Single-dose propranolol tied to ‘selective erasure’ of anxiety disorders

A single 40-mg dose of oral propranolol, judiciously timed, constitutes an outside-the-box yet highly promising treatment for anxiety disorders, and perhaps for posttraumatic stress disorder as well, Marieke Soeter, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

The concept here is that the beta-blocker, when given with a brief therapist-led reactivation of a fear memory, blocks beta-adrenergic receptors in the brain so as to interfere with the specific proteins required for reconsolidation of that memory, thereby disrupting the reconsolidation process and neutralizing subsequent expression of that memory in its toxic form. In effect, timely administration of one dose of propranolol, a drug that readily crosses the blood/brain barrier, achieves pharmacologically induced amnesia regarding the learned fear, explained Dr. Soeter, a clinical psychologist at TNO, the Netherlands Organization for Scientific Research, an independent nonprofit translational research organization.Propanolol powder

“It looks like permanent fear erasure. You can never say that something is erased, but we have not been able to get it back,” she said. “Propranolol achieves selective erasure: It targets the emotional component, but knowledge is intact. They know what happened, but they aren’t scared anymore. The fear association is affected, but not the innate fear response to a threat stimulus, so it doesn’t alter reactions to potentially dangerous situations, which is important. If there is a bomb, they still know to run away from it.
This single-session therapy addressing what psychologists call fear memory reconsolidation is totally outside the box relative to contemporary psychotherapy for anxiety disorders, which typically entails gradual fear extinction learning requiring multiple treatment sessions. But contemporary psychotherapy for anxiety disorders leaves much room for improvement, given that up to 60% of patients experience relapse. That’s probably because the original fear memory remains intact and resurfaces at some point despite initial treatment success, according to Dr. Soeter.

Nearly 2 decades ago, other investigators showed in animal studies that fear memories are not necessarily permanent. Rather, they are modifiable, and even erasable, during the vulnerable period that occurs when the memories are reactivated and become labile.

Later, Dr. Soeter – then at the University of Amsterdam – and her colleagues demonstrated the same phenomenon using Pavlovian fear-conditioning techniques involving pictures and electric shocks in healthy human volunteers. They showed that a dose of propranolol given before memory reactivation blocked the fear response, while nadolol, a beta-blocker that does not cross the blood/brain barrier, did not.

However, since the fear memories they could ethically induce in the psychology laboratory are far less intense than those experienced by patients with anxiety disorders, the researchers next conducted a randomized, double-blind clinical trial in 45 individuals with arachnophobia. Fifteen received 40 mg of propranolol after spending 2 minutes in proximity to a large tarantula, 15 got placebo, and another 15 received propranolol without exposure to a tarantula. One week later, all patients who received propranolol with spider exposure were able to approach and actually pet the tarantula. Pharmacologic disruption of reconsolidation and storage of their fear memory had turned avoidance behavior into approach behavior. This benefit was maintained for at least a year after the brief treatment session (Biol Psychiatry. 2015 Dec 15;78[12]:880-6).