Semaglutide in Comorbid Schizophrenia Spectrum Disorder and Obesity

Inclusion Criteria:

• Stable outpatients or inpatients aged 18-70 years, diagnosed with schizophreniaspectrum disorder, or major depressive disorder with psychotic features, or bipolardisorder (does not need to have psychotic features)
• On maintenance treatment with an AP (stable dose for ≥3 months)
• BMI must be ≥30 kg/m2, OR ≥27 kg/m2 with the presence of at least one weight-relatedcomorbidity (treated or untreated): hypertension, dyslipidaemia, obstructive sleepapnea, or impaired fasting glucose, OR BMI ≥25 with individual having gained >5%bodyweight in association with AP treatment
• History of either failure to tolerate metformin or failure to lose ≥5% body weightover at least 16 weeks on the highest tolerated trial of metformin, and who are notcurrently being treated with metformin (minimum of 1 week metformin-free prior tostudy entry)

Exclusion Criteria:

• Patients with severe substance disorder other than tobacco or caffeine use disorder;only severe substance use disorder is exclusionary for cannabis use
• Liver, or renal dysfunction
• A positive drug urine screen other than cannabis as per PI discretion
• Sexually active females of child-bearing age not on a regular contraceptive, ornursing or with a positive pregnancy test
• Clinical or laboratory evidence of uncompensated cardiovascular, endocrine,haematological, or pulmonary disease
• History of reactive hypoglycaemia
• Treatment within 3 months, or failure to tolerate GLP-1RA
• Type 1 Diabetes (T1D) or current diagnosis of Type 2 Diabetes (T2D), diagnosis of T2Don OGTT screen, or HbA1c > 6.5%
• Use of Health Canada approved weight-lowering agents, warfarin, coumarin derivatives,or medication with significant renal impact
• Major medical or surgical event within the preceding 3 months
• Personal or family history of medullary thyroid carcinoma or multiple endocrineneoplasia syndrome
• History of pancreatitis or elevated amylase on screen
• History of severe gastrointestinal disease, (i.e. gastroparesis)
• Acute suicidal risk
• Uncompensated thyroid disorder
• History of heart rhythm disturbances, conduction system abnormalities, or evidence ofclinically relevant abnormalities on screening ECG.
• Any condition that interferes with the safe acquisition of MRI data such as metalimplants, pacemakers, aneurysm clips, cochlear implants (only for the MRI component;can participate in the remainder of the trial)
• History of gallstones with intact gallbladder or those at increased risk ofgallbladder complications (with intact gallbladder)