phobias and propranolol

there was a recent op-ed in the NY Times by the psychiatrist Richard Friedman on phobias and medical therapy (see http://www.nytimes.com/2016/01/24/opinion/sunday/a-drug-to-cure-fear.html?emc=edit_th_20160124&nl=todaysheadlines&nlid=67866768&_r=0 ). his points:

--29% of Americans have some anxiety at some point in their lives

--he cites a pretty remarkable study on using propranolol to block this anxiety, perhaps from blocking norepinephrine action (see article and review below)

--he also raises the interesting contrary concern: stimulants (eg ritalin) can cause release of norepinephrine and could theoretically enhance fear/anxiety, or even PTSD in those exposed to trauma. he notes that soldiers exposed to stimulants did in fact have more PTSD in Iraq and Afghanistan, controlling for attention deficit disorder.

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a small study was done looking at the effects of the b-blocker propranolol in inhibiting memory reconsolidation and decreasing the phobia (see phobia and propranalol biopsych2015 in dropbox, or Biological Psychiatry 2015; 78:880). the stimulus for the study was that fear memories are now considered not to be indelible memories, but ones which on reexposure to the object of fear, leads to neural protein synthesis and reconsolidation of that memory.  animal studies suggest that b-blockers can disrupt this process of reconsolidation and decrease anxiety. based on this model, a small study was done of humans with arachnophobia. details:

--15 people with arachnophobia (fear of spiders) received a single dose of propranolol, 40mg, vs 15 who received placebo, after a 2-minute exposure to a tarantula.  an additional group received propranolol without the arachnid exposure

--after the above treatment (propranolol or placebo), the patients stood in front of an open-caged tarantula at a distance of 60cm, then were asked to approach and attempt to touch the spider with their bare fingertips. patients were tested at 16 days post-exposure, 3 months, and again at 1 year

--results:

    ​--the effect of the propranolol was striking and longstanding: patients were able to handle the tarantula after propranolol but not placebo, from the 16-day test to that at 1 year, without any falloff over time. in fact, all of the participants in the propranolol group were able to touch the tarantula 16 days later, 3 months later and 1 year later.  in the other groups (both those on placebo and those on propranolol but not previously exposed to the tarantula), patients "barely touched the container" and demonstrated fears on approaching the container throughout the follow-up period. so, it was not just giving propranolol alone: taking propranolol without the tarantula exposure had no protective effect

    --in the group exposed to the tarantula, there was no effect of the propranolol in the patients' self-declared fear of spiders at the 16 day post-exposure test (though, as noted, they were able to physically handle the spider at that time). but at 3 months there was less reported fear of spiders, and this persisted for the 1-year test

so, a few points:

--pretty remarkable that a single dose of propranolol can block the phobia for at least one year (though there were small numbers of patients in this study, propranolol certainly seems worth trying, it being a known and pretty innocuous med). data from cognitive-behavioral therapy and extinction therapy (progressively increasing exposure to the feared object) show effectiveness, though that lasts only a brief time (personal testimony: i have some significant fear of heights. when i need to work on the roof of my house, it is really anxiety-provoking the first or second time up the ladder. but after a few times, i am fine going up and down, without concern -- except that i am very careful. but then several  months later, i am back to square one....)

--and it is pretty interesting that the physiologic effect of propranolol is initially distinct from the cognitive effect, in that patients still stated they were still afraid of spiders at the day-16 test.

--there are also some preliminary evidence that b-blockers decrease physiological responses to re-experiencing trauma in people with PTSD (it might be really interesting to try propranolol just after a person with PTSD has an experience which brings back memories of their trauma...). but, as a conceptual aside, ​i have seen several articles on the use of prazosin for PTSD (eg, see AnnPharmacother 2007; 41: 1013)​, especially for decreasing the associated nightmares, and i have treated several patients with great, rather unexpected success.  the concept is that sleep disorders are common with PTSD (70%), and that prazosin inhibits norepinephrine and perhaps thereby decreases the arousal in response to a stressor. in my experience, even very low dose prazosin has had dramatic results (eg 1-3 mg at night), though a recent article (Ther Adv Psychopharmacol 2014; 4: 43) notes that often higher doses are needed for full responses. these researchers also present 2 cases of patients of patients with psych comorbidities, one with PTSD and underlying major depressive disorder, but with a lot of daytime symptoms as well (hyperarousal, flashbacks, and re-experiencing the trauma) who responded pretty dramatically to prazosin 15mg in the am, 10mg at noon, and 20mg at night, and this high dose was very well-tolerated. the second patient with long-standing treatment-resistant major depressive disorder, PTSD and panic disorder and having failed a litany of meds, had lots of flashbacks, hypervigilance, reliving the experience, avoidance, nightmares, insomnia and concentration difficulties. she was titrated up to a dose of prazosin 15mg in am, 5mg at noon, and 10mg at night, and was also put on clomipramine for the depression, with a phenomenal response (PHQ-9 of 0 and asymptomatic PTSD).

--so, as more studies unfold, the brain seems to be increasingly plastic/reprogrammable (ie, it is not set for life at age 2, or 20, or ....)