Genetic Makeup May Predict Antidepressant Success

By: Diana Barnes-Brown for Body1

A report published in the October 4 issue of the Journal of the American Medical Association (JAMA) shows that there is a connection between patients’ genetic variations and whether antidepressants are effective.

Take Action

Depression is a common and treatable disease. If you or a loved one notice several of the following symptoms for two weeks or more, call your physician. He or she can work with you to determine the next steps. Feeling down, sad, empty or anxious with no known cause Feeling hopeless or pessimistic Feeling guilty, powerless, or worthless Loss of interest in activities that were at one time enjoyable Inability to complete simply daily tasks, for example bathing regularly or basic housekeeping Loss of interest in sex Thoughts of self-harm, death, or suicide; attempts at self-harm or suicide Appetite and/or weight changes Changes in sleep patterns such as difficulty sleeping or getting out of bed at normal hours Restless or irritable mood

Typically, physicians’ first tries at treating major depression are successful only about 60 percent of the time. In about 40 percent of cases, it is necessary to continue searching for a treatment that works. By improving the ability to predict the response to a certain drug based on genetic factors, specialists hoping to find successful drug therapies for depression can be more accurate when the first prescription is written. Consequently, patients will see results more quickly. This process is actually called pharmacogenetics – or the study of the relationship between genetic makeup and drug responsiveness.

The new study was led by Hyeran Kim, MD, of the Samsung Medical Center of the Sungkyunkwan University School of Medicine, in Seoul, Korea, and conducted in cooperation with United States researcher Bernard J. Carroll, MB, PhD, of the Pacific Behavioral Research Foundation in Carmel, California. The research team looked at variations in the serotonin transporter gene known as 5-HTT and a norepinephrine transmitter known as NET G1287A, and whether there was a strong correlation between the presence of certain variations and the success of antidepressant treatment.

The aim of the study was to examine the correlation between two classes of antidepressant drugs: selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs). The Seoul-based research team worked with a group of 241 Korean patients suffering from major depression. One hundred and thirty-six of the patients received SSRI treatment with either fluoxetine or sertraline for six weeks, while 105 received the NRI nortriptyline for six weeks. After the six-week treatment period, all were re-evaluated for changes in their psychological health. The patients had all experienced the onset of major depression in their early- to mid-fifties.

Patients with a genetic variation called NET G1287A responded much better to NRI treatment than SSRI treatment, with respective response rates of 83.3 percent and 58.7 percent. The researchers also found that there was some variation between Asian and Caucasian patients when it came to which gene variations correlated with the success of a particular antidepressant.

“Our data confirm a relationship between SSRI response and 5-HTT polymorphisms, and establish an association between NRI response and the NET G1287A polymorphism,” wrote the authors. “The results of this study need to be confirmed in other populations, using selective NRIs other than nortriptyline. Additional studies in younger populations with depression are also needed,” they added, but “confirmation of these preliminary findings would permit refined pharmacogenetic selection of antidepressant treatment.”

Depression is a psychological disorder that impacts millions worldwide. While this study looked at one particular age group in one particular region of the world, it represents a significant step towards establishing a clear relationship between a patient’s genetics and the success rate of an antidepressant. It would indeed change the face of depression treatment.

Last updated: 09-Nov-06