Taking Ketamine and Looking at Smiling Faces is a Therapy That Could Help End Depression, Shows Clinical Trial

Being given an illicit drug called ketamine and then looking at smiling faces could help end depression, according to a new study.

Researchers found that reading happy words and looking at happy faces, including one’s own, can prolong ketamine’s antidepressant effects for months.

Besides its use as an illicit party drug, ketamine was approved by the US FDA in 1970 for use as an anesthetic to kill pain, and was used in treating injured soldiers on the battlefields in the Vietnam War.

Doctors began to realize that the drug had powerful effects against depression and suicidal thoughts: Called ‘the speedster of antidepressants’ because it works within hours, emergency responders sometimes give it to agitated people rescued from suicide attempts.

In a new therapy developed at the University of Pittsburgh for those suffering with treatment-resistant depression, just one ketamine injection was followed by automated computer-based training that used positive words and imagery to improve how a person sees themselves.

Words such as “sweet”, “lovable” and “worthy” will flash on a screen alongside the patient’s photo and pictures of smiling people.

The scientists behind the plan have found depression can be kept at bay for at least a month if the digital techniques are used when ketamine has prepared the brain’s plasticity.

“Using simple conditioning during the period after ketamine treatment, when the brain is receptive to soaking in new information, allows us to go after key features of depression,” reports Dr. Rebecca Price, an Associate Professor of Psychiatry at the school.

“Training the brain to link perceptions of yourself with positive ideas during this ketamine-primed plasticity window exceeded my expectations.

“I was surprised and amazed to get such clear findings from an intervention that was so minimal.”

The results of the double-blind, randomized clinical trial conducted locally in Pennsylvania were published last month in the American Journal of Psychiatry.

According to a National Institute of Mental Health analysis, nearly 21 million American adults experienced at least one major depressive episode in 2020–and nearly 3 million of those diagnosed do not respond to traditional antidepressant medication. For people with such treatment-resistant depression, psychoactive drugs, such as ketamine, offer an alternative chance at long-term remission.

Though symptom relief can be felt just two hours after a ketamine infusion, the drug’s effects often wear off after a couple of weeks meaning patients go back for more. It’s not an easily accessible treatment either: In the US, ketamine infusions often come with high out-of-pocket costs and long waiting lists.

As a result, Dr Price and her team are reorienting their goals to improve access to intravenous ketamine treatment and boost its effect by pairing the drug with digital therapies.

“We are interested in creating an automated intervention that any computer or device can run, making it as accessible as possible.

“Our goal is to leverage digital technologies and develop a strategy that will efficiently extend time between appointments, save patients money and get more patients effective depression care.”

The clinical trial enrolled more than 150 adults with treatment-resistant depression. Following a ketamine infusion, one group of patients completed eight 20-minute trainings over four days, and another group received a non-therapeutic version of the computer tasks. A third group received a saline infusion followed by the active training. In the following month, people in the ketamine-plus-training group reported feeling fewer depression symptoms for longer than those who did not receive training or who did not receive ketamine, suggesting that the neuro-cognitive training extended ketamine’s antidepressant effects.

Based on the findings, Pittsburgh’s Innovation Institute filed a provisional patent for the treatment method, to benefit those who have exhausted all other options.

Currently the team are figuring out how they could get the content on an iPad or smartphone and bring patients the same benefits that they receive on a computer in a clinic.

Ongoing research is also exploring how similar techniques could help ease suicidality, and future research may expand to anxiety, disordered eating, and more.

“This automated intervention is so simple that it could be repurposed to address a variety of mental health conditions and easily tweaked to match the needs of an individual patient,” said Price, who was among the first to show that intravenous ketamine can reduce suicidal thoughts

“If playing little digital games is what it takes to maintain a response and reliably get one month of depression relief, that’s already an improvement over the status quo.”