People with treatment-resistant depression experienced symptom relief in as little as two hours with a single intravenous dose of ketamine, a medication usually used in higher doses as an anesthetic in humans and animals, in a preliminary study. Current antidepressants routinely take eight weeks or more to exert their effect in treatment-resistant patients and four to six weeks in more responsive patients — a major drawback of these medications. Some participants in this study, who previously had tried an average of six medications without relief, continued to show benefits over the next seven days after just a single dose of the experimental treatment, according to researchers conducting the study at the National Institutes of Health's National Institute of Mental Health.
This is among the first studies of humans to examine the effects of ketamine on depression, a debilitating illness that affects 14.8 million people in any given year. Used in very low doses, the medication is important for research, but is unlikely to become a widely used clinical treatment for depression because of potential side effects, including hallucinations and euphoria, at higher doses. However, scientists say this research could point the way toward development of a new class of faster- and -longer-acting medications. None of the patients in this study, all of whom received a low dose, had serious side effects. Study results were published in the August issue of the Archives of General Psychiatry.
Ketamine blocks a brain protein called the N-methyl-D-aspartic acid (NMDA) receptor. Previous studies have shown that agents that block the NMDA receptor reduce depression-like behaviors in animals.
NMDA receptors are critical for receiving the signals of glutamate, a brain chemical that enhances the electrical flow among brain cells that is required for normal function. Studies indicate that dysregulation in glutamate could be among the culprits in depression. Using ketamine to block glutamate�s actions on the NMDA receptor appears to improve function of another brain receptor — the AMPA receptor — that also helps regulate brain cells' electrical flow.
Scientists think the reason current antidepressant medications take weeks to work is that they act on targets close to the beginning of a series of biochemical reactions that regulate mood. The medications� effects then have to trickle down through the rest of the reactions, which takes time. Scientists theorize that ketamine skips much of this route because its target, the NMDA receptor, is closer to the end of the series of reactions in question.
NIMH Press Office
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