Effect of Tirzepatide on Alcohol Intake and Reward Processing in Patients Diagnosed With Schizophrenia and Alcohol Use Disorder

Exclusion criteria

• Intellectual Disability: individuals with a diagnosis of intellectual disability.
• Acute Psychosis: Acute exacerbation of psychosis, as indicated by a score of 6 or 7 on the Clinical Global Impression-Severity (CGI-S) scale.
• Coercive Measures: Current use of coercive measures, which includes individuals sentenced to treatment ('dom til behandling').
• Suicidal Behaviour: Evidence of current severe suicidal behaviour, as assessed by the investigator during clinical evaluation.
• History of Severe Alcohol Withdrawal: History of delirium tremens or alcohol withdrawal seizures.
• Severe Withdrawal Symptoms: Clinical Institute Withdrawal Assessment of Alcohol Scale, revised (CIWA-Ar) score greater than 9 at baseline examination.
• Severe Neurological Conditions: Presence of severe neurological diseases, including severe traumatic brain injury.
• Diabetes: Type 1 or 2 diabetes
• Pregnant or Potentially Pregnant Women: WOCBP who are pregnant, breastfeeding, intend to become pregnant within the next 6 months (including 16 weeks of treatment plus two months after discontinuation of semaglutide), or are not using a highly effective contraceptive method throughout the study period. Highly effective methods include combined hormonal contraception (oral, intravaginal, transdermal), progestogen-only hormonal contraception (oral, injectable, implantable), intrauterine device (IUD), intrauterine system (IUS), bilateral tubal occlusion, vasectomised partner, or sexual abstinence. WOCBP with a measured serum human chorionic gonadotropin (hCG) level greater than 3 U/L at inclusion will also be excluded.
• Liver Function: Impaired hepatic function, defined as liver transaminases greater than three times the upper limit of normal.
• Renal Function: Impaired renal function, indicated by an estimated glomerular filtration rate (eGFR) below 50 mL/min and/or plasma creatinine above 150 μmol/L.
• Pancreatic Function: History of acute or chronic pancreatitis or amylase levels more than twice the upper limit of normal.
• Thyroid Conditions: Previous medullary thyroid carcinoma (MTC) or a family history of MTC and/or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• Cardiac Issues: Decompensated heart failure (NYHA class III or IV), unstable angina pectoris, or myocardial infarction within the past 12 months.
• Uncontrolled Hypertension: Systolic blood pressure above 180 mmHg or diastolic blood pressure above 110 mmHg.
• Alcohol Use Disorder Medication: Use of medications for alcohol use disorder (e.g., disulfiram, naltrexone, acamprosate, nalmefene) within the 28 days prior to inclusion as recorded in the Timeline Followback (TLFB) schedule.
• Investigational Drugs: Receipt of any investigational drug within the past three months.
• Weight-Lowering Medications: Use of other weight-lowering pharmacotherapy in the past three months.
• Allergic Reactions: Hypersensitivity to the active substance or any of the excipients.
• Language Barriers: Inability to speak and/or understand Danish.
• Other Conditions: Any other condition that, in the investigator\'s opinion, may interfere with participation in the trial. For the subgroup of participants undergoing brain scans:
• MRI Contraindications: any contraindications for MRI (e.g., magnetic implants, pacemaker, claustrophobia).
• Benzodiazepine Use: Intermittent use of benzodiazepines within 12 days prior to the scanning session is not allowed. However, regular use of a stable dose of benzodiazepines is permitted.