Reconsolidation-based treatment for fear of public speaking: A systematic pilot study using propranolol

Abstract

Pharmacological manipulation of memory reconsolidation opens up promising new avenues for anxiety disorder treatment. However, few studies have directly investigated reconsolidation-based approaches in subclinical or clinical populations, leaving optimal means of fear memory reactivation unknown. We conducted a systematic pilot study to assess whether a reconsolidation-based treatment could tackle public speaking anxiety in a subclinical sample (N = 60). As lab studies indicate that duration of reactivation may be important for inducing reconsolidation, we investigated several speech lengths to help inform further translational efforts. Participants underwent a stress-inducing speech task composed of three minutes preparation, and from 0-9 minutes of public speaking, in one minute increments. They then received either 40mg propranolol (n = 40) or placebo (n = 20), double-blind, allocated 4:2 for each speech duration. Participants performed a second speech one week post-treatment, and were followed up with questionnaires one- and three months later. Both self-reported speech distress and questionnaire measures of public speaking anxiety showed clear reductions following treatment. However, propranolol did not reliably outperform placebo, regardless of speech duration at treatment. Physiological responses (heart rate and salivary cortisol) to the public speaking task remained stable from treatment to test. These findings highlight the challenges facing the translation of laboratory research on memory reconsolidation into clinical interventions. Lack of explicit controls for factors beyond duration, such as ‘prediction error’, could explain these null findings, but positive results in clinical interventions are needed to demonstrate that taking such factors into account can deliver the promises of reconsolidation-based therapy. This is a pre-print of an article published in the open access journal Translational Psychiatry https://doi.org/10.1038/s41398-020-0857-z

Reactivation-Dependent Amnesia for Contextual Fear Memories: Evidence for Publication Bias

“…The lack of robustness of reactivation-dependent amnesia, in combination with the strict (but vague) conditions that are required for memory destabilization and the absence of clear explanations for some of the observed null effects, cast doubt on the potential of the proposed clinical application of post-reactivation interventions for the treatment of phobias or PTSD. Indeed, studies in (sub)clinical samples have not been entirely convincing (Brunet et al, 2011;Elsey et al, 2020;Kindt and van Emmerik, 2016;Wood et al, 2015; see Beckers and Kindt, 2017 for an overview). Importantly, the mixed results obtained in clinical studies might not reflect issues with translation from basic to clinical science but may simply reflect the lack of robustness of results obtained in basic research and illustrate the lack of insight in the optimal and boundary conditions for reactivation-dependent memory interference.…”

Propranolol-induced inhibition of unconditioned stimulus-reactivated fear memory prevents the return of fear in humans

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Cardiovascular therapeutics: A new potential for anxiety treatment?

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