Moving Beyond SSRIs: Fast-Acting Experimental Depression Drugs Show Strong Results In Animals

depression
Researchers say they have identified promising new drug candidates that could treat depression in less than 24 hours while minimizing side effects. Eddi van W, CC by 2.0

Selective serotonin reuptake inhibitors (SSRIs), the well-advertised depression drugs, typically take several weeks to relieve symptoms. A new University of Maryland School of Medicine study has identified promising new drug candidates that researchers say could treat depression in less than a day while minimizing side effects.

“These compounds produced the most dramatic effects in animal studies that we could have hoped for,” Dr. Scott Thompson, professor and chair of the department of physiology, stated in a press release. “It will now be tremendously exciting to find out whether they produce similar effects in depressed patients.”

SSRIs, such as Prozac and Lexapro, increase levels of the neurochemical serotonin in the brain. Unfortunately, SSRIs are effective in only about one third of all patients with depression, Thompson and his colleagues say, and, when they do work, they typically take between three and eight weeks to kick in and begin relieving symptoms. Depressed people, then, may suffer for months before finding the right drug and in the case of suicidal patients, this lag time can be deadly. Surprisingly, there are other good reasons to search for SSRI alternatives when treating depression.

Addiction By Another Name?

An alarming effect linked to SSRIs is so-called “discontinuation syndrome.” A recent article appearing in Psychotherapy and Psychosomatics reviewed past studies all of which focused on what happens when patients stop taking their depression medicines. The authors of that study say "withdrawal-like symptoms," including nausea, fatigue, agitation, loss of concentration, and in some cases a flu-like illness, typically occur within a few days and last a few weeks following drug discontinuation.

“Clinicians need to add SSRIs to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with benzodiazepines, barbiturates, and other psychotropic drugs,” the authors wrote. Meanwhile, Scientific American reports about eight to 10 percent of Americans take an antidepressant, with SSRIs being the "dominant class of depression drug."

For the current study, Thompson and his colleagues examined drugs that work on another neurotransmitter besides serotonin: GABA. In practice, brain activity is a balance of opposing signals between brain cells, those that excite communication and those that inhibit it. GABA falls into the inhibition camp. A quick search of the Internet reveals many people refer to this neurotransmitter as “natural valium.”

Too much valium, natural or not, might be depressing, so Thompson and his colleagues examined a class of compounds that reduce the messages sent via GABA. Called GABA-NAMs, these compounds work only in the parts of the brain essential to mood.

The experiments began with rats subjected to chronic mild stress. This caused the animals to act in ways that resemble human depression. Giving the stressed rats GABA-NAMs, the researchers reversed signs of one key symptom of depression — anhedonia, or the inability to feel pleasure. Beneficial effects appeared within 24 hours — much faster than the multiple weeks needed for SSRIs to produce the same effects.

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

Source: Fischell J, Van Dyke AM, Kvarta MD, LeGates TA, Thompson SM. Rapid Antidepressant Action and Restoration of Excitatory Synaptic Strength After Chronic Stress by Negative Modulators of Alpha5-Containing GABAA Receptors. Neuropsychopharmacology. 2015.

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