New method shows promise in treating antidepressant-resistant depression
A new study by University of Florida researchers could help reveal methods to treat depression when traditional medications aren’t working.
Depression affects about 121 million people worldwide, with about 10 percent of all cases involving people who don’t respond to antidepressants, according to an estimate by the U.S. Food and Drug Administration.
To uncover solutions to this problem, UF researchers studied two types of rat models, including one that is particularly sensitive to stress and highly resistant to antidepressant treatments. Researchers suspected that the stress-prone rats’ brains might have greater amounts of a protein that may play a role in depression, said Darragh P. Devine, Ph.D., the study’s lead author and a professor of behavioral and cognitive neuroscience in the UF College of Liberal Arts and Sciences department of psychology and the College of Medicine department of neuroscience. The study was published in the April edition of the journal Pharmacology, Biochemistry and Behavior.
The stress-sensitive rats that were exposed to chronic and acute stress had significantly higher levels of the protein, organic cation transporter-3 or OCT3, in the hippocampus, a part of the brain that plays a role in depression. Researchers believe OCT3 plays a role in chemical processes within the brain that can lead to depression or make it linger.
Next, the researchers looked for a way to create an antidepressant effect in the rat models. To do that, they tested a drug known as decynium-22, or D22. The drug had shown some antidepressant properties in an earlier study by other researchers involving a specially bred mouse model. Devine said those results were interesting, and wanted to know if D22 could work in a model of heightened stress responsiveness and resistance to antidepressant medication.
“It led us to the basic hypothesis that the stress-vulnerable rats might have a heightened response to D22. And that’s what we found,” Devine said.
As expected, the D22 created an antidepressant effect in the rat model by blocking the protein suspected of playing a role in depression. Devine’s research is believed to be the first time that D22 was found to have an antidepressant effect in the Wistar-Kyoto rat model.
It’s encouraging that the treatment worked selectively in a rat model that doesn’t respond to conventional depression treatments, Devine said. Although it’s too early to know whether a treatment that works on an animal model would help human patients, Devine said it shows promise as a first study.
Regulating brain chemistry is just one part of treating a condition as complex as depression, Devine said. Sometimes, a person’s immediate environment can play a big role in how soon — or if — he or she bounces back from depression, he added. Other experts and studies have cited stress, medical problems, genetic vulnerability and faulty mood regulation as possible causes of depression.
“So if you talk about treating depression, you can’t talk about curing things just with drugs,” he said.
The potential therapy discovered in his lab is one step toward a possible treatment for depression for those who don’t respond to conventional antidepressants alone, Devine said. Whether it could ultimately work as a primary treatment for depression or be used in combination with antidepressant medications hasn’t been determined, he said.