The Trauma of Betrayal: Treating Adjustment Disorder With Reconsolidation Blockade Under Propranolol

Posttraumatic Stress Disorder Clinical Trial

Official title:

Treating Adjustment Disorders Stemming From Romantic Betrayals: An Open-label Trial of Impairing Memory Reconsolidation Using Propranolol

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03151681
• Other study ID #: PRPL-006
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: November 1, 2015
• Est. completion date: June 6, 2022

Study information

• Verified date: December 2022
• Source: Douglas Mental Health University Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Attachment injuries are events occurring within couple relationships that involve betrayal or abandonment by a significant other during times of need (e.g., infidelity). They can be understood as relationship traumas, which can lead to debilitating symptoms consistent with posttraumatic stress disorder (PTSD), depression, and generalized anxiety for the injured partner. Research has demonstrated that the presence of an attachment injury represents a barrier to empirically effective couple's therapy. However, disrupting memory reconsolidation with the beta-blocker propranolol has been shown to alleviate PTSD symptoms by attenuating the salience of the emotional trauma memory, representing an interesting avenue for the treatment of adjustment disorders stemming from attachment injuries. Moreover, evidence suggests that a certain degree of mismatch, or an error between what is expected/predicted to occur and what actually occurs, must be present in order for a memory to destabilize and enter the reconsolidation phase following retrieval. Here, the investigators aim to extend the conditions under which reconsolidation therapy with propranolol can be used in a clinical setting, as well as assess whether incorporating mismatch enhances treatment effects. The investigators hypothesize that, compared to a wait-list control, 4-6 sessions of memory reactivation under propranolol will significantly reduce trauma-related and general anxio-depressive symptoms, associated with an attachment injury. Moreover, the investigators hypothesize that participants randomized to the mismatch group will improve significantly more than the standard treatment group on all variables of interest.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: June 6, 2022
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Diagnosis of an adjustment disorder or chronic adjustment disorder, as defined by the Diagnostic and Statistical Manual for Mental Disorders, as a result of an attachment injury, defined as an event involving the perceived betrayal, violation of trust, or abandonment by a significant other.
• Currently experiencing clinically important psychological distress as a result of the event, as defined by a score of at least 22 on the IES-R, and a score of at least "moderately ill" on the Clinical Global Impressions - Severity of Illness Scale.
• Must have been in the romantic relationship for at least 6 months prior to the event.
• Must not take psychotropic medication.
• Fluency in English or French

Exclusion Criteria:

• Systolic blood pressure <100 mm Hg;
• Cardiac rhythm below 55 beats per minute;
• A medical condition that contraindicates the administration of propranolol, e.g., Asthma, chronic obstructive pulmonary disease, cardiac insufficiency, cardiac choc, Second- or third-degree atrioventricular block, diabetes, spastic angina, auricular sinus illness, bradycardia, Raynaud's disease, severe peripheral vascular disease, untreated Pheochromocytoma, arterial hypotension, previous anaphylactic allergic shock;
• Previous adverse reaction to, or non-compliance with, beta-blocker;
• Current use of a substance that may involve potentially dangerous interactions with propranolol, including P450 2D6 inhibitors.
• Women who are pregnant or breast feeding;
• Individuals currently participating in any other form of psychotherapy (other than strictly supportive).
• History of substance dependence disorder, bipolar disorder, or psychotic disorder;
• Participants judged (based on history, mental status exam, clinical impression, or the Suicidal Behaviors Questionnaire as being at significant risk of suicidal behavior.
• Participation in another drug trial within 30 days prior to the screening visit
• Presence of any clinical condition that might interfere with the interpretation of the efficacy and safety results.

Related Conditions & MeSH terms

• Adjustment Disorders
• Disease
• Posttraumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Trauma and Stressor Related Disorders

Intervention

Drug:
• Propranolol Pill
1mg/kg of propranolol 60 minutes prior to memory reactivation

Locations

Country	Name	City	State
Canada	Douglas Mental Health University Institute	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Douglas Mental Health University Institute

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Lonergan M, Saumier D, Pigeon S, Etienne PE, Brunet A. Treatment of adjustment disorder stemming from romantic betrayal using memory reactivation under propranolol: A open-label interrupted time series trial. J Affect Disord. 2022 Nov 15;317:98-106. doi: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Within-group difference: Wait-list vs. Treatment; Between-group difference: Mismatch vs. No Mismatch on Impact of Events Scale-Revised	Severity of Trauma and Stressor-related symptoms	Administered at baseline (Week 0), Post-Wait-list (Week 4), at each subsequent weekly visit, at the one-week post-treatment follow-up, and at the three-month follow up.
Secondary	Within-group difference: Wait-list vs. Treatment; Between-group difference: Mismatch vs. No Mismatch on Hopkins Symptom Checklist-25	General Psychological Distress (Depression and Anxiety)	Administered at baseline (Week 0), Post-Wait-list (Week 4), at each subsequent weekly visit, at the one-week post-treatment follow-up, and at the three-month follow up.
Secondary	Within-group difference: Wait-list vs. Treatment; Between-group difference: Mismatch vs. No Mismatch on World Health Organization - Quality of Life BREF	Perceived Quality of Life in 4 Domains, Psychological, Physical, Environmental, Social	Administered at baseline (Week 0), Post-Wait-list (Week 4), at the one-week post-treatment follow-up, and at the three-month follow up.