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Smiling Faces Appear To Prolong Antidepressant Effects Of Ketamine

Recent studies have consistently demonstrated the strong efficacy of ketamine-assisted therapy (KAT) as a highly effective treatment for depression. Scientists attribute the antidepressant qualities of ketamine to the rapid enhancement of neuroplasticity immediately following treatment.

Although the antidepressant effects of ketamine are experienced within a short period, often a couple of hours, after an infusion, the effects tend to wear off over the course of the following weeks.

A group of researchers recently conducted a double-blind, randomized clinical trial to see if an automated, computer-based approach that reinforces positive self-image in patients can be helpful in extending the anti-depressant effects of ketamine by leveraging the enhanced neuroplasticity immediately following a ketamine infusion.

The results published in The American Journal Of Psychiatry suggest that digital neurocognitive training during the heightened brain elasticity period can indeed prolong the antidepressant effects of ketamine for at least one month.

To conduct this study, researchers enrolled 154 adults with treatment-resistant depression were enrolled and randomly assigned to one of three groups. The active therapeutic group received ketamine infusion along with active “automated self-association training” [ASAT]. The control groups were either assigned ASAT with a placebo infusion (saline) or a ketamine infusion with a sham ASAT.

The ASAT was designed to leverage Pavlovian conditioning to promote positive implicit self-associations and self-worth. The intervention was delivered over eight 20-minute sessions twice daily over 4 days starting 24 hours after the infusion. The sessions included both verbal and pictorial stimulus pairings to practice and reinforce implicit associations between positive traits like the words “sweet,” and “attractive,” and photos of smiling actors, with self-referential stimuli like “I,” and the participant headshots.

Follow-up assessments showed that people in the ketamine + ASAT group reported fewer depression symptoms for a longer period than those in the control groups who did not receive ketamine or ASAT. These findings suggest that the neurocognitive training extended the antidepressant effects of ketamine.

Rebecca Price, Ph.D., associate professor of psychiatry at Pitt’s School of Medicine who led the research efforts, 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.”

Dr. Price sees her and her team's findings as a promising solution toward supporting expanded access and affordability of ketamine therapy to more populations. Extended time in between ketamine treatments effectively reduces costs for patients and allows providers to serve a larger group of patients.

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."


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