Propranolol for PTSD and Alcoholism

Overseen by Ahmed Hassan, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Centre for Addiction and Mental Health

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This study evaluates the therapeutic tolerability of the use of Cognitive Processing Therapy (CPT) with propranolol in participants with Posttraumatic Stress Disorder (PTSD) and Alcohol Use Disorder (AUD). The investigators are planning to perform an initial proof -of- concept randomized, placebo- controlled trial evaluating propranolol in participants with PTSD and AUD starting CPT for 12 weeks with three post-treatment follow ups at week-16, week-20, and week-24. Participants with current diagnosis of PTSD and AUD seeking treatment will be randomized to either a propranolol group (n=24) or placebo group (n=24) after enrollment. All participants will receive CPT for 12 weeks after randomization. Primary outcomes will be measured in both groups at the end of the study (week 12).

Do I have to stop taking my current medications for the trial?

The trial requires participants to be on an antidepressant for PTSD. You cannot start new therapies or anti-craving medications during the trial unless you've been on them for at least 6 months. The protocol does not specify stopping other medications, but you cannot use medications that interact with propranolol, like anti-arrhythmic drugs or calcium channel blockers.

What data supports the idea that Propranolol for PTSD and Alcoholism is an effective drug?

The available research shows mixed results for the effectiveness of Propranolol in treating PTSD and alcoholism. In one case study, a woman with severe PTSD symptoms experienced a rapid reduction in symptoms after taking Propranolol following a traumatic event. However, a larger study found that Propranolol did not significantly outperform a placebo in reducing PTSD symptoms over a six-week period, although it showed some benefits for patients with severe symptoms. For alcoholism, Propranolol was found to help calm patients during withdrawal and was more effective than another medication, diazepam, in reducing tension symptoms. Overall, while there are some positive findings, the evidence is not strong enough to conclusively support Propranolol as an effective treatment for PTSD and alcoholism. ^{1 2 3 4 5}

What safety data exists for propranolol in treating PTSD and alcoholism?

The available studies on propranolol primarily focus on its use for anxiety disorders and PTSD. A systematic review found insufficient evidence to support its routine use for anxiety disorders, including PTSD. A controlled study showed propranolol was effective in reducing panic attacks, but with a slower onset compared to alprazolam. A case study reported rapid reduction of PTSD symptoms with propranolol after a traumatic event. No significant safety concerns were highlighted in these studies, but further research is suggested. No specific data on alcoholism treatment was found. ^{1 2 4 6 7}

Is the drug Propranolol promising for treating PTSD and Alcoholism?

Propranolol shows promise in reducing alcohol consumption and may help with PTSD symptoms by blocking memory reconsolidation. It has been effective in some studies for reducing panic attacks and avoidance behavior, suggesting potential benefits for PTSD and alcoholism. ^{1 2 6 8 9}

Research Team

Ahmed Hassan, MD

Principal Investigator

CAMH

Eligibility Criteria

Adults aged 18-70 with PTSD and AUD, who speak English, have had recent heavy drinking episodes, are on antidepressants for PTSD, and agree to use contraception if applicable. Excluded are those with severe medical conditions or contraindications to propranolol, pregnant/breastfeeding women, high suicide risk individuals, users of certain drugs conflicting with the trial medication.

Inclusion Criteria

Has a minimum of two episodes of heavy drinking in the past 30 days

I am between 18 and 70 years old.

I have been diagnosed with PTSD by a professional using the CAPS-5.

Exclusion Criteria

Pregnant or breastfeeding women

Basal systolic blood pressure < 100 mm Hg or basal heart rate < 55 beats/minute

I do not have a severe illness that makes it unsafe for me to join the study.

Treatment Details

Interventions

• Placebo (Drug)
• Propranolol (Beta Blocker)

Trial Overview The study is testing whether Cognitive Processing Therapy (CPT) combined with propranolol is tolerable and effective for treating people with both PTSD and AUD compared to a placebo group. Each participant will undergo CPT for 12 weeks and be assessed up until week 24.

Participant Groups

Group I: Propranolol Experimental Treatment 1 Intervention

Medication treatment regimen will consist of 12 weeks of 40 mg immediate-release propranolol BID

Group II: Placebo Placebo Group 1 Intervention

Matching placebo will be administered BID for 12 weeks

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Findings from Research

A systematic review of eight studies involving 302 participants found that propranolol did not show significant efficacy compared to placebo or benzodiazepines in treating anxiety disorders, including panic disorder and PTSD.

The evidence is currently insufficient to recommend propranolol as a routine treatment for anxiety disorders, as it did not demonstrate a clear benefit in alleviating symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis. Steenen, SA., van Wijk, AJ., van der Heijden, GJ., et al.[2022]

In a study involving 52 patients with dental anxiety, perioperative propranolol did not significantly reduce dental anxiety compared to a placebo, indicating it may not be effective for this specific type of fear.

Both the propranolol and placebo groups showed a decrease in dental anxiety over time, but the lack of significant difference suggests that propranolol does not provide additional benefits for patients with dental phobia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative Propranolol Against Dental Anxiety: A Randomized Controlled Trial. Steenen, SA., Su, N., van Westrhenen, R., et al.[2022]

In a study of 66 adults with longstanding PTSD, both propranolol and placebo led to significant reductions in PTSD and depression symptoms during treatment, but there was no significant difference between the two groups.

However, for patients with severe PTSD symptoms, those treated with propranolol showed continued improvement in symptoms three months after treatment, while those on placebo experienced a worsening, suggesting that propranolol may have long-term benefits for certain individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Traumatic memory reactivation with or without propranolol for PTSD and comorbid MD symptoms: a randomised clinical trial. Roullet, P., Vaiva, G., Véry, E., et al.[2021]

A 44-year-old woman with severe PTSD symptoms from multiple motor vehicle accidents showed rapid improvement after starting propranolol (60 mg twice daily) just 48 hours post-trauma, with her PTSD rating score dropping significantly from 86 to 56 within 11 days.

This case suggests that propranolol may be effective in preventing or reducing reemergent PTSD symptoms, marking a novel application for this medication in trauma-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol for reemergent posttraumatic stress disorder following an event of retraumatization: a case study. Taylor, F., Cahill, L.[2013]

In patients undergoing withdrawal from chronic alcoholism, propranolol effectively normalizes increased cardiac output and reduces peripheral vascular resistance, leading to a calming effect, as observed in a double-blind study.

Propranolol was found to be more effective than diazepam in alleviating symptoms of psychic tension associated with alcohol withdrawal, with minimal side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol in the treatment of alchoholism: a review. Carlsson, C.[2013]

In a 6-week study involving 29 patients with agoraphobia and panic disorder, both propranolol and alprazolam were effective in reducing panic attacks and avoidance behavior.

Alprazolam showed a faster onset of its effects compared to propranolol, suggesting that while both medications work, propranolol may need further investigation to fully understand its potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled study of alprazolam and propranolol in panic-disordered and agoraphobic outpatients. Ravaris, CL., Friedman, MJ., Hauri, PJ., et al.[2013]

A study involving six healthy adult volunteers tested four different brands of propranolol (Inderal, Ciplar, Corbeta, and Propal) to assess variations in how the body absorbs and responds to the medication.

The results showed no significant differences in the pharmacokinetic (how the drug is processed in the body) and pharmacodynamic (the drug's effects on the body) parameters among the brands, indicating they are likely interchangeable in terms of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. Biswas, NR., Garg, SK., Kumar, N., et al.[2013]

In a 6-week clinical trial involving 60 adults with long-standing PTSD, propranolol significantly reduced PTSD symptoms compared to a placebo, with a notable effect size of 1.76 for the Clinician-Administered PTSD Scale (CAPS).

The study suggests that administering propranolol before trauma memory reactivation sessions is an effective treatment strategy for PTSD, indicating its potential as a novel therapeutic approach based on reconsolidation theory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of PTSD Symptoms With Pre-Reactivation Propranolol Therapy: A Randomized Controlled Trial. Brunet, A., Saumier, D., Liu, A., et al.[2019]

In a study using male Wistar rats, the β1/2 adrenergic receptor antagonist propranolol significantly reduced alcohol drinking, particularly showing a trend towards greater impact on compulsion-like alcohol drinking (CLAD) compared to alcohol-only drinking (AOD).

While propranolol and betaxolol showed potential in decreasing alcohol consumption, they may also cause undesirable side effects, and their effects on specific brain areas related to drinking did not yield expected results, suggesting a complex role of the noradrenergic system in alcohol use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of beta- and alpha-adrenergic receptors on alcohol drinking. De Oliveira Sergio, T., Wean, S., Katner, SN., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Perioperative Propranolol Against Dental Anxiety: A Randomized Controlled Trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Traumatic memory reactivation with or without propranolol for PTSD and comorbid MD symptoms: a randomised clinical trial. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Propranolol for reemergent posttraumatic stress disorder following an event of retraumatization: a case study. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Propranolol in the treatment of alchoholism: a review. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

A controlled study of alprazolam and propranolol in panic-disordered and agoraphobic outpatients. [2013]

7. Germany pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Reduction of PTSD Symptoms With Pre-Reactivation Propranolol Therapy: A Randomized Controlled Trial. [2019]

9. England pubmed.ncbi.nlm.nih.gov

The role of beta- and alpha-adrenergic receptors on alcohol drinking. [2023]