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

Abstract

Post-traumatic stress disorder (PTSD) is difficult to treat but one promising strategy is to block memory reconsolidation of the traumatic event. This study aimed to evaluate the efficacy of traumatic memory reactivation under the influence of propranolol, a noradrenergic beta-receptor blocker, in reducing PTSD symptoms as well as comorbid major depression (MD) symptoms. We conducted a double blind, placebo-controlled, randomised clinical trial in 66 adults diagnosed with longstanding PTSD. Propranolol or a placebo was administered 90 min before a brief memory reactivation session, once a week for 6 consecutive weeks. Measures included the SCID PTSD module, the PTSD Check List (PCL-S) and the Beck Depression Inventory-II (BDI-II). PTSD symptoms decreased both in the pre-reactivation propranolol group (39.28%) and the pre-reactivation placebo group (34.48 %). During the 6 treatment sessions, PCL-S and BDI-II scores decreased to similar extent in both groups and there were no treatment differences. During the 3-month follow-up period, there were no treatment effects for the mean PCL-S and BDI-II scores. However, in patients with severe PTSD symptoms (PCL-S ≥ 65) before treatment, PCL-S and BDI-II scores continued to decline 3 months after the end of treatment in the propranolol group while they increased in the placebo group. Repeated traumatic memory reactivation seemed to be effective for PTSD and comorbid MD symptoms. However, the efficacy of propranolol was not greater than that of placebo 1 week post treatment. Furthermore, in this traumatic memory reactivation, PTSD symptom severity at baseline might have influenced the post-treatment effect of propranolol.

Intrusive experiences in posttraumatic stress disorder: Treatment response induces changes in the directed functional connectivity of the anterior insula

“…This trial received approval from an ethics committee (CPP 2009-012976-29) and was registered on clinicaltrials.gov (NCT01713556). The main results for this clinical trial (i.e., that the efficacy of propranolol was not greater than that of placebo one week posttreatment) are presented elsewhere ( Roullet et al, 2021 ).…”

“…Similar designs have previously shown a significant symptom severity reduction after joint therapy ( Brunet et al, 2018 ). Surprisingly, the most recent RCT did not confirm superiority for joint therapy with propranolol over therapy plus placebo ( Roullet et al, 2021 ), but a significant proportion of patients nevertheless improved in both groups. We took this opportunity to explore dynamic brain markers of treatment response and decided to focus on re-experiencing symptoms, as one possible cause of limited treatment efficacy may rely not only on treatments themselves but also on the heterogeneity within PTSD or selective actions on certain clinical dimensions and not others ( Neria, 2021 ).…”

“…The present study intends to bring new insights to the dynamic role of the SN in PTSD and, more specifically, to circumscribe the directed influence of the AI over the rest of the brain as a function of treatment response. To do so, we analyzed fMRI data from a recent randomized controlled trial (RCT) comparing trauma memory reactivation therapy using propranolol (considered a putative reconsolidation blocker) versus the same therapy plus placebo in PTSD patients ( Roullet et al, 2021 ). Similar designs have previously shown a significant symptom severity reduction after joint therapy ( Brunet et al, 2018 ).…”

Intrusive Experiences In Post-Traumatic Stress Disorder: Treatment Response Induces Changes In The Effective Connectivity of The Anterior Insula

“…Similar designs previously showed a significant symptom severity reduction after joint therapy (Brunet et al, 2018). Surprisingly, the most recent RCT did not confirmed superiority for joint therapy with propranolol over therapy plus placebo (Roullet et al, 2021), but a significant proportion of patients was nevertheless improved in both groups. We took this opportunity to explore dynamical brain markers of treatment response and decided to focus on re-experiencing symptoms, as one possible cause of limited treatment efficacy may rely not only on treatments themselves, but also in the heterogeneity within PTSD or selective actions on clinical dimensions and not others (Neria, 2021).…”

“…The present study intends to bring new insights to the dynamic role of the SN in PTSD and, more specifically, to circumscribe the directed influence of AI over the rest of the brain as a function of treatment response. To do so, we analyzed fMRI data from a recent randomized controlled trial (RCT) comparing trauma memory reactivation therapy using propranolol (considered a putative reconsolidation blocker) versus the same therapy plus placebo in PTSD patients (Roullet et al, 2021). Similar designs previously showed a significant symptom severity reduction after joint therapy (Brunet et al, 2018).…”