences in the levels of the drug achieved in patients, often either too low or too high. Therefore, prescribing the dose of escitalopram based on a patient’s specific genetic constitution would greatly improve therapeutic outcomes in these cases.
The study, which involved 2,087 patients, was conducted at Karolinska Institutet in Sweden in association with researchers at Diakonhjemmet Hospital in Oslo, Norway.
SSRIs are one of the most commonly prescribed pharmaceutical treatments for depression with escitalopram being the most frequently administered clinically. However, escitalopram therapy is currently limited by the fact that many patients do not respond well to the drug. In fact, some people develop adverse reactions requiring discontinuation of treatment.
During the study, researchers discovered that variations in the gene encoding the enzyme responsible for escitalopram metabolism (CYP2C19) plays a very important role. Patients with a variant of the gene promoting increased enzyme expression had blood levels of escitalopram too low to impact the depression symptoms, while patients with a defective CYP2C19 gene reached drug levels which were too high.
Overall, one-third of the study participants achieved escitalopram blood levels that were either too high or too low.
Importantly, the researchers found that 30 percent of the patients carrying gene variants causing excessive or inadequate enzyme levels switched to other drugs within one year, in contrast with only 10 to 12 percent of patients carrying the common gene.
“Our study shows that genotyping of CYP2C19 could be of considerable clinical value in individualizing doses of escitalopram so that a better all-round antidepressive effect could be achieved for the patients,” said Professor Magnus Ingelman-Sundberg at Karolinska Institutet’s Department of Physiology and Pharmacology, who led the study together with Professor Espen Molden.
“Because CYP2C19 is involved in the metabolism of many different SSRIs, the finding is also applicable to other types of antidepressants.”
Major depression is among the most common and severe health problems in the world. At least eight to 10 percent of the U.S. population suffers from major depression at any given time. It is characterized by a persistently depressed mood and loss of interest in activities.
Source: Karolinska Institutet