Why some people respond better than others to antidepressant citalopram

Washington, July 15 : Mayo Clinic scientists say that variations in the serotonin transporter gene may help understand why some people respond better than others to treatment with an antidepressant medication called citalopram (Celexa).

Writing about their latest study in the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, the researchers revealed that they examined the serotonin transporter gene (SLC6A4) in 1,914 subjects.

They say that two variations in the gene were found to have a direct bearing on how individuals might respond to citalopram.

According to the researchers, SLC6A4 produces a protein that plays an important role in achieving an antidepressant response.

During the study, the influence of variations in SLC6A4 in response to citalopram treatment was evaluated in white, black and Hispanic patients.

The research group observed that white patients have two distinct gene variations were more likely to experience remission of symptoms associated with major depression, while no associations between the two variations and remission were found in black or Hispanic patients.

"The findings of this study represent another step in advancing individualized medicine for psychiatric patients," said Dr. David Mrazek, chair of the Mayo Clinic Department of Psychiatry and Psychology and the study's senior author.

It is believes that pharmacogenetics-the study of how people's genetic makeup affects their response to medications-may improve patient outcomes by matching patients with the right drug from the start, instead of enduring the arduous process of trial and error.

"Patients want to feel better as quickly as possible so the idea of trying one drug after another until you find one that works can be discouraging. The development of pharmacogenetic testing will help increase the likelihood of selecting an effective drug the first time," Dr. Mrazek said.

He revealed that his team's study was based on the analysis of a data sample from the Sequenced Treatment Alternatives to Relieve Depression Study (Star-D), a National Institute of Mental Health seven-year study that analysed treatment for adult patients diagnosed with major depression.

He said that his team genotyped DNA from 1,914 subjects from the Star-D study for the purpose of their research.

He revealed that the final analysis included 1,503 subjects, including 1,074 whites, 233 blacks and 196 Hispanics.

Dr. Mrazek said that his team was conducting further studies to improve pharmacogenetic testing.

"In the years to come we will be exploring many more genes that influence medication response. In addition to looking at the serotonin transporter gene, we will be looking at serotonin receptor genes and genes that produce the enzymes that metabolize citalopram. By looking at all the genes together we will have a better ability to predict which patients will respond to each antidepressant medication," he said.

He said that examining how other genes predict response to treatment with citalopram, and how variations within SLC6A4 might influence how other medications work are some of the next steps in this field.

"Each step is a step toward greater accuracy in prescribing the right medication for each patient. First, we started with trial and error - which feels like flipping a coin to select a medication. The Holy Grail would be to be able to consider the implications of variations in many genes. Ultimately, we hope to be able to determine with great accuracy which patients will respond to specific antidepressants and which patients will almost certainly not respond," Dr. Mrazek said.

The researcher revealed that less than 50 percent of patients treated in clinical trials experience complete remission of their symptoms, despite the wide use of antidepressant medications.

However, with pharmacogenetic testing, patient outcomes could improve because prescribed medications would be based on a patient's genetic makeup.

"Not all patients respond on the first try. Many patients require two or three trials of medications before we find one that works for them. Our goal is to develop genetic tests that will be easy to administer and will give us results that indicate whether a patient will respond or not," Dr. Mrazek said.

He said that pharmacogenetic testing, which could help determine which patients will respond to citalopram, was available.

He suggested that people who were still sceptical should talk to the their doctors about pharmacogenetics.

"I would predict that within two years there will be more extensive tests available that will be more accurate than tests that focus on one gene. We already know there are half a dozen genes that can provide clues in selecting the right medication for patients," Dr. Mrazek said.

ANI