Efficacy in Relapse Prevention: Psilocybin in Alcohol Use Disorder With Depressive Symptoms

Phase 3Not Yet RecruitingNCT07638553

Centre Hospitalier Universitaire de Nīmes172 enrolled

Overview

Up to 40% of individuals with alcohol use disorder (AUD) experience depression, which increases the risk of early relapse. Depression can cause relapse to occur 3 times faster in individuals with AUD who experience depressive symptoms at discharge. No treatments have been approved for individuals with both AUD and depression. Psilocybin, a psychedelic, shows promising results in treating both depression and addiction. It may be particularly effective for preventing relapse in people with AUD who also have depressive symptoms after detoxification, offering quicker action than traditional antidepressants. The Psilocybin Alcohol Depression (PAD) pilot study, launched in February 2024, has provided critical insights for avoiding methodological flaws and demonstrated that psilocybin-assisted psychotherapy (PAP) is both feasible and acceptable. Preliminary efficacy analyses were conducted: at 12 weeks, the 25 mg group showed significantly greater reductions in drinking days (p = 0.038) and craving frequency (p = 0.045). Relapse rates were 35% in the 25 mg group and 50% in the control group (HR = 0.52 \[0.16-1.65\]). In the ERPPAD trial, the study authors will compare high-dose PAP with low-dose PAP in preventing relapse in individuals with AUD and depressive symptoms. The hypothesis is that high-dose PAP will be more effective than low-dose in preventing relapse over 6 months.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

172

Conditions

Alcohol Use Disorder

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Confirmed DSM-5 diagnosis of severe AUD. * Scale BDI-II ((Beck Depression Inventory) ≥14 * The last drink must have been consumed between day(D) -60 and D -10 at the inclusion visit. The patient must have had at least 1 HDD during the last drinking period NB: The last drinking period before inclusion is defined by the last 4 weeks counted from the last drink. * The patient must have given their free and informed consent and signed the consent form * The patient must be a member or beneficiary of a health insurance plan Exclusion Criteria: * The subject is participating in an interventional study, a clinical trial, or a clinical investigation or is in a period of exclusion determined by a previous study * The subject refuses to sign the consent * It is impossible to give the subject informed information * The patient is under safeguard of justice or state guardianship * Patient unable to give informed consent. * Participants planning to donate sperm within three months of psilocybin administration * Positive pregnancy test at inclusion for participants of childbearing age. * Patient who is pregnant, breastfeeding, or wishing to become pregnant during participation in the study. * Any use of classical psychedelic in the last year * Other current substance use disorder (except tobacco) * Diagnosed schizophrenic or bipolar disorder * High emotional lability (clinician-judged) * On antipsychotics treatment that may interfere with psilocybin. * Need for monoamine oxidase inhibitor (MAOI) treatment, which may interfere with psilocybin. * Severe suicidal ideation (high risk on the Columbia scale) * 1st degree family member with a diagnosed psychotic disorder * Severe cognitive impairment (clinician-judged) * CIWA-AR \> 8 * Medical conditions that would preclude safe participation in the trial, for example: seizure disorders; significant impairment of hepatic function; coronary artery disease; history of arrhythmia; Abnormal QT interval prolongation (QTc \> 470 ms for women and \>450 ms for men); heart failure; uncontrolled hypertension (greater than 165/95 mmHg at screening); history of stroke; severe asthma; hyperthyroidism; narrow-angle glaucoma; stenosing gastroduodenal ulcer; pyloroduodenal obstruction; symptomatic prostatic hypertrophy or bladder neck obstruction; uncontrolled type I or type II diabetes, or a history of ketoacidosis, hyperglycemic coma, or severe hypoglycemia with loss of consciousness.

Locations (8)

Centre Hospitalier de la Côte Basque

Bayonne, France

CHU Besançon

Besançon, France

CHU de Bordeaux

Bordeaux, France

CHU Brest

Brest, France

CH Le Vinatier

Bron, France

CHU de Nantes

Nantes, France

CHU de Nîmes

Nîmes, France

CHU Saint-Etienne

Saint-Priest, France

Outcomes

Primary Outcomes

Incidence of relapse between groups

Relapse Yes/no, where relapse is defined as the 1st heavy drinking day, assessed using the Timeline Follow-Back (TLFB) method

Time frame: Month 6

Time to relapse between groups

Days until relapse, where relapse is defined as the 1st heavy drinking day, assessed using the Timeline Follow-Back (TLFB) method

Time frame: Month 6

Secondary Outcomes

Change in relapse rate between groups

Assessed using the Timeline Follow-Back (TLFB) method

Time frame: At weeks 3, 9, 15, 21, 27 compared to baseline

Change in rate of heavy drinking days between groups

Percent; Assessed using the Timeline Follow-Back (TLFB) method

Time frame: At weeks 3, 9, 15, 21, 27 compared to baseline

Change in total alcohol consumption between groups

Grams, assessed using the Timeline Follow-Back (TLFB) method

Time frame: At weeks 3, 9, 15, 21, 27 compared to baseline

Change in number of drinking days between groups

Days, assessed using the Timeline Follow-Back (TLFB) method

Time frame: At weeks 3, 9, 15, 21, 27 compared to baseline

Change in craving between groups

Assessed using the Craving Experience Questionnaire (CEQ), measuring strength and frequency of craving with a score ranging from 0 to 110, whereby a higher score denotes more craving.

Time frame: At weeks 3, 9, 15, 21, 27 compared to baseline

Change in alcohol-related quality of life between groups

Alcohol Quality of Life Scale- brief, a 7-item questionnaire assessing the negative impact of alcohol across 7 dimensions: social relationships, activities, living conditions, self-care, negative emotions, sleep, and loss of control.

Time frame: At weeks 3, 15, 21, 27 compared to baseline

Change in anxiety between groups

Beck Anxiety Inventory (BAI)

Time frame: At weeks 3, 9, 15, 21, 27 compared to baseline

Change in emotional dysregulation between groups

Difficulties in Emotion Regulation Scale (DERS), a 36-item questionnaire

Time frame: At weeks 3, 9, 15, 21, 27 compared to baseline

Change in rejection sensitivity between groups

Adult Rejection Sensitivity Questionnaire (A-RSQ)

Time frame: At weeks 3, 9, 15, 21, 27 compared to baseline

Change in post-Traumatic Stress Disorder between groups

Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5), where a score of 44 is highly sensitive to diagnose PTSD

Time frame: At weeks 3, 9, 15, 21, 27 compared to baseline

Visual Perspective task (VPT)

This task allows calculation of the egocentric bias index, the altercentric bias index and the egocentric egocentric bias

Time frame: Day 0

Visual Perspective task (VPT)

This task allows calculation of the egocentric bias index, the altercentric bias index and the egocentric egocentric bias

Time frame: Week 3

Visual Perspective task (VPT) for participants opting for a third dose

This task allows calculation of the egocentric bias index, the altercentric bias index and the egocentric egocentric bias

Time frame: Week 28

Request for a 3rd dose of psilocybin between groups

Yes/no

Time frame: Week 27

Reason for 3rd dose request

Relapse in AUD/ risk of relapse in AUD/low self-efficacy/ relapse in depression/ personal development/ other

Time frame: Week 27

Administration of 3rd dose

Yes/no

Time frame: Week 28

Relapse rate in relapsers between groups

Assessed using the Timeline Follow-Back (TLFB) method