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Re: misunderstandings about benzodiazepines Alan

Posted by Elizabeth on July 30, 2001, at 16:30:28

In reply to Re: misunderstandings about benzodiazepines Elizabeth, posted by Alan on July 29, 2001, at 18:21:43

> Yes, elizabeth. Those articles would be most informative if you can provide links or relevant passages to treat anxiety or panic disorders.

OK. You can get loads of references with a cursory Medline search. Here's what a current mainstream textbook (_American Psychiatric Association Textbook of Psychopharmacology_, Schatzberg & Nemeroff eds. 1998) has to say:

"The controversy surrounding benzodiazepine administration and potential abuse or addiction in routine patient use is generally not supported by the available scientific evidence. (See Shader and Greenblatt 1993 [1] for an excellent review of this complex area.) In a large community study of long-term alprazolam users, Romach and colleagues (1992) [2] found that dosage did not escalate over prolonged use and that most patients used the benzodiazepines as prescribed. In fact, if deviations occurred, it was generally that a patient took less than the prescribed dosage. This area has been more controversial than warranted in part because of confusion over the meanings of addiction, dependence, and abuse. Recent efforts to clear up this confusion, especially differentiating abused from withdrawal symptom liability, have been helpful (Ballenger 1993 [3]; Linsen et al. 1995 [4]; N.S. Miller 1995 [5]; N.S. Miller et al. 1995 [6]).

"... Numerous groups, including some medical professionals, have perpetuated the idea that if benzodiazepines are used long term, patients become `addicted' to the benzodiazepines, implying that they will abuse them or have an extreme withdrawal syndrome when the medication is discontinued. Actually, what occurs with benzodiazepines is similar to the effects of other medications used for long-term treatment of a medical and/or psychiatric condition and can be compared to what happens when a patient's cardiovascular medication (e.g., propranolol, methyldopa) is suddenly discontinued (Garbus et al. 1979 [7]). In essence, the body goes through an adaptational process to the drug, and if medication is discontinued too abruptly, the patient can have withdrawal symptoms. The patient may also experience a transient recurrence of anxiety symptoms at levels more intense than those experienced before treatment; this is called rebound. The patient may also experience a return of symptoms that were present before treatment (relapse). However, if dosage is adjusted and gradually titrated downward, and if patients and their families are educated about what to expect during the discontinuation process, most patients can manage the transient withdrawal symptoms without much difficulty (see Ballenger et al. 1993 [8] and Shader and Greenblatt 1993 [1] for review), this area remains somewhat controversial (Ashton 1995 [9]; Lader 1995 [10] [note that these are both by British authors])."

1. Shader RI, Greenblatt DJ: Use of benzodiazepines in anxiety disorders. N Engl J Med 328:1398-1405, 1993.

2. Romach MK, Somer GR, Sobell LC, et al.: Characteristics of long-term alprazolam users in the community. J Clin Psychopharmacol 12:316-332, 1992.

3. Here, the citation is ambiguous (there is no reference listed that matches the citation). It could be one of the following:
Ballenger JC, Fyer AJ: Examining criteria for panic disorder. Hosp Community Psychiatry 44:226-228, 1993
Ballenger JC: Long-term pharmacologic treatment of panic disorder. J Clin Psychiatry 52:18-23, 1991.
Ballenger JC, Pecknold J, Rickels K, et al.: Medication discontinuation in panic disorder. J Clin Psychiatry 54 (10 suppl):15-21, 1993.

4. Linsen SM, Zitman JG, Breteler MHM: Defining benzodiazepine dependence: the confusion persists. European Psychiatry 10:306-311, 1995.

5. Miller NS: Liability and efficacy from long-term use of benzodiazepines: documentation and interpretation. Psychiatric Annals 25:166-173, 1995.

6. Miller NS, Gold MS, Stennie K: Benzodiazepines: the dissociation of addiction from pharmacological dependence/withdrawal. Psychiatric Annals 25:149-152, 1995.

7. Garbus SB, Weber MS, Priest RT, et al.: The abrupt discontinuation of antihypertensive treatment. J Clin Pharmacol 19:476-486, 1979.

8. again, ambiguous: could be
Ballenger JC, Fyer AJ: Examining criteria for panic disorder. Hosp Community Psychiatry 44:226-228, 1993, or
Ballenger JC, Pecknold J, Rickels K, et al.: Medication discontinuation in panic disorder. J Clin Psychiatry 54 (10 suppl):15-21, 1993.

9. Ashton H: Protracted withdrawal from benzodiazepines: the post-withdrawal syndrome. Psychiatric Annals 25:174-179, 1995.

10. Lader M: Clinical pharmacology of anxiolytic drugs: past, present, and future, in _GABA Receptors and Anxiety: From Neurobiology to Treatment_. Edited by Biggio G, Sanna E, Costa E. New York, Raven, 1995, pp. 135-153.

In a later chapter, the authors do note that patients with a history of drug or alcohol abuse may be at increased risk for benzodiazepine abuse, but they add that: "Such a history is not an absolute contraindication to benzodiazepine use, but these drugs should be used with particular caution in this population." A history of substance abuse may be indicative of self-medication rather than any special propensity for abusing drugs in general.

I could go on, but you get the idea.

Some references regarding the use of adinazolam and alprazolam as antidepressants:

Kennedy SH, de Groot J, Ralevski E, Reed K: A comparison of adinazolam and desipramine in the treatment of major depression. Int Clin Psychopharmacol 1991 Summer;6(2):65-76.

Feighner JP, Boyer WF, Hendrickson GG, Pambakian RA, Doroski VS: A controlled trial of adinazolam versus desipramine in geriatric depression. Int Clin Psychopharmacol 1990 Jul;5(3):227-232.

Dunner D, Myers J, Khan A, Avery D, Ishiki D, Pyke R: Adinazolam--a new antidepressant: findings of a placebo-controlled, double-blind study in outpatients with major depression. J Clin Psychopharmacol. 1987 Jun;7(3):170-172.

Ansseau M, Devoitille JM, Papart P, Vanbrabant E, Mantanus H, Timsit-Berthier M: Comparison of adinazolam, amitriptyline, and diazepam in endogenous depressive inpatients exhibiting DST nonsuppression or abnormal contingent negative variation. J Clin Psychopharmacol 1991 Jun;11(3):160-165.

Smith WT, Glaudin V: Double-blind efficacy and safety study comparing adinazolam mesylate and placebo in depressed inpatients.

Cohn JB, Pyke RE, Wilcox CS: Adinazolam mesylate and placebo in depressed outpatients: a 6-week, double-blind comparison. J Clin Psychiatry. 1988 Apr;49(4):142-147.

Amsterdam JD, Kaplan M, Potter L, Bloom L, Rickels K: Adinazolam, a new triazolobenzodiazepine, and imipramine in the treatment of major depressive disorder. Psychopharmacology (Berl). 1986;88(4):484-488.

Weissman MM, Prusoff B, Sholomskas AJ, Greenwald S: A double-blind clinical trial of alprazolam, imipramine, or placebo in the depressed elderly.
J Clin Psychopharmacol. 1992 Jun;12(3):175-182.

Hicks F, Robins E, Murphy GE: Comparison of adinazolam, amitriptyline, and placebo in the treatment of melancholic depression. Psychiatry Res. 1988 Feb;23(2):221-227.

Rickels K, Chung HR, Csanalosi IB, Hurowitz AM, London J, Wiseman K, Kaplan M, Amsterdam JD: Alprazolam, diazepam, imipramine, and placebo in outpatients with major depression. Arch Gen Psychiatry. 1987 Oct;44(10):862-866.

Eriksson B, Nagy A, Starmark JE, Thelander U: Alprazolam compared to amitriptyline in the treatment of major depression. Acta Psychiatr Scand. 1987 Jun;75(6):656-663.

...and many others.

These results seem to suggest that triazolobenzodiazepines may be less efficacious than tricyclics for severe depression, but may be helpful for milder depression or in conjunction with other antidepressants.

> These "facts" sound like the mantra for the anti-benzo lobby - mostly based in the U.K.

Yes, British doctors do seem to be much more conservative/benzophobic than doctors in other parts of the world (even the U.S.).

> Also, I don't know how many posts I've read here about "withdrawl" symptoms from ssri's - a supposedly "non-addictive" alternative to benzos.

I think this view results from an outdated and misleading idea of what constitutes "addiction." Pharmacologic dependence (i.e., the occurrence of a characteristic withdrawal syndrome upon discontinuation of the drug) isn't sufficient by itself to merit a diagnosis of addiction.





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