New Anti-depressant Compounds May Work Fast, Have Few Side Effects

New compounds that could effectively treat depression in less than 24 hours, while curtailing side effects, have been identified. The compounds, according to a new study by researchers at University of Maryland School of Medicine, could offer significant advantages over current antidepressant medications, even though they have not yet been tested in people.

Research leader Scott Thompson, PhD, Professor and Chair of the Department of Physiology at the University of Maryland School of Medicine, said:

“Our results open up a whole new class of potential antidepressant medications. 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.”

As things stand now, most people with depression are prescribed medications that raise levels of the neurochemical serotonin in the brain. These drugs, such as Prozac and Lexapro, are known as selective serotonin reuptake inhibitors, or SSRIs.

Regrettably, SSRIs are effective in less than half of patients with depression. Furthermore, even when these drugs work, they usually take between three and eight weeks to relieve symptoms.

This means that patients often suffer for months before they find a medicine that makes them feel better. In the case of patients who are suicidal, this can be deadly. Better treatments for depression are obviously needed.

GABA

Dr. Thompson and colleagues investigated another neurotransmitter besides serotonin, an inhibitory compound called GABA.

Brain activity is thought to be determined by a balance of opposing excitatory and inhibitory communication between brain cells. Dr. Thompson and his team hypothesize that in depression, excitatory messages in some brain regions are not powerful enough.

Since there is no safe way to directly strengthen excitatory communication, they focused on a class of compounds that reduce the inhibitory messages sent via GABA. They predicted that these compounds would restore excitatory strength.

The compounds, known as GABA-NAMs, minimize unwanted side effects because they are precise. In other words, they work only in the parts of the brain that are important for mood.

The compounds were tested in rats subjected to chronic mild stress that caused the animals to act in ways that mimic human depression.

Giving stressed rats GABA-NAMs successfully reversed experimental signs of a key symptom of depression, anhedonia, or the inability to feel pleasure. Amazingly, the therapeutic 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,” Dr. Thompson said. “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.”

Jonathan Fischell, Adam M Van Dyke, Mark D Kvarta, Tara A LeGates and Scott M Thompson
Rapid Antidepressant Action and Restoration of Excitatory Synaptic Strength After Chronic Stress by Negative Modulators of Alpha5-Containing GABAA Receptors
Neuropsychopharmacology (22 April 2015) | doi:10.1038/npp.2015.112

Photo:Fons Heijnsbroek/flickr