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

1. Informed oral and written consent.
2. Diagnosed with unipolar disorder according to the criteria of ICD10 (International Classification of Diseases, World Health Organization (WHO)) or the DSM-V (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, the American Psychiatric Association
3. Hamilton Depression Rating Scale, 17-items (HDRS-17)47 score ≥14,
4. Age 18 years to 65 years (both included)
5. Body mass index (BMI) ≥27 kg/m2
6. Able to speak and understand Danish

Exclusion Criteria:

1. Any significant medical disorder or conditions that contraindicate the investigational drug, e.g., pregnancy, presence of known allergy GLP-1 receptor agonists, severe neurological disorder, on-going drug, or alcohol abuse
2. Coercive measures
3. Females of childbearing potential who are pregnant, breast-feeding or have the intention of becoming pregnant within the next 9 months (26 weeks plus two months after discontinuation of semaglutide), or are not using contraceptives (during the whole study period) considered as highly effective (combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) intrauterine device - IUD, IUS, bilateral tubal occlusion, vasectomised partner, sexual abstinence)
4. Patients treated with corticosteroids or other hormone therapy (except oestrogens).
5. Any active substance abuse or dependence (except for nicotine)
6. Impaired hepatic function (plasma liver transaminases >2 times upper normal limit).
7. Impaired renal function (serum creatinine >150 μmol/l)
8. Cardiac problems defined as decompensated heart failure (NYHA class III/IV), unstable angina pectoris, and/or myocardial infarction within the last 12 months
9. Hypertension with systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg
10. Impaired pancreatic function (acute or chronic pancreatitis and/or plasma amylase >2 times upper normal limit). Receiving any experimental or pre-marketing drug within the last 3 months
11. Use of diabetes medication or weight-lowering pharmacotherapy e.g. semagultid within the preceding 3 months
12. Known type 1 and 2 diabetes or HbA1c>48mmol/l
13. Suicidal behaviour as judged by the investigator and based on clinical evaluation. At all contact with patient attendance (please see Table 1) possible suicidality will be evaluatedaccording to the guidelines. If the patient is evaluated as suicidal, the person will be excluded from the study and evaluated by a senior consultant in psychiatry, who will take further action.
14. Any condition that the investigator feels would interfere with trial participation.