New research indicates that a more personalized approach to antidepressants could become a reality. Scientists at Tel Aviv University have discovered a gene that could indicate which type of medication might be effective for individual patients.
Their research focused on a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). SSRIs are the most commonly prescribed type of antidepressant today and are effective for approximately 60 percent of the population that takes them, but the process by which an effective drug is identified currently consists largely of trial and error.
SSRIs can take anywhere from three to eight weeks to become effective. Some patients have to try multiple SSRIs, enduring numerous side effects, before finding the best medication for them personally. This can be a long and frustrating process for the patient suffering with depression and may be frustrating for the doctors prescribing these medications as well.
This new research could aid in identifying which class of antidepressants would be most effective for an individual through the use of genetic testing. The scientists hope that their work will ultimately lead to a blood test that could identify not only if SSRIs in general would be effective for an individual, but if so, which specific SSRI might work best for that person. If SSRIs could be ruled out as a possibility for an individual doctors would be able to more quickly move on to other varieties of antidepressants such as tricyclics or monoamine oxidase inhibitors (MAOIs).
Dr. David Gurwitz, one of the researchers involved with this work said of the study “(w)e are working to move the treatment of depression from a trial-and-error approach to a best-fit, personalized regimen.” His team hopes to make the dream of personalized antidepressants a reality.
Working at a cellular level, the scientists have determined that a gene called CHL1 could hold the key as to whether a person will be responsive to SSRIs at all. This conclusion was reached after paroxetine, an SSRI marketed as ‘Paxil’, was applied to 80 cell lines. “CHL1 was produced in lower levels in the most responsive cell lines and higher levels in the least responsive cell lines.”
Their research suggests that it is this specific gene that may be able to predict whether a person will respond to SSRIs at all, and further which SSRI might be most effective.
In addition, the scientists wanted to understand the reason behind why the CHL1 levels could potentially predict responsiveness to SSRIs. In order to make that determination they applied paroxetine to human cells for a period of three weeks, which is generally considered to be the least amount of time it takes for an SSRI to become effective. They found that the paroxetine led to an increased production of another gene, ITGB3, the protein product of which is thought to interact with CHL1 in the development of new neurons and synapses.
This information may provide some explanation for the cause of delayed effectiveness of antidepressants in the SSRI family, as it takes weeks for new neurons and synapses to develop and result in the repair of dysfunctional signals to parts of the brain that control mood.
The researchers caution that they are in the early stages of their work and say that they now intend to work to replicate these results in animals and humans.
Depression affects approximately one in 10 American adults and approximately three percent of teens. Women are more than 70 percent more likely than men to suffer from depression. Other risk factors for depression include being a minority, being unemployed and having less than a high school education. The average age of onset for depression is 32 with peak ages for the disorder being between 45 and 64.
Symptoms of depression can be debilitating and interfere with a person’s ability to work, eat, sleep, study or enjoy activities they once found joy in. Although there are multiple varieties of depression, it is typically marked across the board by feelings of persistent sadness, hopelessness, worthlessness, guilt and/or shame. Irritability, fatigue and decreased energy are also hallmarks of the disorder. Changes in appetite, sleep and sexual habits are common as well. Physical pain and digestive issues may be present and depression may interact with other illnesses. Suicidal thoughts or attempts mark the most serious cases.
Elizabeth Wurtzel famously wrote of depression in her best-selling memoir Prozac Nation “A human being can survive almost anything, as long as she sees the end in sight. But depression is so insidious, and it compounds daily, that it’s impossible to ever see the end.”
Treatment for depression generally involves a combination of medication and talk therapy, though alternative treatments exist as well. The fact that medication is considered one of the first lines of treatment for depression makes this work all the more promising. For the millions suffering and the millions more at risk, this new research offers hope that a personalized approach to antidepressants and the possibility of faster recovery, may become a reality.
By Michele Wessel