Prazosin for Alcohol Withdrawal

Overseen By RAJITA SINHA, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Opioids, Anticonvulsants, Antidepressants, others

Disqualifiers: Substance use disorders, Psychotic disorders, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Prazosin, a medication, can reduce alcohol withdrawal symptoms in individuals with Alcohol Use Disorder (AUD). Participants will receive either Prazosin or a placebo for 12 weeks, along with weekly behavioral counseling to support recovery. Researchers aim to determine if Prazosin can decrease heavy drinking days and improve symptoms such as craving, mood, anxiety, and sleep issues. The trial suits individuals who regularly drink alcohol, experience withdrawal symptoms, and currently meet criteria for moderate to severe AUD. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. The trial excludes people who regularly use anticonvulsants, sedatives, certain pain relievers, and other specific medications. It's important to discuss your current medications with the trial team to see if you qualify.

Is there any evidence suggesting that Prazosin is likely to be safe for humans?

Research has shown that prazosin is generally well-tolerated by people with alcohol use disorder (AUD). It can help reduce alcohol consumption, particularly for those experiencing withdrawal symptoms. Some participants reported side effects like dizziness and tiredness while taking prazosin, but these were usually mild.

Prazosin is not a new medication; it is already approved for treating high blood pressure, which provides some confidence about its safety in humans. Previous studies on alcohol use disorder have not shown strong evidence of major negative effects from prazosin. This suggests it is relatively safe for people with AUD, but as with any medication, individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Prazosin is unique because it offers a new approach to treating alcohol withdrawal by targeting the brain's adrenergic system, which is different from the traditional use of benzodiazepines like diazepam or lorazepam. This mechanism may help reduce withdrawal symptoms like anxiety and agitation more effectively. Researchers are excited about prazosin because it has the potential to offer a safer, non-addictive alternative that could complement or even replace current treatments, providing a new avenue for patients struggling with alcohol dependence.

What evidence suggests that Prazosin might be an effective treatment for Alcohol Use Disorder?

Studies have shown that prazosin, a medication commonly used for high blood pressure, can help people with alcohol use disorder (AUD) reduce or stop drinking. It is particularly effective for those who have experienced alcohol withdrawal symptoms. Research indicates that prazosin works well for individuals with mild withdrawal symptoms, helping them reduce the number of days they drink heavily. Initial findings suggest that this drug can lessen cravings and improve mood, anxiety, and sleep issues related to AUD. In this trial, participants will receive either prazosin or a placebo to evaluate its effectiveness in managing alcohol withdrawal symptoms and supporting recovery in individuals with AUD. ^{2 4 6 7 8}

Who Is on the Research Team?

Gretchen Hermes, MD

Principal Investigator

Yale University

David Fiellin, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals with moderate to severe Alcohol Use Disorder who experience withdrawal symptoms. Participants must be able to read English, have no other substance use disorders (except nicotine), and not be using certain medications like opioids or antihypertensives. They should not have severe psychiatric conditions or significant medical issues that could interfere with the study.

Inclusion Criteria

Must meet current DSM-5 criteria for moderate to severe Alcohol Use Disorder (AUD) using SCID-I for DSM-5;

Able to read English and complete study evaluations

Able to provide informed written and verbal consent

Exclusion Criteria

I do not have a severe mental health condition that needs specific treatment or medication.

Meet current criteria for moderate to severe substance use disorders from use of any another psychoactive substance, excluding nicotine

Women who are pregnant, nursing or refuse to use a reliable form of birth control (as assessed by pregnancy tests during initial medical evaluation, and assessed every two weeks during the course of the study)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Prazosin or Placebo over a 12-week period with a 2-week titration and a 5-day taper, along with weekly behavioral counseling

12 weeks

2 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with assessments at 1 and 3 months post-treatment

3 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• 12-Step Facilitation with Relapse Prevention and Contingency Management
• Prazosin

Trial Overview The trial tests Prazosin (16mg/day) against a placebo over 12 weeks in patients with Alcohol Use Disorder and withdrawal symptoms. It includes weekly behavioral counseling sessions. The main focus is on reducing heavy drinking days, along with monitoring craving, mood, anxiety, and sleep problems.

How Is the Trial Designed?

Group I: Active Drug Experimental Treatment 2 Interventions

Prazosin (16mg/day) versus Placebo comparator, administered in t.i.d schedule, in capsules, over a 12 week period, with 2 weeks titration in weeks 1-2 and a 5-day taper in week 12.

Group II: Placebo Drug Placebo Group 1 Intervention

Placebo for 12 weeks.

Prazosin is already approved in United States for the following indications:

Approved in United States as Minipress for:

• Hypertension
• Benign prostatic hypertrophy
• Posttraumatic stress disorder (PTSD) nightmares and hyperarousal symptoms

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

A case study highlights the severe challenges of alcohol withdrawal in hospitalized patients, exemplified by a patient with delirium tremens who required an extremely high dose of 1,600 mg/day of lorazepam for management.

The discussion includes alternative treatments for alcohol withdrawal, suggesting that there are various approaches to consider beyond high-dose benzodiazepines like lorazepam.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of alcohol withdrawal requiring 1,600 mg of lorazepam in 24 hours. Kahn, DR., Barnhorst, AV., Bourgeois, JA.[2019]

A recent randomized controlled trial with 100 participants found that prazosin, an α1 adrenoceptor antagonist, significantly reduced drinking days and heavy drinking days in patients with high alcohol withdrawal symptoms (AWS), specifically those with a Clinical Institute Withdrawal Assessment for Alcohol-Revised score of 3 or higher.

The study suggests that targeting high AWS with symptom-driven pharmacological interventions like prazosin may improve treatment outcomes for individuals with alcohol use disorder, although the mixed results from previous trials indicate the need for further research on various medications that could be more effective or better tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prazosin for Alcohol Use Disorder: A Symptom-Driven Approach to the Choice of Intervention. Andrade, C.[2021]

In a 12-week study involving 100 adults with alcohol dependence, prazosin significantly reduced heavy drinking days and overall drinking days in participants with high alcohol withdrawal symptoms, compared to those on a placebo.

Prazosin also improved associated symptoms like anxiety, depression, and alcohol craving in individuals experiencing high withdrawal symptoms, suggesting that these symptoms may predict the treatment's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderation of Prazosin's Efficacy by Alcohol Withdrawal Symptoms. Sinha, R., Wemm, S., Fogelman, N., et al.[2022]

In a double-blind study, patients treated with clonidine experienced a recovery from moderately severe alcohol withdrawal symptoms about one day faster than those receiving a placebo, indicating its efficacy in this context.

Clonidine significantly improved symptoms such as tremor, sweating, and anxiety without causing significant side effects, making it a useful alternative for managing alcohol withdrawal while minimizing the use of tranquilizers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clonidine in alcohol withdrawal. Björkqvist, SE.[2019]

In a study involving 19 patients with acute alcohol withdrawal, intramuscular administration of lorazepam led to a rapid decrease in the severity of withdrawal symptoms.

The results suggest that lorazepam is effective for managing alcohol withdrawal symptoms, indicating a need for larger trials to further evaluate its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of injectable lorazepam in alcohol withdrawal. Spencer, J.[2021]

Prazosin significantly reduces the motivation to seek and consume alcohol in alcohol-preferring rats, indicating its potential as a treatment for alcohol dependence.

The study found that prazosin specifically decreases alcohol-seeking behavior without affecting sucrose-seeking, suggesting its effects are not due to general motor impairment or malaise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of prazosin, an α1-adrenergic receptor antagonist, on the seeking and intake of alcohol and sucrose in alcohol-preferring (P) rats. Verplaetse, TL., Rasmussen, DD., Froehlich, JC., et al.[2021]

In a study of 10 Japanese men with mild hypertension, alcohol consumption significantly decreased blood pressure (BP) for several hours, while treatment with the alpha1-blocker prazosin further enhanced this hypotensive effect.

The findings suggest that combining alcohol with alpha1-blockers like prazosin can lead to a marked reduction in BP, indicating a potential safety concern for hypertensive patients using these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction of alcohol and an alpha1-blocker on ambulatory blood pressure in patients with essential hypertension. Kawano, Y., Abe, H., Kojima, S., et al.[2019]

Prazosin effectively prevents the alcohol deprivation effect (ADE) in alcohol-preferring rats, indicating its potential to reduce relapse in alcohol consumption after periods of abstinence.

In a study involving adult male P rats, prazosin administration abolished the expected increase in alcohol intake following alcohol deprivation, suggesting it may be a promising treatment for preventing relapse in individuals with alcohol use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prazosin Reduces Alcohol Intake in an Animal Model of Alcohol Relapse. Froehlich, JC., Hausauer, B., Fischer, S., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33207935/

Moderation of Prazosin's Efficacy by Alcohol Withdrawal ... The findings indicate that alcohol withdrawal symptoms are a significant moderator of prazosin treatment response for alcohol use outcomes ...

2. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.2020.20050609

Moderation of Prazosin's Efficacy by Alcohol Withdrawal ... The findings indicate that alcohol withdrawal symptoms are a significant moderator of prazosin treatment response for alcohol use outcomes.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04793685

Prazosin for Alcohol Use Disorder With Withdrawal ... This is a Phase 2 single site randomized clinical trial (RCT) to be supported by a new NIH-NIAAA grant, R01-AA029113-01, to assess the efficacy of Prazosin ...

4. mesudlearningcommunity.org mesudlearningcommunity.org/wp-content/uploads/2023/11/Effectiveness-of-Prazosin-in-AUD-Study-11.2023.pdf

Effectiveness of Prazosin in AUD Study Title: Prazosin may reduce drinking in study volunteers with AUD who had mild alcohol withdrawal symptoms compared to those with no alcohol withdrawal. Citation ...

5. addictionpolicy.org addictionpolicy.org/post/a-new-medication-assisted-treatments-for-alcohol-use-disorders-prazosin-in-the-treatment-of-auds

A New Medication-Assisted Treatment for Alcohol Use ... New research shows that it can help patients with alcohol use disorders, alcoholics, who have alcohol withdrawal symptoms reduce or eliminate their drinking.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8119326/

Moderation of Prazosin's Efficacy by Alcohol Withdrawal ... The authors examined whether alcohol withdrawal symptoms moderate the efficacy of prazosin in reducing alcohol intake and associated secondary outcomes.

7. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.2018.18091022

Prazosin for the Treatment of Alcohol Use Disorders ... withdrawal-related alcohol intake. Future studies may benefit from specifically assessing alcohol withdrawal symptoms to target withdrawal ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10939766/

Effects of prazosin treatment on liver enzymes are moderated ... Alcohol use disorder (AUD) is associated with significant liver pathology marked by elevated liver enzymes. Prazosin, an alpha1-noradrenergic antagonist ...