Individuals with PTSD often wish to rid themselves of traumatic memories. Traumatic memories, commonly retrieved or reactivated in treatment, enter a malleable state. Once an individual stops thinking about a memory, the memory returns to a stable form, a process known as reconsolidation. It had been thought that traumatic memories lasted indefinitely and the most that could be hoped for was to inhibit their expression through extinction. Recent research has shown that even after a traumatic memory has consolidated, its retrieval-when influenced by certain medications- may result in permanent weakening or elimination. Therefore, medications that interfere with the reconsolidation process could potentially weaken or eliminate retrieved traumatic memories. Propranolol, a beta blocker, is one medication that has been studied in animals and humans. This randomized clinical trial in 60 adults with longstanding PTSD demonstrated that the administration of Propranolol before recall of a traumatic event significantly reduced PTSD symptoms over six weeks. The effect sizes obtained in this study compare favorably to those obtained with other major evidence-based treatments for PTSD such as Cognitive-Behavioral Therapy (CBT) and Selective Serotonin Reuptake Inhibitor (SSRI) medications. If these results can be replicated in further studies, administration of Propranolol prior to reactivation of traumatic memories may become a new therapy for some patients with PTSD.

 

Propranolol & PTSD

 

Propranolol, also known as Inderal, inhibits the actions of the neurotransmitter, norepinephrine. Norepinephrine has been shown to enhance memory consolidation.   Propranalol has a wide variety of medical uses including management of hypertension, irregular heart rhythms, tremors and migraine headaches. Psychiatrists have used it mainly in the treatment of performance anxiety but also in the treatment of specific phobias,  such as fear of spiders, dental fear , and social phobia  (Steenen et al. 2015). Because Propranolol inhibits norepinephrine, Propranolol has been studied as a potential treatment for PTSD (Brunet et al. 2008; Brunet at al. 2011). Therapies for PTSD necessarily involve recall, reexperiencing and reconsolidation of traumatic memories. Therapies that include a prolonged reexperiencing component often have a high drop-out rate, and the effects may decay over time (Mello et al. 2013; Bisson et al. 2013). There is therefore a need to find ways to impact the reconsolidation process so that traumatic memories are weakened or eliminated, and, hopefully, PTSD symptoms improve. Because Propranolol inhibits norepinephrine and, by extension, memory consolidation, it has recently been studied in PTSD. Several open label studies of Propranolol in PTSD demonstrated a reduction in PTSD symptoms which were maintained over time (Brunet et al. 2011; Brunet et al. 2014; Kindt & van Emmerik 2016). This study is the first double-blind, randomized controlled clinical trial of Propranolol as an intervention for PTSD.

 

The Study

 

Design

(1)    Subjects were recruited through referral and local advertisement to participate at McGill University in in Montreal.

(2)    Adults with PTSD for at least 6 months who had a score of > 44 on the PTSD Checklist-Specific (PCL-S) were eligible. Exclusion criteria included medical issues that made administration of Propranolol unsafe or that made interpreting the results confusing including a history of psychotic disorder, bipolar disorder or traumatic brain injury; current substance dependence; acute suicidal ideation; strong dissociative symptoms or current engagement in an evidence-based therapy for PTSD.

(3)    Assessment measures included the PCL-S, the Clinician Administered PTSD Scale (CAPS) and the Mini International Neuropsychiatric Interview.

(4)    Subjects were given a combination of short acting and long acting Propranolol. Short acting Propranolol reaches a peak concentration after about one hour; long acting Propranolol achieves steady levels for 24 hours.

(5)    60 subjects were randomized into 2 groups: 30 subjects received active treatment with Propranolol and the other 30 subjects received placebo.

(6)    One hour after ingesting medication each group was asked to write and then read aloud a one-page trauma narrative "as if they were back in the event." The narrative was supposed to focus on the event's most disturbing moments and include 5 or more bodily sensations chosen from a checklist. On subsequent visits, each participant was asked if they wished to rectify or supplement the narrative, and they were asked read the narrative aloud again.

 

Results

(1)    Participants in the Propranolol and placebo groups did not differ on sociodemographic variables and had similar pretreatment CAPS and PCL-S scores.

(2)    At the posttreatment assessment, CAPS scores decreased in both groups but the decreases were significantly greater in the Propranolol group (p<0.034). The intention to treat and pre- to posttreatment CAPS improvements were 38% and 36% in the Propranolol group and 24% and 13% in the placebo group .

(3)    PCL-S scores also decreased significantly in the Propranolol group (p<0.001). The intention to treat and pre- to posttreatment PCL-S improvements were 56% and 53% in the Propranolol group and 15% and 10% in the placebo group

(4)    The PCL-S time-by-group interaction decreased on average 2.43 points per week for a total significant difference of 14.58 points above placebo .

(5)    There was a marked pre- to posttreatment effect size with 2.74 for Propranolol and 0.55 for placebo.

(6)    This was a relatively short study, but six month follow-up showed that participants in the Propranolol group continued to have lower scores than the placebo group, even without the use of Propranolol. This finding should be interpreted with caution since only about half of the participants in each group were available for this follow-up study.

 

Implications for Practice

 

Preventing the deleterious and often chronic effects of trauma is important to clinicians. This study demonstrates that PTSD subjects who recalled their traumatic event while taking Propranolol showed a decrease in symptoms, both by their own report and by that of their clinicians. This significant difference held in subjects who did not attend all the sessions or in whom protocol deviations existed. The effect sizes for Propranolol compare to the best evidence-based treatments for PTSD including CBT and SSRIs. This study needs to be replicated, but if the results hold, Propranolol used during memory reconsolidation may be useful for some patients with PTSD.