Neurology Central

Is rapid treatment of depression on the horizon with GABA-NAMs?

New preclinical findings have identified novel compounds that may hold the potential to treat depression in less than 24 hours. The study, published recently in Neuropsychopharmacology, presents a potential new avenue for faster treatment of depression with fewer side effects.

“Our results open up a whole new class of potential antidepressant medications,” commented lead researcher Scott Thompson from the University of Maryland School of Medicine (MD, USA). “We have evidence that these compounds can relieve the devastating symptoms of depression in less than 1 day, and can do so in a way that limits some of the key disadvantages of current approaches.”

Most of the current treatments for depression increase levels of serotonin in the brain, with the primary agents being selective serotonin reuptake inhibitors (SSRIs).The prevalent SSRIs demonstrate efficacy in only half of the depression patients who receive them – an effect that takes on average 3–8 weeks to manifest. This lag between receiving therapy and the resultant symptom relief can be detrimental to the patient, and thus the need for improved treatments for depression is clear.

Rather than serotonin, the team at Maryland investigated the inhibitory compound GABA. Working on the theory that excitatory messages in some brain regions are not strong enough in depression, they investigated compound that are able to reduce inhibitory messages in the brain that are sent via GABA. These compounds, termed GABA-NAMs, may both restore the strength of excitatory communication and minimize side effects due to their specificity.

The team administered GABA-NAMs to rats suffering from chronic mild stress with symptoms that resembled human depression. The GABA-NAMs successfully reversed experimental signs of a key symptom of depression – anhedonia – in the animals. Notably, the beneficial effects of the compounds became apparent within 24 hours – a rapidity that stands in stark contrast to the multiple weeks required for SSRIs to produce similar effects.

Further investigation revealed that GABA-NAMs effectively increased the strength of excitatory communication in regions of the brain that were weakened by stress. The compounds were also demonstrated to have no effect in unstressed animals, suggesting that they may not produce side effects in human patients.

“These compounds produced the most dramatic effects in animal studies that we could have hoped for,” concluded Thompson. “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.”

Source: University of Maryland School of Medicine press release