Results from a new study suggest that the antidepressant effects of ketamine can be prolonged in people with treatment-resistant depression through computer-based neurocognitive training.
Results from a clinical trial conducted suggest that low-cost, automated behavioural interventions during the window of heightened brain plasticity, after a single ketamine treatment, might help to keep depression in check for at least one month.
The researchers suggest that using positive words and pictures designed to boost self-worth prolongs the antidepressant effects.
Results from the double-blind, randomised clinical trial, conducted at the University of Pittsburgh, have been published in the American Journal of Psychiatry.
Long-lasting depression treatments
The researchers emphasis that the findings are an important step towards long-lasting depression treatments for patients who have exhausted other options.
An analysis by the National Institute of Mental Health shows that nearly 21 million American adults experienced at least one major depressive episode in 2020, and about 9 million adults are diagnosed with depression annually, with nearly 3 million not responding to traditional antidepressant medication.
Research suggests that ketamine could offer an alternative chance at long-term remission, however, the treatment has its limitations.
Ketamine is a fast-acting antidepressant, meaning symptom relief from depression can be felt as early as two hours after an infusion, but these effects tend to wear off in the following weeks.
This drives patients to go back for another infusion, which are associated with high out-of-pocket costs and often have long wait lists, meaning not all patients who might benefit from the treatment can get it.
Rebecca Price, Ph.D., associate professor of psychiatry in Pitt’s School of Medicine, commented: “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.
“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.”
Price, whose research focuses on identifying neurocognitive mechanisms of mood and anxiety disorders, was among the first to show that intravenous ketamine can reduce suicidal thoughts.
Now, Price and her team are focused on improving the accessibility of ketamine therapy and broadening its clinical potential by pairing the drug with computer-based digital therapies.
Price continued: “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 strategy pairs a single ketamine injection with automated computer-based training that uses positive words and imagery to influence how a person sees themselves. Words like “sweet,” “loveable” and “worthy” appear on the screen along with the patient’s photo and images of people smiling.
Improving patient outcomes
More than 150 adults with treatment-resistant depression were enrolled in the trial.
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. These findings suggest that the neurocognitive training extended ketamine’s antidepressant effects.
Based on these initial findings, Pitt’s Innovation Institute has filed a provisional patent for this novel treatment approach.
Researchers are now testing whether doing the training on an iPad or smartphone offers the same benefit as completing it on a computer in the clinic, and ongoing research is also exploring how similar techniques could help ease suicidality. The researchers suggest that future research may expand to anxiety, disordered eating and more.
Price added: “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,.
“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.
