AZD6765 - a novel experimental drug could ease out depression without any adverse side effects, say researchers.
Prescription anti-depressants, working through the brain's serotonin system, take weeks to work, which might prompt severely depressed to commit suicide.
Ketamine also works in hours, but its usefulness is limited by its potential for side-effects, including hallucinations. It is being studied mostly for clues to how it works.
"Our findings serve as a proof of concept that we can tap into an important component of the glutamate pathway to develop a new generation of safe, rapid-acting practical treatments for depression," said Carlos Zarate, of the NIH's National Institute of Mental Health, which conducted the research, the journal Biological Psychiatry reported.
AZD6765, like ketamine, works by blocking glutamate binding to a protein on the surface of neurons, called the NMDA receptor. It is a less powerful blocker of the NMDA receptor, which may be a reason why it is better tolerated than ketamine, according to an NIH statement.
About 32 percent of treatment-resistant depressed patients infused with ASD6765 showed a clinically meaningful response at 80 minutes after infusion that lasted for about half an hour - with residual effects lasting two days for some.
Conversely, 52 percent of patients receiving ketamine show a comparable response, with effects still detectable at seven days. So a single infusion of ketamine produces more robust and sustained improvement, but most patients continue to experience some symptoms with both drugs.
However, depression rating scores were significantly better among patients who received AZD6765 than in those who received placebos.
The researchers deemed this noteworthy, since, on average, these patients had failed to improve in seven past antidepressant trials, and nearly half failed to respond to electroconvulsive therapy (ECT).
Zarate and colleagues say their results warrant further trials with AZD6765, testing whether repeated infusions a few times per week or higher doses might produce longer-lasting results.