Talk:Alprazolam

onset of effect in panic disorder

Review article Verster et al. mentions also in this case "within the first week". The reason seems to be that during the first week e.g. in the APA algorithm the dose is titrated upward, until sufficient effect against panic attacks is achieved, even if the immediate effect of a dose is achieved within an hour. So I propose to look at this again. It IMO is currently too complicated and detailed for the lead, which should be compact. 70.137.143.254 (talk) 12:36, 1 October 2011 (UTC) 70.137.143.254 (talk) 12:36, 1 October 2011 (UTC)

I found an additional lead about the issue in literature. In panic disorder the anticipation of panic attacks creates an own contribution to the anxiety of panic disorder, so the "fear of the fear" is cause and effect of itself. The panic attack is a result of this self-reinforcing phenomenon, which is a learned behavior. If this feedback cycle is disrupted by anxiolytics, then also the learned fear of a panic attack slowly subsides, eventually the dose may then be titrated downward, as the anticipatory anxiety slowly dissipates. 70.137.143.254 (talk) 05:37, 2 October 2011 (UTC)

Bioavailibility

The BA of oral dosing is listed as 80-100%. Now, Xanax is known for having an exceptionally high BA, and certainly is over 90% in many, if not most subjects.BUT it is, to my knowledge, impossible for a drug to have 100% BA if it isn't taken parentally. SInce it can be damn near 100% even when taken orally, perhaps we should change this to 80-99%, just to be proper, or better yet, find a more exact figure.

In any case, if no one is able to provide a source of 100% when taken orally, I will change this. — Preceding unsigned comment added by 24.98.250.155 (talk) 06:40, 23 October 2011 (UTC)

C'mon, the 100% are obviously the theoretical limit. Cannot be misunderstood. Who knows if in reality it is 97%, 98%, 99%, 99.7% etc. and in whom dependent for what he had for breakfast. Less is more here, so we do not need to phantasize a guess here. We do not need to be precise with the last 10ug. It is also within the precision of measurement and more so within the precision of the dosage, which is much less. 70.137.158.132 (talk) 23:50, 24 October 2011 (UTC)

3o

October 24,2011 Dear Wikipedia editors,

Our attention was first drawn to the Wikipedia entry on Xanax when one of us, Peter Barglow MD, had a patient who had become very dependent on Xanax and who reported that he had been reassured of the drug’s safety by reading this Wikipedia entry.

We have written several times to the talk page for Wikpedia Xanax, detailing the evidence and arguments that imply that Xanax carries a substantial potential for dependence, tolerance, and “abuse,” using this word with its ordinary lay person’s meaning: doing harm to oneself and/or others by taking this drug.

In our remarks below, we will sometimes mention again evidence and argumentation that we have submitted to this talk page previously. We offer this repetition only where we feel that our remarks have not yet been addressed on this page. Please bear with us if you see material that has already been posted.

Much is controversial in the field of ental health care today. But there is a consensus of opinion, based on the experience of health care service providers as well as BZD researchers, that Xanax carries a substantial harm potential to those who use it. The experiences of doctors at a medical center in Kentucky, who have decided to stop writing prescriptions for Xanax, are typical and familiar to medical professionals who are familiar with this drug. In our previous entry to this talk page, we cited the New York Times article about this: “Abuse of Xanax Leads a Clinic to Halt Supply in the New York Times Sept 14, 2011 issue:http://www.nytimes.com/2011/09/14/us/in-louisville-a-centers-doctors-cut-off-xanax-prescriptions.html While not constituting conclusive scientific evidence, the change of policy in the Kentucky clinic illustrates the risk potential of Xanax.

Responding to the evidence-based argument we have provided regarding the substantial harm potential of Xanax, Doc James has continued to support the current sentence, near the beginning of the Wikipedia entry, to which we take exception: "The potential for abuse is low and is similar to that of other benzodiazepine, (BZD) drugs." Let’s examine what Doc James writes in his most recent reply:

1. Answering our point that the APA guidelines regarding Xanax do not rely on recent research evidence, Doc James writes: “This ref, the APA guidelines, may cite dated material, as you say. But we are citing this ref, not the references they cited, and this ref is recent, published 2009, and it has been revised 2008. If you think they made a mistake, you should discuss it with them. We cannot contribute our opinion here, but we have to take the APA guidelines as an authoritative source, which represents the majority opinion of the profession in this matter.”

The APA guidelines to which Doc James refers, however, if read carefully, do *not* support the broad Wikipedia generalization about Xanax that “The potential for abuse is low …” These guidelines concern the use of Xanax for *therapeutic* use only. They are silent about non-therapeutic uses of the drug. We pointed out in our previous communication – and this is a point that, to date, Doc James has not acknowledged or addressed in his responses -- that:

Doc James refers to an American Psychiatric Association report that was published in 1990, stating that “according to the report of the APA Task Force on Benzodiazepine Dependence, Toxicity, and Abuse, ‘There are no data to suggest that long-term *therapeutic use* of benzodiazepines by patients commonly leads to dose escalation or to recreational abuse (p. 294, our emphasis).”

But what about NON-therapeutic use, abuse and misuse? Notoriously, Xanax is not used only for therapeutic purposes. Adding the qualifier “therapeutic” to characterization of the use of Xanax -- thereby confining the evaluation of Xanax to situations where it is taken as directed by a medical practitioner -- ignores the large population for whom abuse/dependence is at issue. When abused, Xanax is often procured illegally, “on the street,” or through channels (e.g. from a relative or friend) that are not medically sanctioned. In this social context the drug is more likely to be misused than if it were used strictly according to “doctor’s orders.”

According to Louis A. Pagiaro and Ann Marie Pagliaro, Pagliaro’s Comprehensive Guide to Drugs and Substance Abuse, published by the American Pharmacists Association, 2004, “The benzodiazepines have been and continue to be, used medically for a variety of reasons. However, their medical use has often resulted in both intentional and unintentional abuse by patients and their friends and family members with whom the drug may be shared to relieve conditions similar to those for which it was prescribed.” p. 34

If we limit our evaluation of the use of just about any familiar drug – morphine, for instance – only to the instances of its “therapeutic use,” than of course the drug will score high in terms of safety. But the use of common dependency-inducing or highly addictive agents, morphine included, frequently does not adhere to the prescribed guidelines; we certainly would not say of morphine that “The potential for abuse is low.” Yes, if they were used only according to prescription instructions, agents like morphine or Xanax would be rendered “low risk.” But since that is commonly not the case, the assertion that, for Xanax, “The potential for abuse is low” is empirically unwarranted. It is noteworthy that the word "therapeutic" does not qualify the reassurances that the Wikipedia entry gives regarding Xanax. This word denotes use of a medication that follows “doctor’s orders,” as defined by frequency and dosage prescribed by an expert or doctor. So understood, “therapeutic use,” as we have argued, excludes abuse, as commonly understood by the lay public, and misuse leading to dependence and medical complications.

We observe, finally, that the APA 1990 task force report referenced by Doc James states repeatedly that the different kinds of BZDs *differ* substantially in their problematic effects. This text emphasizes (pages 19, 20, 26, 30, 35, 43, 44, 57) the greater risk factors involved in the use of short half-life, high potency benzodiazepines such as alprazolam. Note the contradiction here with the Wikipedia reassurance regarding alprazolam that the potential for abuse is “low and is similar to that of other benzodiazepine, (BZD) drugs." For example, according to the task force report:

“Schweizer et al. (1988) observed that after patients with panic disorder had been treated with alprazolam in a daily dosage range from 4 mg to 10 mg for 8 months and were then subjected to a gradual taper discontinuation, over 90% of all patients experienced marked withdrawal symptoms, usually towards the end of the taper period, and 26% of the patients were unable to stay off their benzodiazepine for longer than 1 to 3 days.” (page 26)

There is indeed, as the task force report itself makes clear, substantial evidence indicating that alprazolam use is more hazardous than is use of longer acting, lower potency benzodiazepines.

2. In response to our listing of some of the research studies and authorities attesting to the harm potential of Xanax, including the US Drug Enforcement Agency (DEA), the US Food and Drug Administration, Charles Pfizer (the manufacturer of Xanax) and the National Institute on Drug Abuse (NIDA), Doc James picks one of these sources, the DEA and point out that:

The DEA also states “Given the millions of prescriptions written for benzodiazepines (about 100 million in 1999), relatively few individuals increase their dose on their own initiative or engage in drug-seeking behavior.”

Point well taken: the DEA information contradicts itself. But what about the additional evidence provided not only by the DEA but also by the FDA, the manufacturer, and NIDA? We have submitted in our previous contribution to this talk page, ten authoritative psychopharmacological textbooks and handbooks that attest to the harm potential of Xanax. We take seriously -- and hope that Doc James and other editors of this Wikipedia entry will too -- the warnings in these books and the extensive research evidence upon which these warnings are based. The soundness of these warnings is supported as well by the other kinds of evidence that we have provided in previous contributions to this talk page.

3. In response to our discussion of the difference between the current DSM definition of “abuse” and what lay persons ordinary understand by the term, Doc James says:

"This is an article about alprazolam, as used by the majority of patients, not an anti-abuse and warning pamphlet for the relatively few who abuse it. It is also not intended to translate the article to such common language, as it is maybe understood by the abusers, if at the same time the common scientific meaning of the terms as cited from the references is lost. 'the reference says white, but the commoner should understand that they in fact mean black and the term white is just an euphemism scientists use among themselves.' Wikipedia is not investigative journalism."

Doc Jame's reply here does not address the case we have made regarding the misleading character of the sentence, "The potential for abuse is low and is similar to that of other benzodiazepine, (BZD) drugs." We have pointed out that: "Abuse” is an often used but imprecise term. Most of the readers of this Wikipedia entry will not be familiar with the technical definition of this term as defined in DSM IV-R. They will interpret “potential for abuse” to mean “potential for harm.” That is, one “abuses” a drug if one’s use does harm to oneself or to others. From a clinical perspective, kinds of harm would include misuse and dependency associated with abuse, tolerance, withdrawal, loss of function, and toxicity. These aspects of risk might not be known to the lay reader.

Assuming this common understanding of “abuse,” there is among scientists and clinicians wide agreement that the ”abuse potential” of benzodiazepines, including Xanax, is substantial, not “low” as the Wikipedia text states. Nutt et. al. published in Lancet in 2007 an article in which a group of expert scientists compared 20 agents widely considered to be addicting. (Nutt, D., King, L. A., Saulsbury, W., & Blakemore, C. (2007) “Development of a rational scale to assess the harm of drugs of potential misuse.” Lancet, 369, 1047-1053) The comparison was based on 16 criteria, 9 related to harm of the drug to the individual and 7 related to estimation of its harmful effects upon other persons. The 20 drugs were rated in regard to dependence, withdrawal reactions, reinforcement of negative behaviors and intoxication risk. Benzodiazepines (BZDs) ranked higher on dependence, with a score of 1.83, than amphetamines (1.67) and marijuana (1.51), but lower than tobacco (2.21). On the social harm criterion, BZDs ranked higher than the three other substances, with a score of 1.65, compared with amphetamines and marijuana (each scoring 1.50), and tobacco (1.42).

Doc James takes exception to the conclusions of the Nutt et al. study, but what he says does not contradict either the methodology or the scientific validity of this study’s results.

Our concern here is that most readers, being unaware of the technical definition of abuse given in DSM 4-R, will interpret “The potential for abuse is low“ as a reassurance about the safety of taking this drug, and that the consequences of this reassurance may be harmful to themselves and/or others – as may have occurred in the case of Dr. Peter Barglow’s patient mentioned above. Doc James’ remark on this matter does not address this concern.

3. Doc James writes: "Furthermore, you cite again the discontinuation symptoms and rebound symptoms as well as tolerance as evidence for abuse potential. This connection does not exist as such. The discontinuation and withdrawal symptoms and tolerance have been cited in the article as it is now. 70.137.133.93 (talk) 03:35, 4 October 2011 (UTC)"

First, for reasons given above, in an effort to convey accurate information to lay Wikipedia readers, the Xanax article should speak of “abuse potential” in the way they are most likely to understand: as the potential to do harm to themselves or to others. And the spectrum of symptoms associated with Xanax is indeed evidence for such a potential. At the very least, the article should mention that it is giving to “low abuse potential” a technical meaning, at variance with the meaning given to this phrase as it is commonly understood by lay persons who will be reading this article.

In addition, the fact that, as Doc James says, symptoms of Xanax use are “cited in the article as it is now,” doesn’t really address the problem here. Many readers who are looking for a brief appraisal of the safety of Xanax will read the first several paragraphs, which include the sentence "The potential for abuse is low, “ and, being reassured, will not read through the entire, long discussion of Xanax in order to reach the subsequent caveats.

4. Doc James goes on to say: “You do not seriously propose, to use Michael Jackson as evidence for any claims, do you?”

Michael Jackson, who was taking benzodiazepine medication under the supervision of a doctor, didn’t take the pills only in the prescribed amounts and at the prescribed times. We mentioned him only as an illustration of a problem that Doc James does not address: even if the “therapeutic use” of Xanax is low risk, that does not justify any generalizing conclusion about the use of this drug. The relevant point here, which we have submitted previously, is this:

If we limit our evaluation of the use of just about any familiar drug – morphine, for instance – only to the instances of its “therapeutic use,” than of course the drug will score high in terms of safety. But the use of common dependency-inducing or highly addictive agents, morphine included, frequently does not adhere to the prescribed guidelines; we certainly would not say of morphine that “The potential for abuse is low.” Yes, if they were used only according to prescription instructions, agents like morphine or Xanax would be rendered “low risk.” But since that is commonly not the case, the assertion that, for Xanax, “The potential for abuse is low” is empirically unwarranted. However, in questioning this Wikipedia entry claim, we are not referring here only to use of Xanax that has been obtained illegally on the street, from another user, or in some other irregular way. Even when this drug is prescribed, it is subject to abuse that, by definition, exceeds its therapeutic use. Did the celebrity Michael Jackson use the three benzodiazepines that were considered factors in his death “therapeutically”?

In this context, it seems to us that a mention of Michael Jackson, the late singer, is appropriate, not as evidence for, but as an illustration of, the point above.

5. In his response to our communications, Doc James has repeatedly asked us what, exactly, we are requesting. He writes, for example: "What one sentence do you wish to change/add?"

From the beginning, we have always specified what needs to be changed in the Wikipedia article. In our most recent communication before this one, for example, we objected to the sentence, "The potential for abuse is low and is similar to that of other benzodiazepine, (BZD) drugs." We requested that this sentence be deleted, and offered this possible alternative: "Many scientific authorities and medical experts have concluded that the use of this drug (Alprazolam) carries a substantial risk for dependence, abuse, and misuse."

6. Doc James asks about our request for a change to the Xanax entry: "What refs do you propose to support it?"

We have cited references that appear in the relevant discussions in the following sources: NIDA, the FDA and DEA; the caution on Xanax use provided by the manufacturer, Charles Pfizer; ten textbook/handbook references published in the past decade, and finally a recent report in the NY Times of Kentucky psychiatric clinicians who have banned prescription of the drug Xanax in their treatment system, because of the widespread complications of dependence that they have witnessed.

Again, we request removal of this sentence from the Wikipedia Xanax entry: "The potential for abuse is low and is similar to that of other benzodiazepine, (BZD) drugs." We suggest as a possible substitution: “Many scientific authorities and medical experts have concluded that the use of this drug carries a substantial risk for dependence, abuse, and misuse.”

If the meaning of “abuse” remains at issue here – with Doc James interpreting the term in a technical way, whereas we believe that most Wikipedia readers of this entry will read it in a more commonsensical way, then we might dispense with the term altogether and rewrite the contested Wikipedia sentence as follows:

“Many scientific authorities and medical experts have concluded that the use of Xanax/alprazolam carries a substantial potential for becoming dependent on this drug and doing harm to oneself and/or others.”

Changing the Wikipedia sentence in this way will reduce the likelihood that lay readers of the Xanax entry will be falsely reassured about the harm potential of this drug.

We of course recognize the legitimate therapeutic uses of benzodiazepines such as Xanax. But this acknowledgement ought not to lead us to misrepresent the risk factors.

Thank you for your attention to this discussion and to the issues it raises.

Peter Barglow, MD Raymond Barglow, PhD Rbarglow (talk) 16:44, 25 October 2011 (UTC)

Copied here, as it was inserted out of chronological order.

As previously stated you MUST provide reliable references to support your opinion. These need to be review articles or major textbooks within the last 10 years. Do not need a wall of text. One or two would be sufficient. Thanks Doc James (talk · contribs · email) 02:18, 25 October 2011 (UTC)

Hi there, I'm here in response to the third opinion request. Please remember that a third opinion request is only for disputes between two people. At least three people have been involved in this discussion, so a third opinion request is not really appropriate. If you have a content dispute where discussion has taken place and no common ground can be found, I would suggest that you use the dispute resolution process and make a request at the dispute resolution noticeboard.

As for the issue at hand, the key policy here is verifiability. This means that the content on Wikipedia must be verifiable by reliable sources (I suggest you look at WP:MEDRS if you haven't already). If you wish to change the description of the drug, reliable sources must be found which support the statement. Your best bet here would be secondary sources which are up-to-date. I've not been able to read through the entire discussion (or look at all the sources presented), but I suggest you look for a number of different sources which you can use to cross-reference this claim. If you have any primary sources, look to see if it can be supported with other sources. Also, ensure that your sources have no conflict of interest and are up-to-date. If you want my comments on any individual sources, just let me know. I hope I've helped in some way. ItsZippy ^{(talk • contributions)} 17:08, 25 October 2011 (UTC)

Just to add to that, some editors were expressing concern that people have been using Wikipedia for medical advice. Let me stress that this should never be done, as the accuracy of Wikipedia can never be vouched for. Doctors should always warn patients not to use Wikipedia for any kind of medical advice whatsoever. I suggest anyone concerned reads our medical disclaimer. ItsZippy ^{(talk • contributions)} 17:10, 25 October 2011 (UTC)

I'm not a chemist.

This article is a prime example of the destruction of Wikipedia. I'm sure this article reads great to someone with a PhD, but for the laypeople we've got no idea what it's saying.

So to technical than :-) --Doc James (talk · contribs · email) 16:04, 7 December 2011 (UTC)

I'd have to agree with my angry friend up here

This is what Wikipedia is like these days, please petition wikipedia to create tabs for reading levels. For example "Pupil", "Laymen", "Intermediate", "Academic". There is an article which describes this problem here:

http://meta.wikimedia.org/wiki/Reading_level — Preceding unsigned comment added by 82.39.50.82 (talk) 21:58, 6 January 2012 (UTC)