Semaglutide modulates explore/exploit decision-making in major depressive disorder: A randomized clinical trial.
Ziyuan Zhang, Ningyuan Chen, Darcy Wang et al.
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In 30 seconds
This secondary analysis of a randomized clinical trial examined whether semaglutide affected explore/exploit decision-making in 72 participants with major depressive disorder (MDD). Participants received oral semaglutide or placebo and completed a restless bandit task before and after 16 weeks of treatment; choices were assessed using computational modeling. Compared with placebo, semaglutide increased exploitation (ATE = 0.0242, p < 0.001), directed exploration (ATE = 0.0619, p = 0.013), and perseveration (ATE = 0.3017, p = 0.013). Effects were moderated by, but ultimately independent of, baseline characteristics and weight loss.
Key findings
- Semaglutide increased exploitation, or choosing the option with the highest expected reward (ATE = 0.0242, p < 0.001).
- Directed exploration, defined as choosing an option with greater uncertainty, increased with semaglutide (ATE = 0.0619, p = 0.013).
- Semaglutide also increased perseveration, the value-independent tendency to repeat the previous action (ATE = 0.3017, p = 0.013).
- Effects were moderated by, but ultimately independent of, baseline characteristics and weight loss during the trial.
Why it matters
The findings suggest that semaglutide may influence several components of decision-making in people with MDD, extending investigation of metabolic mechanisms in motivated behavior. Because the study assessed modeled task behavior rather than clinical outcomes, it does not establish whether these changes affect depressive symptoms or everyday functioning.
What to keep in mind
This was a secondary analysis with 72 participants and 16 weeks of follow-up; decision-making was assessed using a laboratory task and computational modeling.