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Automated positive feedback could prolong ketamine’s antidepressant effects: study

“​​This automated intervention is so simple that it could be repurposed to address a variety of mental health conditions.”

Story at a glance


  • Traditional medications are ineffective for many patients with depression, creating an opportunity for alternatives. 

  • In a new study, researchers found positive feedback delivered via computer helped prolong the antidepressant effects of ketamine.

  • Ketamine is the only psychedelic approved by the Food and Drug Administration to treat treatment-resistant depression.

Seeing smiling faces or receiving encouraging words may help prolong the amount of time a dose of ketamine treats depression, according to results of a new study. 

Patients who received ketamine and completed self-esteem boosting trainings within one to four days of the infusion remained depression-free for up to 30 days, while those who received just ketamine often tended to relapse within two weeks. 

Writing in the American Journal of Psychiatry, researchers explained ketamine is thought to reverse depression by rapidly enhancing neuroplasticity, or the brain’s ability to change. 

Ketamine is the only psychedelic medicine approved by the Food and Drug Administration for treatment-resistant depression. The substance also has a rapid onset of antidepressant properties, setting it apart from traditional treatments that can take weeks to become effective. 

However, the effects of a ketamine infusion quickly dissipate, limiting the substance’s clinical use. 


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To determine whether an automated, computer-based approach designed to boost patients’ self-esteem could leverage the enhanced neuroplasticity of a ketamine infusion, researchers randomized 154 adults to receive ketamine treatment alone or in combination with positive feedback training. Each patient underwent a total of eight training sessions that lasted under 20 minutes each.

Some patients received a saline solution instead of ketamine as a placebo, and others completed a sham version of the behavioral intervention after taking ketamine. All participants had major depressive disorder and had been unsuccessfully treated at least once for the condition. Individuals were between the ages 18 and 60.

“After priming the brain with ketamine, training positive self-associations could provide an efficient, low-cost, portable, noninvasive, and highly dissemination-ready strategy for leveraging and extending ketamine’s rapid antidepressant effects,” authors wrote. 

They caution the results need to be replicated in other studies but could spell hope for patients with treatment-resistant depression who’ve exhausted other options. 

In 2020, around 21 million Americans experienced at least one major depressive episode, while around 9 million are diagnosed with depression each year. 

“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,” said study author Rebecca Price of the University of Pittsburgh School of Medicine in a release.

“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 and her team hope to make the computer intervention as accessible as possible to extend time between ketamine infusion appointments and save patients money. 

A provisional patent has been filed for the novel treatment approach, while researchers are testing whether competing the treatment on a smartphone or iPad yields similar results.

“​​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,” Price said.

“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.”

Published on Nov 01,2022