a neuroscientific basis for using benzos in panic disorder

Question:

J Psychiatry Neurosci. 2005 May;30(3):167-75. Selective GABAergic treatment for panic? Investigations in experimental panic induction and panic disorder. Zwanzger P, Rupprecht R. Anxiety Research Unit and Anxiety Outpatient Clinic, Department of Psychiatry, Ludwig-Maximilians-Universitat, Munich, Germany. Gamma-Aminobutyric acid (GABA) is the *most important inhibitory neurotransmitter* in the central nervous system (CNS). It exerts its rapid inhibitory action mostly through *GABA(A) receptors*, which are targets for *benzodiazepines*, barbiturates, neuroactive steroids and distinct *anticonvulsive agents*. **There is considerable evidence that dysfunction of GABA(A) receptors or dysregulation of GABA concentrations in the CNS (or both) plays an important role in the pathophysiology of panic disorder**. Currently, benzodiazepines are the only drugs directly targeting the GABA(A) receptors that are approved for the treatment of anxiety disorders. Because of their well-known anxiolytic effects, they are widely used in this setting, but *side effects limit their use in long-term treatment* (note: that’s controversial. I’ve been on Klonopin for 19 years). The question of whether drugs that selectively *increase GABA concentrations* in the CNS could improve symptoms of anxiety has been discussed. Recent investigations by our group have demonstrated that enhancement of endogenous GABA (through blockade of *GABA transaminase* by vigabatrin, or through *inhibition of GABA transporters* by tiagabine) exerts anxiolytic effects on experimentally induced panic. (Note: the above vigabatrin inhibits the breakdown of GABA by GABA transaminase, and thus increases GABA concentration. It will not be approved in the USA because a side effect is impairment of vision. The above tiagabine, trade name *Gabitril*, is now available in the USA as an anticonvulsant. It inhibits the reuptake of GABA, and thus increases GABA concentration.) Our studies in *healthy volunteers* have shown that both compounds lead to a significant reduction in panic symptoms elicited by cholecystokinin-tetrapeptide (CCK-4). Moreover, benzodiazepine-like effects on the activity of the hypothalamic-pituitary-adrenal axis have been observed in association with vigabatrin treatment. Small open studies in patients with panic disorder also showed an improvement in panic and anxiety with both compounds. This review summarizes our recent research on the effects of selective GABAergic treatment in experimentally induced panic and outlines the possible role of compounds targeting the GABA binding site of the GABA(A)-benzodiazepine receptor for the treatment of panic and anxiety. PMID: 15944741 [PubMed - indexed for MEDLINE] — The charter is available at: http://readystump.algebra.com/~asapm

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— The charter is available at: http://readystump.algebra.com/~asapm

Response:

J Psychiatry Neurosci. 2005 May;30(3):167-75. Selective GABAergic treatment for panic? Investigations in experimental panic induction and panic disorder. Zwanzger P, Rupprecht R. … Currently, benzodiazepines are the only drugs directly targeting the GABA(A) receptors that are approved for the treatment of anxiety disorders. Because of their well-known anxiolytic effects, they are widely used in this setting, but *side effects limit their use in long-term treatment* (note: that’s controversial. I’ve been on Klonopin for 19 years).

I’ll second that! I’ve been using alprazolam (Xanax) for about a decade now and have yet to experience adverse side effects nor increased dependence (works as well now as it did when I started). My dosage is purely PRN (some days I use none at all, up to 3 or rarely 4-mg during very bad days, on average about 1.5-mg per day). Best Wishes, Arthur — The charter is available at: http://readystump.algebra.com/~asapm

Response:

I’ve been taking .75 mgs per day of Xanax for about 3 weeks now, after a SEVERE panic attack (combined w/ hyperventilation) which sent me to the ER (it was my first attack I thought I was having a heart attack, despite the fact that I’m only 35 yrs old.) I love it – I can’t believe how much it has helped me! I only hope that my doctor keeps prescribing it for me, as I think it is working very well and don’t need see any need to switch. — The charter is available at: http://readystump.algebra.com/~asapm

Response:

It likely has to do with profit margins, but that’s just a guess on my part. I would be interested to know what kind of profit percentage drug companies make on, for instance, generic clonazepam, and compare it to that of name-brand Wellbutrin or Prozac. I wonder if that information is available to the general public. Deirdre

The profit margins are huge for non-generic medications sold in the USA. There are a few factors for this. 1. There is a very large initial outlay of money to bring a new medication to market. The research has to be done. Then all the trial studies to prove the medication is safe and effective so it can get FDA approval. Once on the market, the non-generic medication has a limited time that it is patent protected. This time period is where the pharmaceutical company can charge crazy prices so it can get back the initial costs and make a profit before the generics are allowed. 2. Here in the USA we pay more for the same medication than most other places in the world. We (USA) are subsidizing medications for most of the world. The pharmaceutical companies say they "donate" medications to needy nations/people around the world. The pharmaceutical companies are not really doing that. They are selling medications in those places as cost or a small loss, while they recoup it all here in the USA. Our close neighbors in Canada can get the same medication for a lot less than we have to pay here in the USA. I only see two solutions. 1. Make *all* medical research sponsored by tax dollars only. This way all the fruits of this research will be in the *public domain*. Any private company can then use that research. Since anyone can use this research the only thing companies can do is *compete*. They will have to compete on prices/services. 2. Go to a full socialized health system similar to Denmark. A friend of mine is from Denmark and according to her the health system there is much, much better. Everyone is covered. No one has to worry about whether they will eat or get their medication. Jim — The charter is available at: http://readystump.algebra.com/~asapm

Response:

- Hide quoted text — Show quoted text – why is the general opinion of most psychiatrists in favor of ssri’s over benzo’s for anxiety and panic? what is their problem with benzo’s? They usually site 3 reasons: 1) benzos can cause dependence (but so can antidepressants) 2) benzos can cause a withdrawal syndrome when stopped (so can antidepressants) 3) benzos are "addictive" (studies have shown that benzo abuse is rare in people with anxiety disorders) And another factor is that psychiatry professors who teach residents and write the psychiatric textbooks are very often paid consultants by the manufacturers of antidepressants. I am uncertain to what extent this biases them against benzos and for antidepressants. Chip

Response:

I’ve been on an SSRI, Zoloft, to prevent depression for several years, and it works. But I think the benzos are better for anxiety. thats why i keep wrestling with the thought that i would be better off on a benzo instead. i hate not knowing who to trust, we put our lives in these pdocs hands…and to think that their hands may be controlled by the strings of corporations makes me very uneasy.

You make some good points, Russ. Chip — The charter is available at: http://readystump.algebra.com/~asapm

Response:

why is the general opinion of most psychiatrists in favor of ssri’s over benzo’s for anxiety and panic? what is their problem with benzo’s?

SSRI’s are hyped up big time while benzos are (wrongly) felt to be *addictive*. They should do their homework. Philip — The charter is available at: http://readystump.algebra.com/~asapm

Response:

chip, <And another factor is that psychiatry professors who teach residents and <write the psychiatric textbooks are very often paid consultants by the <manufacturers of antidepressants. I am uncertain to what extent this biases <them against benzos and for antidepressants. thats the kind of stuff that makes my stomach turn. i cant stand the thought that money and greed overrides the compassion for suffering human beings. i could never do that…i couldnt sleep at night. i guess its because i know all to well how it feels, and i would never wish that on anyone. that is also why i dont trust these ssri’s. thats why i keep wrestling with the thought that i would be better off on a benzo instead. i hate not knowing who to trust, we put our lives in these pdocs hands…and to think that their hands may be controlled by the strings of corporations makes me very uneasy. russ — The charter is available at: http://readystump.algebra.com/~asapm

Response:

why is the general opinion of most psychiatrists in favor of ssri’s over benzo’s for anxiety and panic? what is their problem with benzo’s? — The charter is available at: http://readystump.algebra.com/~asapm

Response:

why is the general opinion of most psychiatrists in favor of ssri’s over benzo’s for anxiety and panic? what is their problem with benzo’s?

They usually site 3 reasons: 1) benzos can cause dependence (but so can antidepressants) 2) benzos can cause a withdrawal syndrome when stopped (so can antidepressants) 3) benzos are "addictive" (studies have shown that benzo abuse is rare in people with anxiety disorders) And another factor is that psychiatry professors who teach residents and write the psychiatric textbooks are very often paid consultants by the manufacturers of antidepressants. I am uncertain to what extent this biases them against benzos and for antidepressants. Chip — The charter is available at: http://readystump.algebra.com/~asapm

Response:

J Psychiatry Neurosci. 2005 May;30(3):167-75. Selective GABAergic treatment for panic? Investigations in experimental panic induction and panic disorder.

I’ve *never* heard of anybody having any success with Gabitril. Of course I haven’t read the study itself but I’m far from convinced. Philip (gimme a benzo any time) – Hide quoted text — Show quoted text – Zwanzger P, Rupprecht R. Anxiety Research Unit and Anxiety Outpatient Clinic, Department of Psychiatry, Ludwig-Maximilians-Universitat, Munich, Germany. Gamma-Aminobutyric acid (GABA) is the *most important inhibitory neurotransmitter* in the central nervous system (CNS). It exerts its rapid inhibitory action mostly through *GABA(A) receptors*, which are targets for *benzodiazepines*, barbiturates, neuroactive steroids and distinct *anticonvulsive agents*. **There is considerable evidence that dysfunction of GABA(A) receptors or dysregulation of GABA concentrations in the CNS (or both) plays an important role in the pathophysiology of panic disorder**. Currently, benzodiazepines are the only drugs directly targeting the GABA(A) receptors that are approved for the treatment of anxiety disorders. Because of their well-known anxiolytic effects, they are widely used in this setting, but *side effects limit their use in long-term treatment* (note: that’s controversial. I’ve been on Klonopin for 19 years). The question of whether drugs that selectively *increase GABA concentrations* in the CNS could improve symptoms of anxiety has been discussed. Recent investigations by our group have demonstrated that enhancement of endogenous GABA (through blockade of *GABA transaminase* by vigabatrin, or through *inhibition of GABA transporters* by tiagabine) exerts anxiolytic effects on experimentally induced panic. (Note: the above vigabatrin inhibits the breakdown of GABA by GABA transaminase, and thus increases GABA concentration. It will not be approved in the USA because a side effect is impairment of vision. The above tiagabine, trade name *Gabitril*, is now available in the USA as an anticonvulsant. It inhibits the reuptake of GABA, and thus increases GABA concentration.) Our studies in *healthy volunteers* have shown that both compounds lead to a significant reduction in panic symptoms elicited by cholecystokinin-tetrapeptide (CCK-4). Moreover, benzodiazepine-like effects on the activity of the hypothalamic-pituitary-adrenal axis have been observed in association with vigabatrin treatment. Small open studies in patients with panic disorder also showed an improvement in panic and anxiety with both compounds. This review summarizes our recent research on the effects of selective GABAergic treatment in experimentally induced panic and outlines the possible role of compounds targeting the GABA binding site of the GABA(A)-benzodiazepine receptor for the treatment of panic and anxiety. PMID: 15944741 [PubMed - indexed for MEDLINE]

– The charter is available at: http://readystump.algebra.com/~asapm

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