"Imagine that you are depressed and see a psychiatrist who explains that you have clinical depression and would benefit from an antidepressant. So far, so good. But then the doctor tells you there is a 60 percent chance that you’ll feel better with this antidepressant and that it could take as long as four to six weeks to find out, during which time you’ll probably have some side effects from the drug.
I have just described the state-of-the-art pharmacologic treatment of major depression in 2007. Don’t get me wrong; we have very effective and safe treatments for a broad array of psychiatric disorders. But in everyday clinical practice, we have little ability to predict which specific treatment will work best for you.
Laura is a case in point. A successful management consultant in her late 30s, she sought help for lifelong depression. Her treatment began with four weeks of the antidepressant Lexapro, a selective serotonin reuptake inhibitor, or S.S.R.I., without any effect. Next, I switched her to Zoloft, another S.S.R.I., since the chance of response to another member of the same drug family is about 60 percent. Again, no response. Then we moved on to Wellbutrin, an entirely different type of antidepressant, but this didn’t work either. Laura was now ready to call it quits, and who could blame her?
After nearly three months, I had still not found an effective treatment for her. Then she came in one day and said her father had recently revealed that he had been depressed and had done well on Prozac, another S.S.R.I., and she wondered if she could try it. Within three weeks, she felt markedly better, and the symptoms of her depression began to melt away.
Instead of the hit-or-miss approach I had to use with Laura, it will soon be possible for a psychiatrist to biologically personalize treatments. With a simple blood test, the doctor will be able to characterize a patient’s unique genetic profile, determining what biological type of depression the patient has and which antidepressant is likely to work best.
Scientists have identified genetic variations that affect specific neurotransmitter functions, which could explain why some patients respond to some drugs but not to others. For example, some depressed patients who have abnormally low levels of serotonin respond to S.S.R.I.’s, which relieve depression, in part, by flooding the brain with serotonin. Other depressed patients may have an abnormality in other neurotransmitters that regulate mood, like norepinephrine or dopamine, and may not respond to S.S.R.I.’s.
In a report last October in the journal Science, Dr. Francis Lee, a colleague of mine at Weill Cornell Medical College, identified a genetic mutation that could potentially predict patients’ responses to an entire class of antidepressants."