The new power of positive thinking

Cognitive training enhances ketamine therapy for people with severe depression.
Illustrated by
Getty Images/Tasha Art

Imagine if your brain could reroute itself away from depressive thoughts just as easily as your car’s GPS reroutes itself when you make a wrong turn.

Rebecca Price, a PhD associate professor of psychiatry in Pitt’s School of Medicine, thinks a similar concept could help the roughly 30% of depression patients whose illness doesn’t respond to traditional treatments. Using an approach that incorporates computer-based neurocognitive training, Price is prolonging the antidepressant effects of ketamine therapy. 

In a study published in The American Journal of Psychiatry, Price found that showing positive words and images to people with treatment-resistant depression after a single ketamine infusion can help them quickly learn new ways of processing information that lead to happier thoughts.

Ketamine has been used worldwide as an anesthetic in medical settings for more than half a century. Around 2000, researchers began noticing and testing its quick-acting efficacy against depression. Soon, there was enough evidence to prompt clinicians to start prescribing it off-label for treatment-resistant depression, and clinics began opening across the country to administer intravenous ketamine therapy.  

Price became interested in ketamine’s potential while a graduate student in clinical psychology at Rutgers University. Her mentor connected her with investigators at the Icahn School of Medicine at Mount Sinai who were conducting some of the earliest studies on ketamine use for depression treatment. As a clinician interviewer for those studies, Price was floored by the nearly immediate ability of ketamine to transform a patient’s thinking.  

“I would speak to a patient one day and they would be describing decades of chronic depression that had not ever really remitted to any approach they tried,” says Price, who is also an associate professor of psychology at Pitt. “Then I would come back the following day and it was like speaking to almost a totally different person.”

However, the benefits tend to be short-lived, with symptoms of depression returning in a matter of a weeks after an infusion. Price is working to change that.

A “psychoplastogenic” drug, ketamine quickly increases the brain’s plasticity, or ability to adapt in response to stimuli. In a study involving 154 adults, Price was able to capitalize on the brain’s malleable period following a single dose of ketamine by adding an automated self-association training twice daily over four consecutive days.

In the training, a patient might be shown words like “sweet” or “attractive” or a photo of a smiling actor. The platform would pair that positive image with an image of the patient or the word “I.” In the group of 53 participants who received both the single dose of ketamine and the self-association training, the “package deal” was shown to prolong depression relief for three months.

Extending the effects of a single ketamine dose could dramatically increase the ability of patients to access the treatment. Patients get started with anywhere from four to eight infusions administered in the first few weeks and return for booster doses as necessary, often creating long waiting lists at clinics. (Although most health insurance plans don’t cover ketamine treatments.)

“I’ve been flooded with requests from ketamine providers, patients and their families,” Price says. Some of her colleagues wonder if the same type of therapy could be adapted to treat phobias, eating disorders or similar conditions. Pitt has filed a provisional patent for the combined treatment protocol.

Price is now testing her protocol in hospitalized patients who have just attempted suicide. She is also seeking next-step funding to study either making the combination treatment powerful enough so that it lasts longer than three months or determining what form of intervention at that juncture could help boost its effects. Although there is more to do, Price’s work already offers a great deal of practical hope for what’s often a devastating condition.