Does Semaglutide Improve Depressive Symptoms in Patients With Major Depressive Disorder and Overweight or Obesity

This 26 week, randomized, double-blinded, placebo-controlled clinical trial investigate effects of semaglutide once-weekly vs. placebo on depressive symptoms in patients with unipolar disorder and comorbid obesity or overweight aged 18 years to 65 years. The primary endpoint is the change in depressive symptoms measured as difference in the 12-item self-report mood questionnaire Major Depression Inventory (MDI) from week 0 to week 26. Participants will be randomized to receive once-weekly injection of either semaglutide or placebo. Patients will be treated for 26 weeks with an initial dose of semaglutide of 0.25 mg once weekly for four weeks, 0.50 mg once weekly for four weeks 1.0 mg for four weeks, 1.7 mg for four weeks and finally 2.4 mg for the remaining treatment period. Assessments will be conducted at weeks 0, 4, 8, 12, 16, 20, 24, and 26. Adherence and adverse events will be assessed during the entire treatment period. In addition, heart rate, blood pressure, height, body weight, waist and hip circumference will be recorded. The diagnosis of depression will be confirmed at baseline and depressive symptoms will be assessed with Hamilton Depression Rating Scale (HAM-D17) at baseline week 0, 12 and 26. MDI will be completed monthly. Participants will also complete questionnaires on physical activity, cognitive complaints, perceived stress, the reward system, Quality of life, alcohol use, and sleep quality at baseline and week 26.