In a breakthrough, scientists have identified promising compounds that could successfully treat depression in less than 24 hours with minimal side effects.
Although the compounds have not yet been tested in people, they could offer significant advantages over current antidepressant medications.
"Our results open up a whole new class of potential antidepressant medications," said Scott Thompson, Professor and Chair of the Department of Physiology at the University of Maryland School of Medicine (UM SOM).
"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," said Thompson.
Currently, most people with depression take medications that increase levels of the neurochemical serotonin in the brain.
The most common of these drugs, such as Prozac and Lexapro, are selective serotonin reuptake inhibitors, or SSRIs.
SSRIs are effective in only a third of patients with depression. Even when these drugs work, they typically take between three and eight weeks to relieve symptoms.
As a result, patients often suffer for months before finding a medicine that makes them feel better.
This is not only emotionally excruciating; in the case of patients who are suicidal, it can be deadly. Better treatments for depression are clearly needed, researchers said.
Thompson and his team focused on another neurotransmitter besides serotonin, an inhibitory compound called GABA. Brain activity is determined by a balance of opposing excitatory and inhibitory communication between brain cells.
Researchers argue that in depression, excitatory messages in some brain regions are not strong enough.
As there is no safe way to directly strengthen excitatory communication, they examined a class of compounds that reduce the inhibitory messages sent via GABA. They predicted that these compounds would restore excitatory strength.
These compounds, called GABA-NAMs, minimise unwanted side effects because they are precise: they work only in the parts of the brain that are essential for mood.
The researchers tested the compounds in rats that were subjected to chronic mild stress that caused the animals to act in ways that resemble human depression.
Giving stressed rats GABA-NAMs successfully reversed experimental signs of a key symptom of depression, anhedonia, or the inability to feel pleasure.
Remarkably, the beneficial effects of the compounds appeared within 24 hours - much faster than the multiple weeks needed for SSRIs to produce the same effects.
"These compounds produced the most dramatic effects in animal studies that we could have hoped for," Thompson said.
The study was published in the journal Neuropsychopharmacology.