Why do commonly prescribed drugs help some patients but not others?
Antidepressants are among the most commonly prescribed drugs in America. More than one in 10 people—age 12 and over—take medications such as Prozac, Zoloft, Wellbutrin, and Effexor. The prevalence of antidepressants is felt across the culture, inspiring books such as Listening to Prozac and Coming of Age on Zoloft and fueling debates across medical and patient communities about how best to treat depression.
One issue facing those who decide to take an antidepressant is simply finding the right one—a potentially challenging and confounding experience. “Each of these drugs only works on a subset of patients,” says Benjamin Samuels, a professor in the Department of Psychology in the School of Arts and Sciences. “And there is no way to predict who is going to respond to which drug. Most psychiatrists simply try one drug first, and if that doesn’t work, they prescribe drug number two and then drug number three.
Samuels, a neuroscientist, would like to reduce or remove the element of guesswork for both patients and providers. His research explores the circuitry of the brain and how different mechanisms may trigger a response—or not—to widely used antidepressants such as selective serotonin reuptake inhibitors (SSRIs). By shedding light on the complex reactions in the brain, Samuels aims to build a body of knowledge to spur improved treatments as well as more accurate ways of predicting which drugs will work for which patients.
“We could eventually come up with totally new approaches to treating depression,” he says. “We could develop personalized treatment strategies that directly target circuits in each person’s brain that are responsible for their antidepressant response.”
Samuels recently received a five-year grant from the National Institute of Mental Health for a study entitled Molecular and Neural Circuitry Mechanisms Underlying Antidepressant Treatment Resistance. He notes that approximately 32 to 35 million adults in the United States experience an episode of major depression in their lifetime and only one-third experience a remission of symptoms following the first attempt at treatment.
Working in a lab on Busch Campus at Rutgers University–New Brunswick, his research team examines the area of the brain known as the dentate gyrus, which is part of the hippocampus and is thought to play a critical role in learning, memory, and emotion. In experiments with laboratory mice, Samuels and his team study the neural differences—such as the presence or absence of specific serotonin receptors and cellular signaling—between those that respond positively to antidepressants and those that do not.
One intriguing finding is the presence of activin, a peptide in the brain that gets released from one cell to another. “Generally, what we’ve seen is that there are more receptors for activin in the dentate gyrus of those responding to Prozac,” he said. “So in our experiment, we inject activin into the non-responders. And they start to look more like the responders.”
The team is also engaged in experiments that seek to identify biomarkers, or substances in the body, that would predict responses to antidepressants.
“By using biomarkers such as proteins, it may be possible to tell—before treatment is even started—how a patient may respond to a specific drug,” says Christine Yohn, a graduate student in Samuels’ lab.
Yohn and other students say they are drawn to the research because it reflects the ideal intersection of psychology and life sciences. “I’ve always wanted to pursue psychology, but my interest really was not in the clinical,” says senior Emma Diethorn, a cognitive neuroscience major. “This lab’s focus on the process and mechanisms of the antidepressant response is exactly what I’m interested in.”
Sophie Shifman, also a senior, agrees. She’s a cell biology and neuroscience major interested in medical or graduate school. “This lab is very hands-on,” she says. “We’re working everyday with the brain, learning how cells develop and proliferate, and I hope to apply what I have learned and possibly become a neurologist or psychiatrist.”
Samuels, who came to Rutgers in 2015, became interested in this research as a graduate student at Harvard University where he earned a Ph.D. in neurobiology.
“I’ve always been interested in how the brain controls behavior,” Samuels says. “When it comes to depression and anxiety, there are still so many unanswered questions, with so many potential benefits.”