Semaglutide for the Treatment of Cognitive Dysfunction in Major Depressive Disorder

Prior treatment

• Current, or in the past 4 weeks, treatment with other oral hypoglycemic agents and/or insulin
• Substance use disorder within 3 months before screening or a positive baseline toxicology screen

Other illness

• Diagnosis of possible or probable Alzheimer's Disease, Mild Cognitive Impairment, or any other dementia
• History of neurological disorder, or evidence of neurologic or other physical illness that could produce cognitive deterioration
• DSM-5 diagnosis of obsessive compulsive disorder, posttraumatic stress disorder (current or within the last year), or borderline personality disorder as assessed by a study investigator
• Presence of absolute or relative contraindication to semaglutide (e.g. hypersensitivity to semaglutide, hepatic impairment, renal impairment with chronic kidney disease stage 3 and above, personal or familial history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2)
• History of diabetic retinopathy
• History of pancreatitis or pancreatic cancer
• Presence of clinically unstable general medical illness

Other

• Severe mood episode, defined as a Hamilton Depression Rating Scale (HAMD-17) score of \>23
• Actively suicidal or evaluated as being a suicide risk (operationalized as a score of ≥3 on HAMD-17 suicide item and/or by clinical assessment).
• Pregnancy or breastfeeding women

• Informed consent before study-related activity
• Individuals between the ages of 18 and 60 who meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for MDD
• Overweight (i.e. BMI ≥ 25 kg/m2)
• Below-average (i.e. \>1 SD below norm) performance in the Trail Making Test-B (TMTB)