Posted by Rick on November 9, 2001, at 3:36:51
In reply to Re: Vivid Evidence of Provigil Anti-Anxiety Effects » Rick, posted by Mitch on November 8, 2001, at 9:39:23
Mitch --
I can understand your concern with taking anything you believe might have the potential to increase panic attacks. If I were you, I’d really want to know if others with PD – not just any anxiety disorder -- had used Provigil (with a known anxiolytic), and how they fared. (Although I have noticed that, with a few notable exceptions, whatever works for panic seems to be good for social phobia, and vice versa.)
Let me start by responding to your questions about the GABA-inhibition issue first, then I'll get to the rest.
At least acording to the manufacturer, Provigil’s action is primarily (though not exlusively) in the *anterior* hypothalamus and the caudate, two areas which are not thought to be core to panic. (Most of what I’ve read implicates the limbic system and the amygdala as the key regions in panic.) This is in distiction to amphetamine, where the increases in glucose utilization are widespread in the brain. (BTW, the *lower* portion of the caudate is implicated in OCD – maybe that’s why I’m seeing NO reuction in my OCD tendencies??) The anterior hypothalamus is indeed important in regulation of wakefulness and circadian rhythms, thus acounting for much of Provigil’s efficacy. BTW, the study looking for GABA effects from Provigil in these regions found none, concluding that the wakefulness enhancement was due to glutamate enhancement.
The remaining rodent-brain studies reached conflicting conclusions about the ability of modafinil to inhibit GABA in areas of the brain where the med is less concentrated. While results by study/brain region vary from direct GABA inhibition to (theorized) indirect inhibition to no inhibition, I notice that even the “small” doses – the ones that were less likely to show a GABA effect -- were the equivalent of 30 to 100 times the Provigil dosage I take per kg of body weight. And in the one abstract where the GABA reduction was quantified, it was about 15% -- at 300 times my dosage per kg -- in select portions of the basal ganglia.
Maybe I’m missing something, but with a possible 15% GABA reduction, at a ridiculously high dosage, in a brain region that isn’t core to anxiety, I tend not to be too concerned about any anti-GABA effects causing anxiety or diminishing the effectiveness of my Klonopin or Serzone.
Perhaps taking even a small risk lightly is cavalier when the idea is to avoid doing anything that might trigger severe panic, but for me – and a big YMMV here – the key finding is that Provigil greatly enhances my Klonopin/Serzone social phobia treatment. That’s why I subtitled my original post “Pharmacology/Shmarmacology” and “Hey, Whatever Works.”
Now, as far as your other (related) questions...I‘ve had one full-blown panic attack, and a few instances where I was teetering precariously on the edge but started regaining control just in time, e.g., just before bolting from a room full of people waiting for me to present. All of the episodes were situational. One occurred when I was on solo selegiline, one was when I was on solo Nardil (post poop-out), and two were pre-meds (and led to my seeking treatment). There was another time when I went to the emergency room thinking I might be having a heart attack due to persistent chest pains, but I was calm and knew there was probably another cause. I was just being cautious, don’t think it was panic. In retrospect, I think it was gallstone pain lasting a lot longer than usual. In fact, including this episode here is probably superfluous, but I'll leave it anyway.
I've heard of the coffee test, too but I never heard that it was said to *help* social phobics --just that it doesn't cause anxiety. But caffeine DOES negatively affect my treatment enough that I avoid it, although not scrupulously. I drink plenty of caffeinated coffee on the weekend. (BTW, that's when I allow myself free rein to EAT whatever I want, too. I think weight loss has definitely contributed to my treatment.) In any event, I'm sure the cofffee test for panic refers to a MUCH greater increase in anxiety than I experience.
Rick>It sounds like it might be effective for my attentional troubles, however I wonder why you are finding it anxiolytic given its putative mechanisms of action? The inhibition of GABA and boost in glutamate makes me a little concerned that it could cause a much lowered seizure threshold and possibly trigger panic. Did you have situational full-blown panic attacks with your SP? If so, and the Provigil seems to *help* that makes me wonder about the difference between "free-floating" versus "situational" panic. I think I read something here weeks ago that talked about a "coffee" test for panic. The poster mentioned that coffee is rarely tolerated by people with "free-floating" panic, while it seems to reduce anxiety/panic in SP folks.
poster:Rick
thread:83383
URL: http://www.dr-bob.org/babble/20011104/msgs/83636.html