Study shows ketamine can relieve depression within hours

The study found that people with treatment-resistant depression experienced symptom relief in as little as two hours with a single intravenous dose of ketamine, which is usually used in higher doses as an anesthetic in humans and animals. 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 US National Institutes of Health’s (NIH) National Institute of Mental Health (NIMH).

For this study, 18 treatment-resistant, depressed patients were randomly assigned to receive either a single intravenous dose of ketamine or a placebo. Depression improved within one day in 71% of all those who received ketamine, and 29% of these patients became nearly symptom-free within one day. In addition, 35% of patients who received ketamine still showed benefits seven days later. Participants receiving a placebo infusion showed no improvement.

This is among the first studies of humans to examine the effects of ketamine on depression. Used in very low doses, the medication is important for research, but it 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.

“The public health implications of being able to treat major depression this quickly would be enormous,” said NIH director Dr Elias Zerhouni. “These new findings demonstrate the importance of developing new classes of antidepressants that are not simply variations of existing medications.”

“To my knowledge, this is the first report of any medication or other treatment that results in such a pronounced, rapid, prolonged response with a single dose,” added NIMH director Dr Thomas Insel.

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.

The researchers who conducted the study now are zeroing in on other areas of the glutamate system. Specifying which components of the system are affected by compounds such as ketamine may help scientists understand how and why depression occurs, reveal biological markers that may one day aid in diagnosis, and point the way to more precise targets for new medications.