Millions of Americans with depression function perfectly well using common treatments, but there are those whose disease shows resistance to most drugs. Researchers this week announced some hope for those people in new research that could eventually lead to a treatment for treatment-resistant depression – and that hope is coming from an unlikely place.

Researchers at the University of Texas Southwestern Medical Center this week announced new research into a drug that could form the basis of a new rapid-acting antidepressant. The drug, memantine, acts on the brain’s NMDA receptors – those known to play a role in treating depression. The researchers believe that their findings could eventually lead to a treatment that blocks NMDA receptors and better controls depression with fewer side effects. Memantine is currently approved by the FDA for use in treating Alzheimer’s disease.

Memantine is chemically similar to ketamine, a drug best known for its recreational uses. Ketamine is known to produce a fast-acting antidepressant effect in patients. However, ketamine’s other effects and recreational use make it unsuitable for the treatment of depression. Memantine reacts with the same brain receptors as ketamine, though researchers have found that it doesn’t produce the same antidepressant effect. The UT researchers are hoping that their studies will lead to a fast-acting antidepressant that doesn’t have the side effects of ketamine.

“Although, both ketamine and memantine have similar actions when nerve cells are active, under resting conditions, memantine is less effective in blocking nerve cell communication compared to ketamine,” said Lisa Monteggia, one of the researchers and a professor of Neuroscience at UT. “This fundamental difference in their action could explain why memantine has not been effective as a rapid antidepressant.”

Monteggia and her colleagues are currently examining the molecular basis of how nerve cells communicate, to determine why ketamine and memantine produce different effects. The team is also researching antidepressant efficacy, and what bodily systems contribute to different drugs’ effects.

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