Review of Genetic Biomarkers Improves Depression Therapy

Unfortunately, prescription of an effective anti-depressant medication is often a hit and miss proposition as an individual’s genetic make-up often determines if the medication works or not.

New research suggests checking a person’s genetic profile before prescribing an anti-depressant medication can help with the selection of the most effective medication.

The study finds that the failure of the current generation of antidepressant medications — selective serotonin reuptake inhibitors (SSRIs) occur because of genetic variations within the gene that encodes the CYP2C19 enzyme.

Researchers assessed the effectiveness of the SSRI escitalopram (Lexapro) and discovered variants in this gene results in extreme differences in the levels of escitalopram within a person’s blood profile — often limiting effectiveness.

Accordingly, prescribing the dose of escitalopram based on a patient’s specific genetic constitution would greatly improve therapeutic outcomes. The study, conducted at Karolinska Institutet in Sweden in association with researchers at Diakonhjemmet Hospital in Oslo, Norway, appears in the American Journal of Psychiatry.

Pharmaceutical treatment of depression commonly makes use of selective serotonin reuptake inhibitors (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 a recent 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.

Overall, one third of the 2,087 study participants achieved escitalopram blood levels that were either too high or too low.

Interestingly, 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,” says Professor Magnus Ingelman-Sundberg 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.”

Source: Karolinska Institutet