Smiling faces can help the drug ketamine keep depression at bay

Computer games designed to boost confidence appear to prolong the antidepressant effects of the mind-bending anesthetic ketamine.

A recent study of 154 people found that those who played games with smiley faces and positive messages remained depression-free for up to three months after an infusion of ketamine. American Journal of Psychiatry.

People given ketamine alone tended to relapse after a week or two.

The results are important because “we need new approaches to help people feel better faster and help them stay better,” says Rebecca Price, study author and associate professor of psychiatry and psychology at the University of Pittsburgh.

Established medications like Prozac and Zoloft can take weeks to relieve depression and don’t work for every patient. Ketamine can offer immediate relief, but the effects often wear off after a few days or weeks.

“And then going back for infusions over and over again to keep that relief going can be really burdensome and expensive,” Price says, “and it’s just not accessible to all patients.”

How to prolong the antidepressant effect of ketamine

So Price and a team of scientists wanted to find a way to prolong the antidepressant effects of ketamine. They decided to focus on a common symptom of depression: low self-esteem and self-loathing.

The team drew on research that suggested that ketamine temporarily causes certain areas of the brain to enter a state in which they make lots of new connections. During this period, the brain appears to be more receptive to learning and change.

“So we tried to use this window of opportunity right after ketamine to strengthen associations specifically between the thought of me, me, and positive information and traits,” says Price.

The team had some participants play special computer games for 30 to 40 minutes a day for four days after receiving an infusion of ketamine.

Finding ways to reinforce positive connotations in the brain

In games that included words, every time a player saw the letter “I,” positive expressions like “good, nice, sweet, kind, etc.,” Price says, followed.

In other games, participants were asked to click on a photo—their own or someone else’s—once it flashed on one area of ​​the screen.

“Every time they click their own photo, a smiley face will appear right after in the same spot,” says Price.

The games had a surprisingly powerful effect.

“By doing these really simple computer exercises, we could extend the antidepressant effect of a single infusion of ketamine for at least a month,” says Price, adding that the effect could last up to three months.

If these results hold up in larger studies and over a longer period of time, this approach could make ketamine treatment much more affordable, says Dr. Sanjay Mathew, professor of psychiatry at Baylor College of Medicine and co-author of the study.

Right now, insurance rarely covers treatment, and a single ketamine infusion can cost anywhere from $300 to more than $800. “This is obviously a huge challenge for many patients and the biggest reason we can’t send more patients to ketamine,” says Matthew.

Costs are even higher for patients receiving a nasal version of ketamine called Spravato, which has received approval from the Food and Drug Administrationl to treat suicidal depression and depression that has not responded to other treatments.

An automated, computerized adjunct to ketamine treatment would be welcome right now because mental health professionals are in short supply, Mathew says.

“It could be widely disseminated in clinics that don’t have the resources to engage in any number of psychotherapies that work on self-esteem and self-belief,” he says.

It’s also possible that a combination approach could work for other conditions treated with ketamine, including addiction and alcohol use disorder, Mathew says.

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