By Kayt Sukel
Finding the right anti-depressant medication isn’t easy. When Allison first sought help with her depression, she thought a simple prescription would get her back to normal straightaway.
“The doctor prescribed one medication and, six weeks later, it was clear it wasn’t working. With the side effects, I actually felt worse than when I first came in. It was awful,” she says. “So we tried a second anti-depressant, which eventually did help, but we had to work with the dosage to even get that right. It ended up taking months to figure it all out—and it was really frustrating.”
Dr. Bradley Gaynes, M.D., M.P.H., says Allison’s experience isn’t uncommon. A practicing psychiatrist and mental health researcher at the University of North Carolina School of Medicine, Dr. Gaynes says that prescribing the right anti-depressant drug is a bit of a trial-and-error process.
“Many clinicians have a few drugs that they regularly use. They are very comfortable prescribing them and know the side effects pretty well—so that’s where they start,” he says. “Other doctors may look to newer drugs or try to prescribe based on a patient’s most distressing symptom. But there’s not usually a clear winner for which medication you should select for an individual patient.”
At the group level, Gaynes added, the rates of efficacy between different drugs are quite similar, but doctors have lacked insight into what patient will respond to what medication at the individual level. “If you treat 100 people with one drug, 50 people might get better. In another trial, with a different drug, 50 will also get better,” he said. “So the rates are the same—but we have had no way of knowing which of those 100 people are going to respond to what drug.”
In 2006, the National Institute of Mental Health (NIMH) launched the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study to help better understand the effectiveness of treatments for patients with major depression. They learned that it often takes two to three tries before a patient receives the medication that will put his or her depression into remission.
“What STAR*D and other clinical studies have shown us is that only about 30 percent of patients will get to recovery with the first drug you select,” Gaynes said. “If you try something new a second time, your chance of recovery is still at 30 percent. So after two efforts, you’ve roughly helped half those patients reach their treatment goals. If you go on for that third try, it gets tougher —now the rate drops to 15 percent. So even after three or four tries, you’ve still only helped about 70 percent of patients. It takes a lot of tries to get people where you want them—which is a return to a normal clinical state.”
The reasons for this varies from patient to patient. Some patients, like Allison, can’t handle the sometimes deleterious side effects of certain drugs. Others may have co-morbid disorders like generalized anxiety disorder or substance abuse problems that make finding the right medication a challenge. But Gaynes argues that the truth of the matter is that depression is just a really heterogeneous disease.
“In some ways, depression is like cancer. There are lots of different types of cancers—and those different types will require different treatments,” he says. “The thing about cancer is that you can look at the pathology, the cell types, genetic markers and other information to help figure out the best treatment.”
When it comes to depression, doctors have lacked the same kind of lab tests or biomarkers to look at — until the advent of more recent tests like GeneSight, which helps healthcare providers take a personalized approach to prescribing medicine for patients. Using DNA gathered with a simple cheek swab, GeneSight analyzes a patient’s genes and provides individualized information to help healthcare providers select medications that better match their patient’s genes.
“That is where the field is moving—and it’s a really promising area that may help us do better in the future,” Gaynes said.