Semaglutide may improve motivation with major depressive disorder

Treatment with semaglutide significantly improves measures of motivation in patients with major depressive disorder (MDD), according to a study published April 29 in JAMA Psychiatry.

Hartej Gill, Ph.D., from University of Toronto, and colleagues assessed the effects of semaglutide, on reward-related dysfunction in a population with MDD. The analysis included 72 participants with a diagnosis of MDD and a body mass index ≥25 kg/m² who were randomly assigned to oral semaglutide (35 individuals) or placebo (37 individuals).

The researchers found that semaglutide-treated participants showed a pattern of increased willingness to exert physical efforts with higher expected values of reward (treatment × visit × expected value interaction: χ² = 12.024). Semaglutide’s effects on choice behavior were a result of reduced effort discounting, according to computational modeling. Semaglutide was associated with a significant reduction in sensitivity (β = −1.737), while there was no treatment effect on sensitivity to probability (β = −0.776).

“Semaglutide reduced the perceived cost of effort, relative to the monetary reward; the results of this trial have implications for the treatment of multiple neuropsychiatric disorders, which are characterized by varied reward dysfunctions,” the authors write.

Two authors disclosed ties to the pharmaceutical industry.

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