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Re: Benzodiazepine Tolerance » PaulB

Posted by Elizabeth on July 5, 2001, at 23:53:35

In reply to Re: Benzodiazepine Tolerance, posted by PaulB on July 1, 2001, at 20:30:38

> I think there are elements of tolerance down in the liver and the the CNS. This was mentioned in my former post but to continue this thread I think Elizabeth and Rmshed's theories on the decreasing effectiveness of the benzodiazepines are correct.

I'm afraid I can't take credit for the "theory" that I cited: it's well established that patients with panic disorder who are taking benzodiazepines do not become tolerant to them, as a rule -- by any mechanism.

Some anticonvulsant drugs (such as Tegretol) do induce their own metabolism with chronic use. Benzos don't do this, though.

rmshed: I'm not a doctor; I'm a student (see reference to textbooks). "Xanax.com" takes you to the web site of the pharmaceutical company that makes Xanax. http://www.lexington-on-line.com/naf_xanax.html has some of Dr. Cox's comments about Xanax. He never says that tolerance *is* caused by increased production of liver enzymes; he just speculates that it *could* be. In any case, his claim that Xanax causes tolerance in the treatment of panic disorder is inconsistent with any available data. (Patients do commonly grow tolerant to sedation and some other effects of benzodiazepines, though.)

See, e.g.:

J Clin Psychopharmacol 1998 Dec;18(6 Suppl 2):12S-18S. Panic disorder: long-term pharmacotherapy and discontinuation. Rickels K, Schweizer E.

Neuropsychopharmacology 1995 Apr;12(2):147-57. Benzodiazepine sensitivity in panic disorder: effects of chronic alprazolam treatment. Cowley DS, Roy-Byrne PP, Radant A, Ritchie JC, Greenblatt DJ, Nemeroff CB, Hommer DW.

Arch Gen Psychiatry 1993 Jan;50(1):51-60. Maintenance drug treatment of panic disorder. I. Results of a prospective, placebo-controlled comparison of alprazolam and imipramine. Schweizer E, Rickels K, Weiss S, Zavodnick S.

Int Clin Psychopharmacol 1993 Summer;8(2):115-8. Three-year follow-up of patients with panic disorder after short-term treatment with alprazolam and imipramine. Lepola UM, Rimon RH, Riekkinen PJ.

J Psychiatr Res 1993;27 Suppl 1:127-42. Maintenance drug therapy of panic disorder. Curtis GC, Massana J, Udina C, Ayuso JL, Cassano GB, Perugi G.

J Clin Psychopharmacol 1992 Oct;12(5):352-4. Discontinuation of alprazolam after long-term treatment of panic-related disorders. DuPont RL, Swinson RP, Ballenger JC, Burrows GD, Noyes R, Rubin RT, Rifkin A, Pecknold JC.

Arch Gen Psychiatry 1989 Nov;46(11):993-9. Clinical and medication outcome after short-term alprazolam and behavioral group treatment in panic disorder. 2.5 year naturalistic follow-up study. Nagy LM, Krystal JH, Woods SW, Charney DS.

Acta Psychiatr Scand Suppl 1987;335:39-46. Pharmacology of the benzodiazepines; with special emphasis on alprazolam. Soderpalm B.

-elizabeth


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