Fast-Acting Depression Drug Eases Symptoms in Hours

An experimental drug is able to rapidly improve the symptoms of depression in people who haven't responded to previous therapies, although the benefits are short-lived, a new study says.

People who took the experimental drug, known as AZD6765, showed improvements in their depression symptoms after just one hour and 20 minutes compared with those who took a placebo. This effect lasted for about 30 minutes, and some patients continued to see a benefit up to two days after treatment. 

On average, participants in the study had previously tried and failed seven rounds of treatment with various antidepressant therapies. Nearly half had failed to respond to electroconvulsive therapy (ECT), also known as "shock therapy."

Fast-acting drugs for major depression are urgently needed, said study researcher Dr. Carlos Zarate, of the National Institute of Mental Health. Current antidepressants typically take several weeks to start working, which can jeopardize a depressed person's health, particularly if he or she is at risk for suicide.

Another drug, calledketamine, has recently been shown to ease depression symptoms within hours, but its use has been limited because of serious side effects, including hallucinations. Ketaminehas also been used as a sedative and as a recreational drug.

The new findings suggest that researchers could potentially create a drug that works just as quickly as ketamine, but without the dangerous side effects, Zarate said.No harmful effects from AZD6765were seen during the study.

However, further research is needed to test whether different doses of the drug can produce more long-lasting effects, Zarate said.

Fast-acting therapies

Many antidepressants work by increasing levels of a brain chemical called serotonin, which is linked to mood. But ketamineand the experimental drug work a different way — they prevent the binding of a brain chemical called glutamate to nerve cells. Glutamate is also involved in mood regulation, Zarate said.

In the new study, half of the participants took AZD6765, which is given through an intravenous solution (IV), and half took a placebo. All participants filled out a survey assessing their level of depression immediately after taking the drug, and a few days after treatment. A week later, the groups switched the agent they took, so that everyone received the drug at some point during the study.

Overall, about one-third of the participants responded to the treatment — meaning they experienced at least a 50 percent reduction in their depressive symptoms during the study — compared with a 15 percent reduction in those who took the placebo.

The main side effects AZD6765 were headache, nausea and some problems concentrating, Zarate said. Patients did not have "out of body" experiences, which have been reported as a side effect of ketamine.

New treatments

"It's been well over two decades since we've had any major breakthroughs," in drug treatments for depression, said Steven Hollon, a  professor of psychiatry at Vanderbilt University in Nashville, who was not involved in the study. "Anything that can produce a rapid response in a refractory patient population has got real potential to help down the line."

The new drug may not produce serious side effects because it does not block glutamate binding as completely as ketamine does.

However, the new drug does not appear to work quite as well as ketamine. In a previous study, more than half of patients who took ketamine responded within an hour and 20 minutes (compared with 27 percent for AZD6765), and the antidepressant effects lasted for seven days.

Future studies may test higher or more frequent doses of the drug, or perhaps the drug can be developed as an oral form, Zarate said. Researchers may also test new drugs that target the glutamate system, he said.

The study was funded by the National Institutes of Health. The pharmaceutical company AstraZeneca owns a patent on AZD6765, and provided the study drug. One of the study authors works for AstraZeneca.

Pass it on: A new drug provides fast relief for depression symptoms, but so far, the effects are short-lived.

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