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

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

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), approved for the treatment of type 2 diabetes and obesity, have shown promise as a novel treatment for alcohol use disorder (AUD). This study aims to investigate whether the Glucose-dependent Insulinotropic Polypeptide/GLP-1RA tirzepatide will reduce alcohol consumption in patients with a dual diagnosis of AUD and schizophrenia, a population in dire need of improved treatment options. To further investigate the neurobiological underpinnings of a potential dampening effect on alcohol consumption, functional magnetic resonance imaging (fMRI) brain scans will be applied.

The key anticipated outcomes include:

• decreased alcohol consumption and
• reduced alcohol cue-induced brain activity in the GIP/GLP-1-treated patient group compared with the placebo group. To the best of the investigators knowledge, this has never been examined before.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Dependence; Alcoholism; Schizophrenia; Alcohol Use Disorder; Schizophrenia and Schizophrenia Spectrum Psychosis; Schizophrenia Disorders; Schizophrenia and Disorders With Psychotic Features; Alcohol Abuse/Dependence
• Intervention / Treatment: Drug: Tirzepatide; Drug: Placebo

Detailed Description

The study is a randomised (1:1), double-blinded, placebo-controlled clinical trial including 26 weeks of treatment investigating whether tirzepatide vs placebo can reduce the number of heavy drinking days in patients with comorbid diagnoses of schizophrenia and AUD. The primary endpoint will be evaluated after 16 weeks of treatment. The study will conclude after a post-intervention follow-up 14 weeks after last treatment at week 40 of the study.

108 participants will be included. Alcohol consumption and secondary endpoints will be assessed at weeks 0, 4, 8, 12, 16, 20, 26, and 40, and all patients will be offered 6 sessions of supportive therapy, while participating in the study.

The randomisation and administration of the weekly injections (tirzepatide/placebo) will be administered by an unblinded staff not involved in other trial activities. All patients will be blindfolded when receiving the injections. Eligible patients (n=50) will have an fMRI brain scan performed at baseline and in week 16. Blood tests for safety measures and secondary endpoint-measures will be performed at weeks 0, 16, 26, and 40.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anders Fink-Jensen, MD, DMSc; Phone Number: +45 22755843; Email: anders.fink-jensen@regionh.dk
• Study Contact Backup: Name: Søren B Jensen, MD; Phone Number: +45 60294963; Email: soeren.broegger.jensen@regionh.dk

Study Locations

• Denmark
  • Denmark
    • Aalborg, Denmark, Denmark, 9000
      • Recruiting
      • Department of Psychiatry, Aalborg University Hospital
      • Contact: René E Nielsen, Chief Physician, Professor; Phone Number: +45 28 72 29 62; Email: ren@rn.dk
    • Frederiksberg, Denmark, Denmark, 2100
      • Recruiting
      • Psychiatric Center Copenhagen, Frederiksberg Hospital
      • Contact: Anders Fink-Jensen, MD, DMSc; Phone Number: +45 22755843; Email: anders.fink-jensen@regionh.dk
      • Contact: Søren B Jensen, MD, ph.d.-student; Phone Number: +45 60294963; Email: soeren.broegger.jensen@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

• Diagnosis:

  • Diagnosed with alcohol dependence according to the International Classification of Diseases, 10th Edition (ICD-10), and alcohol use disorder as per the Diagnostic 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 a consecutive 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 and the greatest number of heavy drinking days within the 28-day timeframe. This will be assessed using the Timeline Followback (TLFB) method. Heavy drinking days are defined as days with an alcohol intake of 4 or more units (48 g of alcohol) for women 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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirzepatide; Tirzepatide once-weekly s.c.titrated to a maximum dose of 15 mg	Drug: Tirzepatide; Once weekly injections s.c. with tirzepatide (Mounjaro(R)); Other Names: Mounjaro
Placebo Comparator: Placebo; Saline s.c. once-weekly	Drug: Placebo; Once weekly injections s.c. with placebo (BD Posiflush); Other Names: BD Posiflush (saline)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in heavy drinking days	The primary endpoint will be a change in alcohol consumption, measured as a per cent change in heavy drinking days after 16 weeks of treatment with tirzepatide or placebo, adjusted for the value at baseline (percentage points). Heavy drinking days will be registered using the Timeline-Follow-Back (TLFB) method including the last 21 consecutive days with the largest total alcohol intake and the greatest number of heavy drinking days within the 28 days preceding the evaluation. A heavy drinking day is defined as more than 60/48 grams (men/women) of alcohol in one day.	From baseline to 16 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total alcohol consumption	Change in total alcohol consumption measured using the TLFB method.	From baseline to 16 and 26 weeks of treatment and 14 weeks post-intervention
Days without alcohol consumption	Change in number of days without alcohol measured using the TLFB method.	From baseline to 16 and 26 weeks of treatment and 14 weeks post-intervention
World Health Organization (WHO) Risk Levels of Alcohol Consumption	Change in WHO alcohol risk level measured using the TLFB method.	From baseline to 16 and 26 weeks of treatment and 14 weeks post-intervention
Penn Alcohol Craving Scale (PACS) score	Change in Penn Alcohol Craving Scale (PACS) score. Minimum score = 0, maximum score =30. A high score means a worse outcome.	From baseline to 16 and 26 weeks of treatment
Alcohol Use Disorder Identification Test (AUDIT) score	Change in AUDIT score. Minimum score = 0, maximum score =40. A high score means a worse outcome.	From baseline to 16 and 26 weeks of treatment
Drug Use Disorders Identification Test (DUDIT) score	Change in DUDIT score. Minimum score = 0, maximum score =44. A high score means a worse outcome.	From baseline to 16 and 26 weeks of treatment
Drug use frequency	Change in drug use frequency measured using the drug use frequency section of the DUDIT-extended	From baseline to 16 and 26 weeks of treatment
Preferred substance of use	Change in preferred substance of use	From baseline to 16 and 26 weeks of treatment
Biomarkers of cannabis exposure	Changes in biomarkers of recent cannabis exposure (blood 11-hydroxy-delta 9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH) levels)	From baseline to 16 and 26 weeks of treatment
The Patient Health Questionnaire (PHQ-9)	Changes in PHQ-9	From baseline to 16 and 26 weeks of treatment
Fagerströms Test for Nicotine Dependence score	Changes in smoking habits using the Fagerströms Test for Nicotine Dependence score	From baseline to 16 and 26 weeks of treatment
Number of cigarettes smoked per day	Changes in average number of cigarettes smoked per day	From baseline to 16 and 26 weeks of treatment
Cotinine levels	Change in blood cotinine levels	From baseline to 16 and 26 weeks of treatment
Blood parameters	Changes in blood parameters (GGT, ALAT, MCV)	From baseline to 16 and 26 weeks of treatment
Blood phosphatidyl ethanol (PEth) levels	Changes in PEth levels	From baseline to 16 and 26 weeks of treatment and 14 weeks post-intervention
Glycaemic control parameters	Changes in HbA1c levels	From baseline to 16 and 26 weeks of treatment and 14 weeks post-intervention
Blood pressure	Change in blood pressure	From baseline to 16 and 26 weeks of treatment
Body weight	Change in body weight	From baseline to 16 and 26 weeks of treatment and 14 weeks post-intervention
Waist circumference	Change in waist circumference	From baseline to 16 and 26 weeks of treatment
fMRI alcohol cue-reactivity	Changes in fMRI BOLD signals in response to alcohol cues in brain regions related to reward in a subgroup (n=50) of participants	From baseline to 16 weeks of treatment
Global Assessment of Psychosocial Disability (GAPD)	Changes in GAPD score	From baseline to 26 weeks of treatment
Positive and Negative Syndrome Scale (PANSS-6)	Changes in symptom severity of schizophrenia measured using PANSS-6	From baseline to 26 weeks of treatment
Clinical Global Impression Severity Scale (CGI-S)	Changes in CGI-S score	From baseline to 26 weeks of treatment
Proteomics	Change in proteomics	From baseline to 16 and 26 weeks of treatment
WHO-5 Subjective Well-Being Index	Changes in quality of life measured using the World Health Organization-Five Well-Being Index (WHO-5)	From baseline to 26 weeks of treatment
Liver fibrosis (FIB-4 score)	Changes in FIB-4 score	From baseline to 26 weeks of treatment
Qualitative experience	For a subgroup of participants (n=20), qualitative interviews will be performed after 16 weeks of treatment to evaluate qualitative differences in trial participation experiences between the intervention and placebo groups, which will be assessed as a secondary outcome.	From baseline to 16 weeks of treatment
Heavy drinking days	Change in heavy drinking days measured using the TLFB method.	From baseline to 26 weeks of treatment and 14 weeks post-intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Outcome	Suicidal ideation measured using the Columbia Suicide Severity Rating Scale (C-SSRS)	From baseline to 16 and 26 weeks of treatment

Collaborators and Investigators

• Sponsor: Anders Fink-Jensen, MD, DMSci
• Investigators: Principal Investigator: Anders Fink-Jensen, MD, DMSc, Professor, Mental Healt h Service Centre Copenhagen , Frederiksberg Hospital, NP Lab

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 14, 2025
• First Submitted That Met QC Criteria: April 14, 2025
• First Posted (Actual): April 22, 2025

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: GLP-1; schizophrenia; alcohol; fMRI; dual diagnosis; GIP; Glucagon-like peptide 1; alcohol use disorder; Tirzepatide; Glucose-dependent Insulinotropic Polypeptide; Mounjaro(R)
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Schizophrenia; Alcoholism; Schizophrenia Spectrum and Other Psychotic Disorders; Amino Acids, Peptides, and Proteins; Proteins; Inorganic Chemicals; Chlorine Compounds; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Sodium Compounds; Chlorides; Hydrochloric Acid; Tirzepatide; Sodium Chloride
• Other Study ID Numbers: The DUALPSYCHIATRY study; U1111-1312-8134 (Registry Identifier: Universal Trial Number); 2024-518608-28-00 (Registry Identifier: EU CT NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be shared upon reasonable relevant requests, e.g. for meta-analyses or independent validations. IPD will be shared anonymized or de-identified to protect participants' privacy and in accordance with relevant regulations (GDPR).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No