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).
The Wall