Smiling pictures increase the effects of ketamine’s antidepressant

Simple computer-based neurocognitive training – using positive words and images designed to boost self-esteem – prolongs the antidepressant effects of ketamine in people with treatment-resistant depression, researchers report.

Results of a randomized, double-blind clinical trial conducted in Pittsburgh suggest that low-cost automated behavioral interventions during the window of intense brain plasticity after a single ketamine treatment may help keep depression under control for at least one month.

The findings are an important step toward long-term depression treatments for patients who have exhausted other options.

“Using simple conditioning during the period after ketamine treatment, when the brain is receptive to immersion in new information, allows us to follow key features of depression,” says Rebecca Price, MD, assistant professor of psychiatry at the University of Pittsburgh School of Medicine.

“Training the brain to associate your perceptions of yourself with positive thoughts during the ketamine-filled plasticity window exceeded my expectations. I was surprised and amazed to get such clear results from an intervention that was so little.”

According to a National Institute of Mental Health analysis, approximately 21 million Americans experienced at least one major depressive episode in 2020. About 9 million adults are diagnosed with depression annually, and about 3 million do not respond to conventional antidepressant medications.

For people with treatment-resistant depression, psychoactive drugs, such as ketamine, provide an alternative chance for long-term recovery.

Since antidepressants Effects Ketamine was first reported in the medical literature nearly two decades ago, and clinics providing intravenous ketamine have expanded from academic medical centers to specialist practices across the country. When administered in and appropriately monitored medical settings, the injections are safe and do not lead to drug dependence, while providing therapeutic benefits for people with treatment-resistant depression.

But treatment has its limits. While symptom relief can be felt as early as two hours after the infusion, the effects of ketamine tend to wear off in the following weeks, prompting patients to come back for another injection. Ketamine injections are associated with high out-of-pocket costs and often have long waiting lists, so not all patients who might benefit from treatment can get them.

Price, whose research focuses on identifying the neurocognitive mechanisms of mood and anxiety disorders, was among the first to show that intravenous ketamine can reduce suicidal thoughts. Now, she and her team are focused on improving the accessibility of ketamine therapy and expanding its clinical potential by pairing the drug with computer-based digital therapies.

“We’re interested in creating an automated intervention that any computer or device can run, making it as accessible as possible,” Price says. “Our goal is to take advantage of digital technologies and develop a strategy that will efficiently extend the time between appointments, save patients money and get more effective depression care.”

The strategy developed by Price combines a single injection of ketamine with automated computer-based training that uses positive words and images to influence how a person sees themselves. Words such as ‘sweet’, ‘lovable’ and ‘worthy’ appear on the screen along with the patient’s picture and pictures of smiling people.

The clinical trial included more than 150 adults with treatment-resistant depression. After the ketamine injection, one group of patients completed eight 20-minute training sessions over four days, and another group received a non-treatment version of the computer tasks. A third group received a saline infusion followed by active training.

In the following month, people in the ketamine plus training group reported feeling fewer depressive symptoms for a longer time than those who neither trained nor received ketamine, suggesting that neurocognitive training increased the effects of ketamine’s antidepressant.

Now, researchers are testing whether training on an iPad or a smartphone offers the same benefit as completing it on a computer in the clinic. Ongoing research is also exploring how similar techniques can help alleviate suicide, and future research may expand to include anxiety, disordered eating, and more.

“This robotic intervention is so simple that it can be redirected to treat a variety of mental health conditions and can be easily modified to suit the needs of the individual patient,” Price says. “If playing a few digital games is what it takes to keep responsive and get a month of depression reliably on it satisfactionThis is really an improvement from the status quo.”

The search appears in American Journal of Psychiatry. Additional authors for this study are from the University of Pittsburgh and Baylor College of Medicine, Texas.

Based on these initial findings, the Pete Institute of Innovation has filed a provisional patent for the new treatment approach.

source: University of Pittsburgh