Effects of Tirzepatide on Alcohol Intake in Patients Diagnosed With Schizophrenia and Alcohol Use Disorder

Inclusion Criteria:

• Informed Consent: The patient must provide both oral and written informed consent.

• Diagnosis:

• Diagnosed with alcohol dependence according to the International Classificationof Diseases, 10th Edition (ICD-10), and alcohol use disorder as per theDiagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).

• Diagnosed with schizophrenia spectrum disorder according to ICD-10 and DSM-5

• AUDIT Score: Alcohol Use Disorder Identification Test (AUDIT) score greater than 15.

• Body Mass Index (BMI): BMI of 23 kg/m² or higher.

• Age Range: Between 18 and 70 years old (inclusive).

• Heavy Alcohol Consumption: Defined as 4 or more heavy drinking days within aconsecutive 21-day period during the 28 days preceding the baseline evaluation. The 21-day period will be selected based on the largest total alcohol consumption andthe greatest number of heavy drinking days within the 28-day timeframe. This will beassessed using the Timeline Followback (TLFB) method. Heavy drinking days aredefined as days with an alcohol intake of 4 or more units (48 g of alcohol) forwomen and 5 or more units (60 g of alcohol) for men.

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 7on the Clinical Global Impression-Severity (CGI-S) scale.

• Coercive Measures: Current use of coercive measures, which includes individualssentenced to treatment ('dom til behandling').

• Suicidal Behaviour: Evidence of current severe suicidal behaviour, as assessed bythe investigator during clinical evaluation.

• History of Severe Alcohol Withdrawal: History of delirium tremens or alcoholwithdrawal seizures.

• Severe Withdrawal Symptoms: Clinical Institute Withdrawal Assessment of AlcoholScale, revised (CIWA-Ar) score greater than 9 at baseline examination.

• Severe Neurological Conditions: Presence of severe neurological diseases, includingsevere 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 treatmentplus two months after discontinuation of semaglutide), or are not using a highlyeffective contraceptive method throughout the study period. Highly effective methodsinclude 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 humanchorionic gonadotropin (hCG) level greater than 3 U/L at inclusion will also beexcluded.

• Liver Function: Impaired hepatic function, defined as liver transaminases greaterthan three times the upper limit of normal.

• Renal Function: Impaired renal function, indicated by an estimated glomerularfiltration 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 morethan twice the upper limit of normal.

• Thyroid Conditions: Previous medullary thyroid carcinoma (MTC) or a family historyof MTC and/or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

• Cardiac Issues: Decompensated heart failure (NYHA class III or IV), unstable anginapectoris, or myocardial infarction within the past 12 months.

• Uncontrolled Hypertension: Systolic blood pressure above 180 mmHg or diastolic bloodpressure 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 toinclusion as recorded in the Timeline Followback (TLFB) schedule.

• Investigational Drugs: Receipt of any investigational drug within the past threemonths.

• Weight-Lowering Medications: Use of other weight-lowering pharmacotherapy in thepast three months.

• Allergic Reactions: Hypersensitivity to the active substance or any of theexcipients.

• Language Barriers: Inability to speak and/or understand Danish.

• Other Conditions: Any other condition that, in the investigator's opinion, mayinterfere 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 thescanning session is not allowed. However, regular use of a stable dose ofbenzodiazepines is permitted.