Talk:Lorazepam

Flunitrazepam Inclusion/Facilitation of Criminal Activity

Under society and culture > recreational use, a paragraph is dedicated to discussing flunitrazepam's potential usage in facilitating criminal activity, especially date rape and robbery; however, flunitrazepam and the issue in general is not mentioned on any other pages dedicated to specific benzodiazepines, and there's little evidence that most common benzodiazpeines see appreciable usage in the above mentioned criminal activity, likely due to the fact that unlike flunitrazepam, other benzodiazepines generally possesses relatively minor polar solubility and thus will not dissolve readily in most common beverages, making it far more difficult to administer the drug without a subject's knowledge.

In essence I feel the section is out of place and potentially confusing/misleading, but as someone not especially familiar with the dos and don'ts of wiki editing I don't feel comfortable just deleting it based purely on personal judgement, so I figured I'd at least bring it up here. 100.19.116.119 (talk) 17:57, 17 August 2019 (UTC)

Respiratory Depression

DocJames and I seem to be having multiple disputes on various pages. I am a physician-pharmacologist who has been teaching at one of the largest research medical schools in the US for 26 years, but I don't get to editing Wikipedia often. When I do, it's to correct something just too absurd or troublesome to let go. The issue here is whether any benzodiazepine causes respiratory depression, and DocJames cites a Cochrane review focusing on a different subject in support of this relationship. This is not support because neither respiratory depression nor benzodiazepines was the focus of the review, and it is - indeed just a review of published work, not data in its own right. Actual primary data says something quite different, for example: G. E. Carraro, E. W. Russi, S. Buechi, and K. E. Bloch. Does oral alprazolam affect ventilation? A randomised, double-blind, placebo-controlled trial. Journal of Psychopharmacology 23 (3):322-327, 2009. Papers like this, done with modern methods, strongly deny a respiratory depressant effect of benzos, and can explain why earlier investigations were misinterpreted.

This isn't an idle discussion. The opioid overdose epidemic and its "association" with benzos is a very big deal in the US right now, with an immense amount of litigation surrounding it. In the midst of flaring accusations and repetitively-quoted misleading concepts, it is more important than ever to read the PRIMARY literature (not merely side issues mentioned in review literature). Verytas (talk) 17:04, 20 October 2019 (UTC)

The problem is reading primary research in isolation, which is why we prefer review articles, per WP:MEDRS. But anyway, your above study had the following methodology: “20 healthy men ingested 1 mg of alprazolam“. Your source then goes on to emphasise (“Oral alprazolam in a mildly sedative dose has no clinically relevant effect on ventilation in healthy, awake men.”) that the dose used is mild (I wouldn’t call 1 mg mild but the point is much higher doses are used in certain medical settings). Twenty is a very small number and since many, perhaps most, people sedated by benzodiazepines are far from “healthy” and also in medical settings, especially surgical and intensive care very high doses of benzodiazepines are more often used it means this source proves little. So really, your source is narrow and weak evidence. Your arguments really appear to be based on WP:SYN and I suggest you find reliable secondary sources, the more recently published the better, to support your position.--Literaturegeek | T@1k? 20:00, 20 October 2019 (UTC)

Yes, reading literature in isolation has pitfalls, however, I offered that as only one example of far better methodology that prior efforts. I have personally and professionally reviewed the entire world literature on this specific subject without a personal agenda or financial COI, only a high-level mandate to present the best evidence-based medical/scientific information to our students, residents, and faculty. The literature is deficient in definitive well-conducted studies, but the best evidence that is available does not support the idea that benzos cause respiratory depression. The prevailing view among those of us professionally considering the question of benzos + {opioids or alcohol} and death by respiratory depression is that either (a) benzos are implicated solely because they tend to be abused by people who are also abusing opioids or alcohol, or (b) they reduce the anxiety someone may have that would otherwise prevent them from ingesting excessive opioids or alcohol.

As for your preference for "review articles", that has far greater pitfalls than reading primary literature. The Cochrane review being bandied about has barely a handful of sentences in a 156-page document that was focused on something else entirely, and the authors actually made no attempt to review the literature on respiratory depression. Regardless of your (admittedly valid) criticisms of the Carraro study, it was a randomised, double-blind, placebo-controlled trial, well written, published prominently, peer-reviewed, and it thoughtfully considered the world literature to date in its discussion. That is vastly better evidence to those of us who are actively prescribing benzos and opioids for people, and teaching others about it, than a handful of remarks in a 156 Cochrane review about another issue entirely.Verytas (talk) 22:07, 20 October 2019 (UTC)

It is not my preference but the consensus of the Wikipedia community to use secondary sources, per WP:MEDRS and WP:V. You literally would need to convert the thinking of 98% of the community to your line of thinking on primary sources for building an encyclopedia and then have the relevant policies and guidelines overhauled. If you reviewed all of the ‘entire world literature’ on the subject matter at hand then you will most likely have published a review article somewhere, surely. You could then cite that here in the article with consensus of other editors of course. I can’t imagine you took on such an enormous research effort for the fun of it. Do you know of a better review article or meta-analysis than the Cochrane source? Benzos are indeed relatively safe in overdose alone for healthy adults, but the literature does find that a synergistic effect occurs in combination with opioids or alcohol.--Literaturegeek | T@1k? 23:18, 20 October 2019 (UTC)

This ref is clear https://www.drugs.com/monograph/lorazepam.html that it is associated with respiratory depression especially when used together with opioids.

But it also occurs when given alone in enough quantities or when given to someone with ETOH on board. Doc James (talk · contribs · email) 02:57, 21 October 2019 (UTC)

No, literaturegeek, I am not opposed to secondary sources, but your secondary source is not appropriate to the question in this case.

Also, I most certainly did not do my review for the fun of it: https://glossipvgross.files.wordpress.com/2015/02/14-7955-ac_sixteen-professors-supporting-neither-party.pdf I was not among the amici curiae for this brief, merely consulted to review and verify facts prior to filing, but I certainly concur with the opinion. As for synergy, there is simply no evidence for it, no matter how many times a poorly written secondary source may suggest it.

All this so sorely reminds me about why I have not become more involved with editing Wikipedia, it's such an utter waste of time when someone's interpretation of a largely irrelevant review overrides genuine expertise with the primary literature. Verytas (talk) 06:16, 21 October 2019 (UTC)

Well the secondary source match my professional experience of 20 years. I have seen "parenteral therapy for the management of status epilepticus" result in "hypotension, somnolence, respiratory failure"[1]

Doc James (talk · contribs · email) 12:32, 21 October 2019 (UTC)

With respect to the primary source you have provided. Sure I agree "In ... 20 healthy men ... 1 mg of alprazolam" by mouth will not likely affect respiratory function... That does NOT show that benzos never cause respiratory depression or even that they do not commonly do so.

Finding primary sources that support concern[2][3][4] is easy. Doc James (talk · contribs · email) 12:36, 21 October 2019 (UTC)

Doc James - In my professional experience, I have seen hypotension, somnolence, respiratory failure in persons after prolonged seizures before any benzo therapy. Your experience may suffer from a logical fallacy: post hoc ergo propter hoc.

My offerings: a well-written, prominently published, randomised, double-blind, placebo-controlled trial, and a US Supreme Court brief filed by 16 exceedingly well qualified and rigorously vetted pharmacologists that was extensively fact checked by many other exceptionally well-qualified persons before filing.

Your offerings: (1) an uncontrolled very small series of case reports written 17 yrs ago, (2) a small uncontrolled study of a respiratory volume monitor in which the authors had obvious conflicts of interest to develop and sell their device, and (3) a retrospective database study in which the only evidence that persons had taken benzos was that at one time they had filled a prescription for them somewhere in Taiwan.

It seems that the person who wins these "edit wars" is the person with the most time on their hands, not the person with the most scientific evidence or expertise. You win! Verytas (talk) 15:23, 21 October 2019 (UTC)

Verytas I was not suggesting that we use any of the primary sources in Wikipedia (neither the ones you provided nor the ones I provided). I was just showing how easy ones that support the opposite conclusion are to pull up. We should be using high quality secondary sources (which we do in this article and which supports the content in this article).

The American Society of Health-System Pharmacists has a review of the topic of lorazepam and discusses the concerns around respiratory depression. Why we would go looking at legal documents I am not sure.

If you refuse to follow Wikipedia's guidelines so be it. Neither your nor my claims of expertise advance the discussion. Best Doc James (talk · contribs · email) 01:56, 22 October 2019 (UTC)

Agreed. Flyer22 Reborn (talk) 03:28, 22 October 2019 (UTC)

Verytas, you may be correct and you may be incorrect but please try to understand that Wikipedia is not about an editor’s version of the WP:TRUTH, it is about what reliable sources say, per WP:MEDRS. Drugs.com is a reliable source and disagrees with you. Perhaps one day reliable secondary sources will agree with your viewpoint.--Literaturegeek | T@1k? 20:29, 22 October 2019 (UTC)