Talk:Alprazolam/Archive 3

Archive 1

Archive 2

Archive 3

synthesis and OR

Please do not bloat the text by maundering and drivel, which is unsupported by reference. 70.137.143.254 (talk) 07:17, 1 October 2011 (UTC)

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)

Ambiguous statement.

I'm not sure what:

Alprazolam may be used in combination with other medications for chemotherapy-induced nausea and vomiting.

is supposed to mean. Does it induce vomiting? Or used to counter it? I have a feeling I may be right in thinking that it is supposed to treat/counter it, but I know too little to be sure. — Preceding unsigned comment added by 208.52.178.66 (talk) 17:41, 19 March 2012 (UTC)

Carbon & Iodine or Chlorine atoms?

The sum-formula is a bit "dizzy". Is it ment as C₁₇H₁₃Cl N₄ or as C₁₇H₁₃C I N₄ ? The difference is a Chlorine atom or a Carbon and an Iodine atom. By the way, my organic chemistry education is old and was at an intermediate level ("pre-university"). But I remember that my teacher thaught his pupils to write f.i. alcohol (ethanol) as CH₃CH₂OH in favor of the sum-formula C₂H₅OH - or even worse C₂H₆O. However I can see that more complicated structures may need a sum-formula rather than the carbon-based version. (Most importaint thow is my first question) Boeing720 (talk) 10:23, 22 July 2012 (UTC)

Reply look at the name and the diagram in infobox. It's clearly Chlorine, not iodine. Cantaloupe2 (talk) 02:00, 7 November 2012 (UTC)

Available specific pill sizes

I removed them, because I don't think it adds to encyclopedic entry. Alprazolam is a chemical compound and the list of pill sizes is just a list of retail availability in US & Canada, much like a list of size of containers available for baking soda. Cantaloupe2 (talk) 09:18, 6 November 2012 (UTC)

Adverse effects

The adverse effects section is weird. Mania is listed as an adverse effect and a paradoxical reaction. I also don't see a reason for skin rash, respiratory depression and constipation to be listed on one line. My inclination would be to split up the latter three, and leave mania only in the paradoxical reactions section. Any issues? Archdiamond (talk) 06:34, 17 December 2012 (UTC)

Xanax worm

Why isn't any mention of the Xanax computer worm in the article? On YouTube is a video about computer worm related to this substance (e-mails, worm main file, etc.)

• Xanax Windows Worm on YouTube

178.183.164.121 (talk) 04:03, 20 February 2013 (UTC)

The article is about the drug alprazolam, so a discussion of a computer worm wouldn't be appropriate here. If the computer worm is notable, a separate page can be created for it. -- Ed (Edgar181) 13:14, 20 February 2013 (UTC)

Abuse potential of alprazolam

Dear editors of the Wikipedia Alprazolam page,

In the past, I have presented evidence regarding a statement in the Wikipedia alprazolam article that reassures readers about the low abuse potential of alprazolam. I, along my collaborator, who is also my brother, Raymond Barglow, Ph.D., regard this reassurance as mistaken and dangerous to Wikipedia readers who believe it.

A new review article, appearing in a peer-reviewed and reputable psychiatric journal, provides further evidence that the abuse potential of aprazolam is substantial for patients and non-patients alike. We wish to bring this article and its conclusions to your attention, with the aim of correcting the misleading information near the beginning of the alprazolam article, which currently reads as follows:

“The potential for abuse among those taking it [alprazolam] for medical reasons is low and is similar to that of other benzodiazepine drugs.”

We recommend that this erroneous statement be replaced by the following sentence:

“Alprazolam use may lead to substance dependence and abuse.”

We note that although cautionary statements appear later in the Wikipedia alprazolam article, the article does not state unequivocally that alprazolam use may lead to substance dependence. The article presents only dependence warnings that pertain to particular circumstances and subclasses of users of this drug. And even these warnings, which in any event occur at about the halfway point of a long article, will be missed by readers who do not read beyond the first several paragraphs.

The new review article we’re referring to here appears in the Australian New Zealand Journal of Psychiatry, and we give the full reference below to the article, published in March 2012 (electronically published in January 2012). This article affirms in no uncertain terms that, contrary to what the Wikipedia Alprazolam article asserts,

1. The potential for abuse of aprazolam is substantial, for patients as well as for non-patients.

2. There is a relatively greater risk of dependence and abuse for alprazolam, compared to use of other benzodiazepines, due to its higher potency and shorter half-life acting time.

We are responding in this message specifically to a request made by Dr. James Heilman, an editor for this Alprazolam page, who has asked us to specify a recent review of this drug that addresses the risk issues that we have been raising. Please consider this review article: S. Moylan et al., published in March 2012 (March 46(3): 212-24) in the Australian New Zealand Journal of Psychiatry, entitled: “The role of alprazolam for the treatment of panic disorder in Australia.” Although this article focuses on the use of alprazolam in Australia, its review encompasses the wider domain of discussion of, and research about, this drug, including work done in the United States.

We have posted the Moylan article on the Internet (www.barglow.com/moylan2012alprazolam.pdf), should you wish to read it in full and/or to know which studies it references. We recommend this article as a recent, well-researched, thoughtfully balanced appraisal of the benefits and abuse potential of alprazolam.

We recognize that our quotations from this article are extensive, but we believe that they are all directly relevant to the alprazolam risk potential that we’re examining. I do place in bold font a few sentences that especially deserve attention. The bold font is my emphasis, not that of the review article author.

Since the two issues listed above -- 1) Alprazolam’s potential for abuse, and 2) alprazolam’s abuse potential compared to other benzodiazepines -- are closely linked, we will not separate the Moylan article’s evidence bearing on the one issue from the evidence bearing on the other. As you can see, the article affirms both that use of this drug carries substantial potential for abuse, and that this potential is greater than the abuse potential of other benzodiazepines.

We include in the following quotations from the article a few sentences that bear on issues that are often left obscure in discussions about the safety of alprazolam, including the character of "rebound" effects and the diagnosis of "addiction." You may find this contextual information useful. We note that the appraisal of the safety of a drug like alprazolam, which has complex effects that depend on many characteristics of an individual and his/her situation, should be nuanced and cannot be "nailed down" by any single piece of evidence. Hence we offer below a number of quotations from the Moylan article; we do find all of them directly pertinent.

From the abstract of the Moylan 2012 article:

"Results: Alprazolam has shown efficacy for control of PD symptoms, particularly in short-term controlled clinical trials, but is no longer recommended as a first-line pharmacological treatment due to concerns about the risks of developing tolerance, dependence and abuse potential."

Excerpts from the body of the Moylan article:

"…'benzodiazepine use is not recommended because of the high risk of creating dependency on these drugs' (Royal Australian and New Zealand College of Psychiatrists, 2003)." (p. 213)

"Continued use of alprazolam may be influenced by prescribers’ past experiences, short-term outcome expectancy and by patient preference. Alprazolam often exhibits a much faster onset of action than the antidepressants in reducing anxiety, and learning theory suggests that the shorter the duration between the treatment and the response, the more likely behaviour will be reinforced. Clinicians' desire to relieve distress as rapidly as possible may also drive preference for use over guideline-recommended treatments." (p. 215)

"Patients may prefer the use of alprazolam to the antidepressants due to the rapid rate of onset and increased tolerability…. It is unclear why alprazolam use is trending differently to other benzodiazepines. One factor may be patient preference related to dependence…. Addiction can be defined in a number of different ways. Some definitions imply that pleasure seeking with increasing dose is required for the syndrome. However, the more preferable definition is that of the World Health Organization (WHO) in which the addicted individual experiences a 'compulsion to take the preferred substance, has great difficulty ceasing or modifying substance use and exhibits determination to obtain (the substance) by almost any means' (World Health Organization, 2011b). The definition of addiction does not absolutely require tolerance or physical dependence but always involves behaviours that accompany psychological dependence. These behaviours, however, may be subtle when the substance is readily available or prescribed. In this context patients who struggle to withdraw or dose reduce due to the severe anxiety associated with withdrawal from alprazolam can be considered addicted. The main contention to this argument is that the patient’s failure to withdraw represents the underlying efficacy of the treatment (relapse). The difficulty in disentangling the source of anxiety (underlying or drug-induced) is a factor that complicates prescription and can be considered an undesirable quality of the pharmacotherapy. It is probable that both mechanisms may be operating simultaneously. This clinical conundrum is similar to the case of the patient who has pain but is opiate dependent. A number of issues must be considered in attempting to quantify the impact of dependence and potential for harm, described in the following sections." (p. 215)

“A combination of pharmacokinetic and pharmacodynamic properties result in a drug's addictive profile, and evidence is emerging that alprazolam may have more potent effects than other benzodiazepines upon reward pathways. Benzodiazepines, like all known addictive substances, alter mesolimbic dopaminergic pathways. Changes to evoked post-synaptic currents in the ventral tegmental area in mice can be detected after even a single dose of benzodiazepine (Tan et al., 2010). It is hypothesised that this effect is mediated by GABA-A inhibition causing secondary disinhibition of dopaminergic neurons. While alprazolam has been associated with more severe withdrawal than other benzodiazepines, it has been more difficult to assess whether it is truly more addictive (Rush et al., 1993). There is some evidence that it produces more subjective euphoria, for example a study in patients addicted to opiates and receiving methadone revealed that they preferred alprazolam to other benzodiazepines (Iguchi et al., 1989). Alprazolam has been found to increase striatal dopamine concentrations in rat studies, whereas lorazepam does not show this effect (Bentue-Ferrer et al., 2001), suggesting that alprazolam may have a unique ability to interact with mesolimbic dopamine reward pathways. Behavioural reward is contingent on timing of the reward stimulus, with proximal stimuli consistently overriding distal ones. Most individuals, for example, associate the dentist with pain induction not reduction. Alprazolam shares pharmacokinetic properties that are common to other drugs of abuse: it has a rapid onset and offset of action, high binding affinity and high potency. There are additional psychological factors worthy of consideration to help explain alprazolam addiction. Addiction to a prescription medication is generally considered more socially acceptable than illicit drug use (Hernandez and Nelson, 2010). In patients who suffer anxiety, there is a pervasive risk of the symptoms of benzodiazepine withdrawal being interpreted as the symptoms of continued affliction with panic attacks (Roy-Byrne and Hommer, 1988)." (pp. 215-216)

"The difficulty of differentiating withdrawal from rebound or recurrence -- Withdrawal from benzodiazepines includes the symptoms of ‘worse anxiety, insomnia and restlessness’ (Salzman, 1991). Alprazolam, due to its short half-life, also induces inter-dose rebound symptoms (rebound anxiety) in many patients, further complicating the monitoring of underlying anxiety versus a drug-induced anxiety. This cyclical rebound anxiety can lead to further dosing of alprazolam. The negative reinforcement provided by alprazolam (in the form of relief of rebound symptoms) can be a powerful mediator of psychological dependence in the patient (Juergens, 1991). Patients taking alprazolam effectively experience at least nightly withdrawals due to its short duration of action, and the inter-dose withdrawal effects can mimic or precipitate panic. Therefore, patients can become stuck in a vicious cycle of increased alprazolam use to combat tolerance and at the same time feel more psychologically dependent to the relief provided by alprazolam. Should there be no effective alternative treatment this may be a necessary evil, but with established efficacy of the SSRIs in this patient group, the dependence potential must be regarded as a considerable adverse consequence of the use of alprazolam in the treatment of PD." (p. 216)

"The rapidity of onset of tolerance and physical dependence ... Data from the Cross-National Collaborative Panic discontinuation study and Alprazolam SR discontinuation study show that approximately 35% of patients show withdrawal symptoms after 8 weeks taking 2 to 10 mg of alprazolam per day (Pecknold, 1993). There have also been observations of a minority of patients experiencing protracted withdrawals lasting for months after discontinuation (Ashton, 1991)." (p. 216)

"Evidence indicates that alprazolam results in more severe withdrawal symptoms than other benzodiazepines. Fyer et al. (1987) found that 15 of 17 patients in a case series had recurrence or increase in panic attacks and nine had additional symptoms associated with benzodiazepine withdrawal. Thirteen of the 17 patients did not complete withdrawal within the 4 to 5 week schedule. The incidence of withdrawal reactions can be reduced by tapering more slowly, but a consistent observation is that even with slow tapering, high-potency benzodiazepines are associated with more symptomatic withdrawal (Salzman, 1991)." (p. 216)

"Of 142 patients in the long-term (mean 27.5 weeks) arm of the Cross-National Collaborative Panic discontinuation study, only 47.2% were able to discontinue alprazolam treatment. Certainly a proportion of these patients chose to stay on alprazolam due to symptom management but it is possible a proportion of the remaining 52.8% of patients suffer from adverse effects of the medication but are unable to discontinue due to withdrawal symptoms. With evidence emerging for long-term cognitive side effects and lack of comparative efficacy in comorbid depression (Birkenhäger et al., 1995) the potential harm of patients who are effectively addicted to alprazolam must be considered." (p. 216)

"Prescription as a co-administered medication (e.g. as needed ‘PRN’) -- A further possible explanation for increased prescription of alprazolam may relate to its use in short-term co-prescription with antidepressants, or prescription on an 'as needed' (PRN) basis. The APA (American Psychiatric Association, 2009) and RANZCP (Royal Australian and New Zealand College of Psychiatrists, 2003) guidelines suggest such usage may be appropriate, but caution this practice in the context of potential issues related to withdrawal and dependence. The practice of as needed dosing, which could be motivated by efforts to prevent dependence, is also not without its risks. The APA guidelines warns that such practice 'promotes fluctuating blood levels that may aggravate anxiety' (American Psychiatric Association, 2009) and cite evidence suggesting PRN benzodiazepine dosing is associated with worse outcomes in patients receiving cognitive-behavioural therapy (CBT) for PD (Westra et al., 2002). Rapid relief of distressing symptoms is a potent behavioural reward, which potentially drives repeated use towards later dependence." (pp. 216-217)

"Rebound anxiety and withdrawal symptoms -- Rebound anxiety and withdrawal symptoms are clinically significant issues with the use of alprazolam (Verster and Volkerts, 2004) and have been discussed at length previously. Rebound anxiety and inter-dose symptom return are common with discontinuation of alprazolam (Andersch et al., 1991; Fyer et al., 1987; Pecknold, 1993; Pecknold et al., 1988), and appear to occur more often than with other benzodiazepines (Wolf and Griffiths, 1991). Rebound anxiety, issues with withdrawal syndromes and physiological dependence ‘appears to be greater among patients taking benzodiazepines with short-to-intermediate elimination half-lives’ (Chouinard, 2004). Alprazolam demonstrates a short half-life, a high binding affinity to the GABA receptor and a rapid onset and offset of action, properties that are associated with greater risk of dependency and withdrawal (O’Brien, 2005)." (p. 218)

"Longer-term side effects -- Chronic alprazolam use is associated with long-term adverse effects (Verster and Volkerts, 2004) on memory (Leufkens et al., 2007; Vermeeren et al., 1995;Verster et al., 2002), driving ability (Leufkens et al., 2007; Rapoport et al., 2009; Vermeeren et al., 1995) and psychomotor performance (Leufkens et al., 2007; Vermeeren et al., 1995). The level of memory impairment produced by benzodiazepines appears to be related to a higher relative lipid solubility and affinity at benzodiazepine receptor (Chouinard, 2004). Alprazolam exhibits both high relative lipid solubility and high binding affinity." (p. 219)

"Abuse potential and non-clinical effects -- Probably as a consequence of its high potency, rapid onset and short half-life (Chouinard, 2004; Mumford et al., 1995; Wolf and Griffiths, 1991), alprazolam has become a drug of abuse (Forrester, 2006; Substance Abuse and Mental Health Services Administration, 2010).... Alprazolam is a common drug in overdose incidents leading to emergency department admissions (Buukx et al., 2010; Substance Abuse and Mental Health Services Administration, 2010). Data from the US Substance Abuse and Mental Health Services Administration (SAMHSA) showed that alprazolam is the most common benzodiazepine involved in emergency overdose situations, both in isolation and mixed with alcohol and other substances (Substance Abuse and Mental Health Services Administration, 2010). These data also suggest the incidence of alprazolam events is increasing at a faster rate than other benzodiazepines, from approximately 46,000 in 2004 to 80,000 in 2008 (73% increase) (Substance Abuse and Mental Health Services Administration, 2010). This finding may relate to the fact that alprazolam is the most utilised benzodiazepine in the US population. In an Australian study of emergency department visits, the majority of alprazolam used in overdose was obtained through doctor prescription (Buukx et al., 2010). This high use of alprazolam in overdose is noteworthy, as in such situations alprazolam has demonstrated greater toxicity than other benzodiazepines with patients in one study 2.06 times more likely to require treatment in an intensive care unit than other benzodiazepines after adjusting for age, dose, gender and co-administered drugs (Isbister et al., 2004). It should be noted, however, that in overdose alprazolam (like other benzodiazepines) may be safer than other medications utilised for PD (e.g. TCAs)." (p. 219)

"... the available comparative evidence does not suggest that alprazolam confers an advantage over other benzodiazepines in PD treatment (Moylan et al., 2011) and it may potentially have more pronounced adverse effects owing to its high potency and short half-life." (p. 219)

"Inappropriate prescription of a medication is more likely to occur where prescribers have less experience or familiarity with the appropriate use of the drug and knowledge of available alternatives. Given alprazolam has only a narrowly defined supported indication under the PBS, and limited indication in the treatment of PD in clinical practice guidelines, it is possible a lack of familiarity with treatment guidelines is contributing to inappropriate use. .... increasing prescription and utilisation are potentially associated with an increased incidence of medication misuse." (p. 220)

In summary, these extracts from the Moylan article contradict the current Wikipedia statement about alprazolam: "The potential for abuse among those taking it for medical reasons is low and is similar to that of other benzodiazepine drugs." Because this statement is erroneous, we request that it be replaced by this statement: "Alprazolam use may lead to substance dependence and abuse." This alternative is amply supported by the Moylan article, as well as by additional evidence that we have presented over the past several months.

Sincerely,

Peter Barglow, M.D., psychiatrist in collaboration with Raymond Barglow Ph.D., psychologist Berkeley, CA Pbarglow (talk) 19:43, 7 May 2012 (UTC)

Thank you for taking your time to write your concerns regarding article content and for bringing this 2012 review paper (and it's full text) to the attention of wikipedia editors. I agree that the article was not neutral especially given this most recent review on the subject matter. Hopefully the additions made sourced to this 2012 review will have resolved the neutrality issues now and our readers can get a more neutral viewpoint on alprazolam.--MrADHD | T@1k? 14:26, 27 October 2012 (UTC)

Well, that is the opinion of two investigators who base their views heavily on the biases of a third investigator (not to say that I don't have my own biases, which will become evident shortly).

The literature is strewn with studies that come to the opposite conclusions regarding the safety of alprazolam and related compounds, to list just a few:

Schweizer et al. (58) have conducted an 8-month, placebo-controlled study of continuation therapy for panic disorder with alprazolam and imipramine that found sustained efficacy for both compounds with no dose escalation, suggesting an absence of tolerance to the therapeutic effect

Preliminary evidence for the efficacy of continuation therapy of GAD comes from two studies (43, 47). In both studies the benzodiazepine therapy achieved sustained remission of anxious symptomatology with no tolerance and no dose escalation over a 6-month period.

http://www.acnp.org/G4/GN401000129/CH127.html

A total of 136 patients received clonazepam nightly for a mean 3.5 (+/- 2.4) years, with no significant difference in initial versus final mean dose: 0.77 mg (+/- 0.46) versus 1.10 mg (+/- 0.96). Similar results were obtained with chronic alprazolam treatment and with other benzodiazepine treatments. CONCLUSION: Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep resulted in sustained efficacy in most cases, with low risk of dosage tolerance, adverse effects, or abuse.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8629680&query_hl=1&itool=pubmed_docsum

Fifty-nine panic disorder patients originally randomized to treatment in a controlled trial comparing alprazolam, clonazepam, and placebo were reevaluated in a follow-up study. At a mean follow-up of 1.5 years, 78% of patients remained on medication and the mean dosage of alprazolam and clonazepam did not increase.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8376613&query_hl=1&itool=pubmed_docsum

A 15 year study: Maintenance medication was common. No benzodiazepine abuse was reported. CONCLUSION: PD has a favourable outcome in a substantial proportion of patients. However, the illness is chronic and needs treatment. The short-term treatment given in the drug trial had no influence on the long-term outcome.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14680716&query_hl=1&itool=pubmed_docsum

I think this is interesting because it basically says the physicians are quite prejudiced concerning benzo use, even when it comes to outcome. Who knows the benefits better, the physician or the patient? That’ s easy.

The participants were 93 patients over 60 years of age using a benzodiazepine for insomnia and 25 physicians comprising sleep specialists, family physicians, and family medicine residents. The main outcome measure was perception of benefit and risk scores calculated from the mean of responses (on a Likert scale of 1 to 5) to various items on the survey. RESULTS: The mean perception of benefit score was significantly higher in patients than physicians (3.85 vs. 2.84, p < 0.001, 95% CI 0.69, 1.32). The mean perception of risk score was significantly lower in patients than physicians (2.21 vs. 3.63, p < 0.001, 95% CI 1.07, 1.77). CONCLUSIONS: There is a significant discordance between older patients and their physicians regarding the perceptions of benefits and risks of using benzodiazepines for insomnia on a long term basis. The challenge is to openly discuss these perceptions in the context of the available evidence to make collaborative and informed decisions.

. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12019038&query_hl=11&itool=pubmed_docsum

The Task Force Report, although over 10 years old, is still a standard reference for benzodiazepine use. Its points—that there is undue reluctance to use minor tranquillizers, and that many people are under treated—still hold, and are borne out by the Roy-Byrne study. Other relevant literature includes a review of 2719 adult out-patient charts2 (medical and psychiatric) for evidence of benzodiazepine abuse that found no patients meeting the criteria. Another study, of long-term alprazolam users, found no dose escalation with long-term use.3 Tyrer’s 19884 paper on minor tranquillizers notes an absence of evidence that benzodiazepine dependence leads to dangerous long-term sequellae, and blames "excessive media attention" for distortion of scientific attitudes.

http://fampra.oxfordjournals.org/cgi/content/full/20/3/347

Benzodiazepines are relatively safe drugs that are probably under- rather than overprescribed. Periodic reassessment of chronic users is appropriate, although generalized anxiety disorder and panic disorder are chronic conditions for which long-term treatment may be necessary. In the more recent era of safer antidepressants, these agents may be able to supplant minor tranquillizers for the control of chronic anxiety in many patients. Long-term benzodiazepine use is appropriate for some patients.

http://fampra.oxfordjournals.org/cgi/content/full/20/3/347

Tolerance is the need to increase the dose of a drug to maintain the desired effects. Tolerance to the anxiety-relieving effects of benzodiazepines is uncommon and most individuals do not increase their benzodiazepine dose

http://www.daap.ca/factsonbenzodiazepines.html

http://www.psychservices.psychiatryonline.org/cgi/content/full/54/7/1006

Dehughes (talk) 16:56, 24 March 2013 (UTC)

Illegal

Instead of -- or in addition to -- the opaque, though accurate, sentence about this drug being a controlled substance, can't the article say that in the United States, it is illegal to own/use/sell/? this drug except by doctors/pharmacists/... ? Until a couple days ago, I had never heard of this drug and simply came here to find out if it is illegal to use it. Why can't I get a quick and simple answer to this question? (Cf. discussions on difficulties of Wiki articles.) 202.179.19.8 (talk) 09:08, 13 February 2013 (UTC)

No, alprazolam is not illegal to use, sell, or prescribe. A "controlled substance" means none of the preceding; it simply means that the drug has some characteristics that make it wise to insure that it prescribed and used as it is intended; in this case, for anxiety and depressive disorders, among others.

Dehughes (talk) 19:30, 26 March 2013 (UTC)

Street names for Alprazolam

I've seen User:JoshG1977 attempt to add street names for alprazolam four times in this article and be reverted each time (new contributor).

Would it be acceptable to possibly include some of these slang terms under Alprazolam#Recreational use (not within the lead)—I hate to see someone get banned if they genuinely are trying to contribute, and don't remember any specific prohibitions on slang terms in the Manual of Style. Thoughts?

I realize extra caution should be exercised, since this is a "Good Article", with a lot of viewers. meteor_sandwich_yum (talk) 22:31, 11 February 2014 (UTC)

Yes I feel it to be important to add street names so more people would know wwhat it's is. Bc think if parents heard there child speaking of footballs they would think our kid is talking sports and they could overlook child doing a very addicted drug. I thought being banned was wrong bc I tried to help. I'm a huge fan of Wikipedia. It's my only ssource from Internet I find correct most of time. — Preceding unsigned comment added by JoshG1977 (talk • contribs) 04:55, 12 February 2014 (UTC)

Are there citable WP:RS for them? DMacks (talk) 05:03, 12 February 2014 (UTC)

I found some. Are they satisfactory? I tried to stay away from Ask.com or Yahoo answers and such.

• http://prescription-drug.addictionblog.org/top-10-street-names-for-valium-diazepam/
• http://www.axisresidentialtreatment.com/valium-addiction/
• http://www.substanceabuseusa.org/addictions/valium.html/

meteor_sandwich_yum (talk) 22:44, 12 February 2014 (UTC)

I'm assuming that was rhetorical, DMacks.

• JoshG1977 gave "Wagon wheels" [1], "Joshies" (local to Arizona) [2], [3], and "bars, footballs, calm pill[s], purple footballs, blue wafers, zanies, Joshies" [4].
• Unfortunately, slang local to Arizona will have to go: Wikipedia is seen by so many people, we really can add only the most common ones. I'm thinking this prescription drug addiction blog is a good starting point, as it gives the top ten and seems reliable enough. I'm going to then cross-reference this with other sources to get a wider viewpoint. By the way, I'm going to leave out "8. Howards (for Howard Hughes, a notorious Valium user)" because that can be considered libel.

I'm going to start editing this so the Evil In-group (a.k.a. Cabal) (joking!) reverts me rather than you, Josh. Wikipedia: Bold, revert, discuss should take it from there. meteor_sandwich_yum (talk) 20:08, 14 February 2014 (UTC)

Facepalm. Wrong drug entirely! meteor_sandwich_yum (talk) 20:16, 14 February 2014 (UTC)

Rewording

Paragraph 2 of the introduction reads like a commercial.— Preceding unsigned comment added by 75.154.84.151 (talk) 04:19, 5 May 2013 (UTC)

I have made a couple of small changes. Is this okay?--MrADHD | T@1k? 08:22, 5 May 2013 (UTC)

"Other uses include chemotherapy induced nausea, together with other treatments."

I don't think people use Xanax to do chemotherapy specifically with induced nausea. I think maybe anyone who isn't at least a little autistic should avoid working on wiki info. — Preceding unsigned comment added by 174.55.202.76 (talk) 05:56, 17 December 2018 (UTC)