Imagine a treatment that could end depression in a single day with little to no side effects. It might sound like the inflated claims of a late-night infomercial, but researchers at the University of Maryland have reason to believe such treatment will one day be reality thanks to their identification of compounds that appear to restore the brain’s ability to feel pleasure within 24 hours. The researchers, led by Scott Thompson, PhD, a professor at the University of Maryland School of Medicine and the chair of its department of physiology, made the discovery in studies using rats, which share many structural and functional similarities to humans. The team hopes the results will translate. “These compounds produced the most dramatic effects in animal studies that we could have hoped for,” Dr. Thompson said in a university press release after the study was published in April 2015 in the journal Neuropsychopharmacology. “It will now be tremendously exciting to find out whether they produce similar effects in depressed patients. If these compounds can quickly provide relief of the symptoms of human depression, such as suicidal thinking, it could revolutionize the way patients are treated.”
Changing the Brain’s Messaging
Currently, most patients with mood disorders are treated with antidepressants that are intended to increase the levels of the neurotransmitter serotonin in the brain. But these drugs have limitations: They don’t work for everyone, and when they do, they typically take three to eight weeks to kick in. That can be a dangerous delay for those struggling with suicidal thoughts. The University of Maryland researchers decided to approach the problem from another direction. Rather than attempting to boost mood by elevating serotonin, they looked at another neurotransmitter, an inhibitory compound called GABA. If they could get GABA to reduce its inhibitory messaging, they theorized, the brain might return to the proper balance between excitatory and inhibitory communication — the hallmark of healthy mood. They identified a class of compounds called GABA-NAMs, which not only did the trick but were able to work only in the parts of the brain related to mood. This ability meant more precision and fewer side effects. In the study, rats were first stressed in ways that caused them to act as depressed humans do. Administering GABA-NAMs quickly boosted the strength of excitatory communication in the brain, successfully reversing a key symptom of depression — anhedonia, or the inability to feel pleasure. Most startling to the study team, the improvement was seen within 24 hours. No effect was noted in rats that weren’t depressed, providing more proof that unintended side effects are unlikely.
Hope for a New Class of Antidepressants
The findings are promising for people struggling with depression. The Anxiety and Depression Association of American estimates that 3% to 5% of the population suffers from major depression — which interferes with the ability to work, eat or sleep — at any given time. “Our results open up a whole new class of potential antidepressant medications,” Dr. Thompson said. “We have evidence that these compounds can relieve the devastating symptoms of depression in less than one day, and can do so in a way that limits some of the key disadvantages of current approaches.”