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Benzodiazepine

Nominator(s): Literaturegeek | T@1k? 08:31, 26 May 2009 (UTC)
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I am nominating this for featured article because I believe that the article has finally reached the criteria for featured article. It is indepth and comprehensive, makes extensive use of high quality recent sources, written clearly and consisely. I also believe that the article has the right balance where both professional and layman can derive a great deal of knowledge and understanding from the article subject. Of course there may be some suggestions made before it is promoted to featured article and I am open to constructive criticism or suggestions for improvements but I do believe the article is ready for featured article nomination for review and hopefully promotion.Literaturegeek | T@1k? 08:31, 26 May 2009 (UTC)

Restart, old nom; images and reliability of sources checked. SandyGeorgia (Talk) 19:19, 6 June 2009 (UTC)
  • Oppose. The sourcing is not to a professional standard: too many citations per fact; too many old papers cited; non-relevant-focus papers cited; inconsistency between sources used for the lead and the body; primary research papers cited without good reason; sources of narrow scope used where wider scope required. The article is apparently comprehensive (I'm no expert) but not discriminatory enough in the facts it chooses to present. The prose isn't consistently at FA standard and needs a copy edit (but don't advise one at this stage due to other problems). Two prose examples: there are a number of single-sentence paragraphs and paragraphs beginning with "They". The "Mechanism of action" section is utterly impenetrable to anyone without a pharmacy degree, which isn't acceptable. We must attempt to explain to the general reader how benzos work in the brain and achieve the effects they do. Why do they make you less anxious? Why do they make you sleepy? Why do they relax muscles? Why do they stop seizures?
Since sources are the foundation upon which an article is built, I don't believe these problems can be fixed quickly. The article shows some evidence of having random fact laid upon fact rather than being planned, executed and refined. The editors need to go through each section, selecting a small set of high quality and focussed sources, and build the text from what those sources say and the weight the sources afford to the facts. As an example of this practice, the seizure section was reduced from thirteen sources to three. I don't suggest this FAC be withdrawn despite my opinion that it can't be rescued in time: I hope we can get reviews by editors with expertise in English and in Medicine. Here are some (but by no means exhaustive) examples of specific problems found:
  1. The first three sentences of the third paragraph in the lead are cited to three separate papers. But the text is standard stuff that surely could be cited to one review? All threeTwo of those are written by Lader and one paper is ten years old.
  2. The next sentence on long term use cites three sources, two of which are old (20 and 18 years) and are focussed on withdrawal rather than long term use.
  3. The two sentences on pregnancy in the lead are sourced completely differently to those in the body text. The lead uses sources that are 11 and 15 years old. UPDATE: Those two sources have been appended to the citations in the pregnancy body section. But couldn't the existing ref in the body section (PMID 18378767) have done for the lead? It is up-to-date, unlike the lead sources. Colin° 12:36, 16 June 2009 (UTC)
  4. The lead text on the elderly and on drug overdose is cited to different sources than the body text.
  5. The statement on the general properties of benzodiazepam is cited to a primary research paper on genetically modified mice.
  6. The statement in "Therapeutic uses" on the various administration routes is sourced to a primary research paper from 1978 on five newborn infants with convulsions.
  7. Source PMID 7388368 is just the sort of paper we should be citing, except it is 30 years old. Surely there is a more up-to-date version?
  8. The lead statement on their properties and uses in veterinary practice is sourced to two papers: A review from 1975 on restraint methods in swine (which mentions diazepam for minor procedures) and a Bulgarian-language research paper from 1984 on the effects of powdered diazepam on various animals. Surely a vet textbook could be used, and be more clinically relevant and up-to-date. BTW: there doesn't seem to be any justification for citing non-English sources for this article.
  9. The statement "Midazolam can also be used along with other drugs in the sedation and capture of wild animals." is sourced to a primary research paper that captured nine aardvarks with ketamine combined with one of five other test drugs, one of which was midazolam.
  10. The (vet) statment "They are used before surgery as premedication for muscular relaxation" is sourced to a 20 year old primary research paper on five dogs undergoing anaesthesia. This doesn't tell us about modern vet practice. Indeed, none of the sources in the vet section could be used to document how benzos are currently used in vet practice.
  11. The statement "Benzodiazepines are also used to treat the acute panic caused by hallucinogen intoxication" is sourced to a 20-year old paper on hallucinogenic intoxication, the abstract of which says "Panic reactions may require treatment with a benzodiazepine or haloperidol." Benzos have well-known anti-anxiety properties so of course they will be used for severe panic attacks. Is this really notable, or something random a PubMed search found?
  12. The drug related crime section contains a long paragraph sourced to a single primary research study on Australian police detainees. My gut feeling is that the some of the results here may be particular to Australia during the period studied, and give different results for other countries or different demographics. Much reduced.
  13. The statement "Eclampsia also responds to them but benzodiazepines are not as effective as intravenous magnesium." is included in the "Other indications" section, but is sourced to a review of diazepam (only, so not "them") vs magnesium. The use of diazepam here is no different to its use in treating any prolonged seizure, so this isn't an "other indications". In fact, much of the "other indications" deals with anxiety situations, and we have an axiety section. And where's the muscle-relaxant indications (only tetanus and stiff person syndrome are mentioned, but "muscle spasm of varied aetiology" are an indication for diazepam)?
  14. There are far too many cases where three, four and even five citations are strung together, sometimes just to source a single sentence. I'm not sure what the cause of this is, but it isn't necessary for a subject like this. We are dealing with an mature class of drugs for which there is an abundance of high quality literature. Occasionally, a sentence or paragraph may require multiple sources when combining distinct facts, but that doesn't seem to be the case here. I don't know whether the editors are trying to strengthen an argument by citing multiple sources but that isn't necessary on WP. The other possibility, and more worrying, is that multiple sources are being combined to produce a statement that may transgress WP:OR. I'm particularly concerned about the various places side-effects/symptoms are mentioned. It is not the job of Wikipedians to pool the side effects (or withdrawal symptoms) of the various benzos and come up with a list of notable ones.
(BTW: Please can you respond below my signature rather than within the above text, to avoid breaking it up. Thanks.) Colin° 21:23, 6 June 2009 (UTC)
Thank you for taking the time to review the article and making these recommendations. I have responded below.
Point 1. I did actually try to resolve that by locating review papers on pubmed but was unsucessful. I could resolve it but would need to use multiple secondary sources. Actually an idea has popped into my head, I have a text book on benzodiazepines, a reliable one. It is written by Roche pharmaceuticals (I think). The entire book is about benzodiazepines, it is bound to cover these issues in the first paragraph, I just hope that I can locate them easily without having to read the whole book LOL. I shall see what I can do. Got mixed up when half asleep, thought you were talking about the first ref. Anyway I shall see what I can do about this over the coming days. I think that it can be resolved.--Literaturegeek | T@1k? 14:40, 7 June 2009 (UTC) I have removed the old 1999 review.--Literaturegeek | T@1k? 12:04, 8 June 2009 (UTC)
Point 2. I can get more recent citations for long term effects but unfortunately they would be primary sources I think. Very little research money is given to study long term effects of benzos, much of the research was carried out back in the 90's. I would be of the opinion that the citations should stay if they cannot be replaced with more recent secondary sources. Perhaps we could remove it from the lead though and just discuss it briefly in the article body somewhere?
Point 3. Done. Resolved, sources now cited in article body. Improvements have been made in finding more recent sources but as discussed this is not always possible for certain aspects of this article.
Point 4. Done. Resolved this issue.
Point 5. Done. I have replaced citation with a citation to the British national Formulary.
Point 6. Done. Deleted the primary source.
Point 7. Done, I deleted it. I am not aware of any update to the guidance of 1980 by the MHRA or related bodies, well there was actually a small update in 1988. The problem is these regulatory bodies only do updates if they believe the evidence base has changed or their views have changed and need to be revised. If they don't think policy needs changing they just leave things as they were. How do we resolve things like if current national guidelines are based on old reviews? I say they are current because the BNF, Department of Health still use these guidelines so they are current in that they are still functional review and guidance but only because it hasn't been updated. I think that we should stick with that until it is updated by the MHRA.
Point 8. I know very little about veterinary medicine and am not much more than a layman. I also do not have access to any vet books. Is there a wiki vet project that we could contact? Otherwise I think that improving these issues is not going to be very fruitful. perhaps we should delete the vet section. I dunno if I want to do that but if it is not possible to resolve it and the section is holding the FA back, oh well maybe it will have to be deleted. Done. (by somone else).--Literaturegeek | T@1k? 00:27, 14 June 2009 (UTC)
Point 9. Done. Resolved by someone else.--Literaturegeek | T@1k? 00:27, 14 June 2009 (UTC)
Point 10. Done. Resolved by someone else.--Literaturegeek | T@1k? 00:27, 14 June 2009 (UTC)
Point 11. Done. I deleted the hallucinogenic intoxication ref.
Point 12. The problem with citing crime data is that these types of data are compiled usually by or on behalf of governments rather than clinical researchers so review papers are hard if not impossible to track down. Done. Resolved by drastic shortening of section to a single sentence to remove undue weight issues.--Literaturegeek | T@1k? 00:27, 14 June 2009 (UTC)
Point 13. Partially resolved. Deleted the ref. Other point regarding use as muscle spasm of various causes can be treated with diazepam is a good point. Should we use the BNF as a citation for this?
Point 14. I do have to admit that I sometimes add 2 or 3 sources together. The reason is because is sometimes people challenge single refs as being "only the opinion" of one book, one author or group of authors etc. So sometimes I think that it is necessary if covering an area not widely known or even perhaps controversial or as noted earlier just to make the sentence or paragraph more comprehensive by including additional data, due care though needs to be taken not to do OR of course. Oh and another reason (perhaps bad habit or is it good?) is I tend not to edit articles by putting refs in middle of sentences like after a comma and prefer to add them both to the end of the sentence.
Part of the reason the side effects is full of citations is actually because of this review process as there were disputes over sources and which ones were the best etc. Although there were several refs used even before the FA review but they have doubled since it I think.--Literaturegeek | T@1k? 15:09, 7 June 2009 (UTC)
All valid points Colin. I agree with you that we really don't need to use primary sources for the article but I am not sure if we can achieve 100% no primary sources in the article without article content suffering. There are certain aspects of benzos which are not regularly reviewed or even extensively researched or regularly updated and thus finding recent reviews for certain aspects of benzos is not always possible in my opinion. The crime stats is the first thing that jumps to my mind as something which is rather difficult to find review articles as it is mostly gov reports and stuff and not discussed or reviewed or undergo meta-analysis in the literature for a number of reasons which I can explain if necessary. I do think that primary sources though should be debated and almost always if not always removed if a more review paper exists for that aspect of a subject and if agreed on talk page. I have deleted a couple already that you have suggested and more will probably deleted.
Ok those are my opinions which may be a bit blurred as I am half asleep. I will look forward to other's comments on the FA.--Literaturegeek | T@1k? 22:41, 6 June 2009 (UTC)
Mostly agree with Colin's comments. Except for two points. First, as he himself noticed "we are dealing with an mature class of drugs for which there is an abundance of high quality literature.". However, that means that the reviews tend to be older, and a 10-15-year-old review on benzodiazepines is often as fresh as it gets. If it is hard to find a review, WP policies do allow the judicious use of primary sources to improve the article. Second, the problems he noted are relatively easy to fix so, IMHO, they do not kill the nomination. The Sceptical Chymist (talk) 00:39, 7 June 2009 (UTC)
Just to point out I think that I got mixed up and thought Colin's point 1 was talking about the first ref. I did warn that I was half asleep when I wrote the above though! :)--Literaturegeek | T@1k? 14:40, 7 June 2009 (UTC)
I have rewritten parts of my responses to Colin with a more awake mind as well as updated some of the problems raised as resolved/done. So if you read my half aasleep response, please reread the updated "awake" response to Colin. :)--Literaturegeek | T@1k? 14:40, 7 June 2009 (UTC)
Thanks for your detailed response, Literaturegeek. Wrt the use of primary research papers: they are not absolutely forbidden but they should be used (if at all) to describe what that research found, or aspects of the study, not because of some fact they mention in their introductions, or to say "this is current clinical practice" when actually it was the particular circumstances set up for the study.
The vet section has been rewritten with appropriate sources.
I appreciate your problem that some research is no longer being conducted, so the studies and the reviews of those studies might be ageing. I'm no subject-expert here so I'm pointing out these are alarm bells when reviewing sources, but you may well have justification for having to use older papers. Some sources like Cochrane reviews or government/professional-body clinical guidelines are regularly renewed so even if the evidence and conclusions and text hasn't changed, the review/guideline might indicate that it has been recently checked as current. Other sources like academic monographs and professional textbooks are often regularly re-issued in new editions: these could be used more in this article I'm sure they would cover the subject to sufficient depth for this article's purpose. You might need to find a collaborator with access to a university library, if you don't yourself.
Wrt 3/4/5 citations strung together: it is not the job of the Misplaced Pages article page to prove the fact to the reader. For a given fact, cite the best source we can find. If someone queries the source, discuss this on the talk page and if necessary, replace the source. But don't keep adding in the hope it makes the argument stronger. Also, citing several authors to make the point that "X is widely held to be true" is verging on WP:OR. Instead, find a source that says that many/most authorities believe X to be true.
The "mechanism of action" section is improving but hasn't reached the level of clarity and accessibility I would hope to find in an FA. The lead sentence's "GABAA receptor" "modulation" is likely to kill a lay reader's confidence that they will be able to follow this section. Start with an overview sentence or two that says in complete layman's terms what these drugs do (look up some websites, charity sites, patient info leaflets ). Then introduce the reader to sufficient brain anatomy/chemistry that they can understand how GABA/benzos affect neuron firing. Then explain how this affects anxiety/seizures/muscles/etc. If there are aspects of "how they work" that science doesn't know, then say so (sourced, of course). Why are some benzos better at one property than some others? Why does diazepam relax muscles when other sedative/hypnotics do not? Why might some people get a "paradoxical" reaction? Colin° 19:36, 9 June 2009 (UTC)

You are welcome Colin. Agree with the need for caution when using primary sources. Here is the 1988 ref by the CSM. There hasn't been any update for the benzodiazepine drug class that I know of. Of course there are publications all the tiime debating this and that particular aspect of benzos back and forth but as far as national guidelines by the likes of the MHRA I am not aware of any update since 1988. I did research their site using keyword benzodiazepines and all I found after 1988 was a few sentences recommending an update to product/patient information leaflet for indivudal drugs regarding drowsiness and driving increase road traffic accidents or something like that. Individual patient information leaflets are regularly updated though. I understand what you are saying that it is not the job of wikipedia to prove poinnts to the reader and agree. What about other reason? One thing about review papers is often they only briefly skim over the aspect that you want to cite. What about using 2 or even 3 refs if you want to make the wiki article more comprehensive for the reader? What if article content suffers by only using one source for a paragraph?

Regarding how benzodiazepines work/mechanism of action who boghog seems to be enthusiastically improving :). I think Prof Ashton did a pretty good job in The Ashton Manual of writing about how benzos work in easy to understand terminology but whilst also describing it from a professional perspective. Read this to get an idea of tone and wording.. Dunno if this will help give a few ideas of how to make the mechanism of action section both informative to the professional but also informative to the lay person.--Literaturegeek | T@1k? 22:51, 9 June 2009 (UTC)

One other point is that there really isn't a whole lot of difference between the benzos at least not the 1,4 benzos. Most if not all commonly prescribed benzos will relax muscles, act as hypnotics, anxiolytics etc. If someone was convulsing and spasming and a doctor only had temazepam available, administering it would alleviate or reduce seizures, spasming for example and would also relieve anxiety. Prescribing indications are primarily motivated on pharmacokinetics and potency of the benzodiazepines and potency of available doses but also by what the manufacturers decide to market the drug on as. Speed of crossing the blood brain barrier as well is important for emergency situations. I don't think that it is worth discussing subtle differences between benzos unless it is just such as speed of crossing the blood brain barrier and also potency of benzos. There are some benzos which are metabolised into partial agonists and also atypical benzos eg clobazam which are more selective for certain receptors but think this info if it can be located would really be more relevant for the individual drug pages unless we find a good review paper which says that these differences are relevant.--Literaturegeek | T@1k? 23:10, 9 June 2009 (UTC)

RE: Stringing citations. Sometimes one thing is discussed in one review, and second in another, and first and third things in the third review. You have a sentence that talks about things 1,2 and 3. It is easier and more readable to put all three references at the end of the sentence. The Sceptical Chymist (talk) 01:20, 10 June 2009 (UTC)

This article and its sources have improved greatly. I've struck many criticisms and most of those that remain are significantly reduced, possibly to the point of not being a barrier. I'm left with three weaknesses.

  1. There are areas where the important facts are lost among the lesser. This probably occurs with a desire to be comprehensive and please everyone; laying fact upon fact is good for building an article -- but eventually you need to revise and refine. An example is the indications section where it is not always clear what indications are evidence based, what are common for good or bad reasons, what are uncommon due to rarity, what are uncommon due to being second or last choice, etc.
  2. The prose still needs a good going over. I've tweaked a little but I'm an amateur. There are sentence structures that seem awkward or illformed to me but I'm not able to confidently revise. I suggest you find someone with good writing skills and collaborate with them (for you may have to correct their factual mistakes, or supply alternative wording based on sources only you have access to).
  3. The Pharmacology section is still a level too advanced for WP. Helping the reader understand this may bloat the section to the point that a daughter article could be required, leaving this section less detailed.

Colin° 21:02, 16 June 2009 (UTC)

The indications listed I think do have an evidence base and are licensed indications for benzodiazepines. As far as first line and second line, I dunno if we start going into that much detail we will end up describing the treatment of anxiety, treatment of mixed anxiety and depression and treatment of insomnia. Is this not more relevant to anxiety disorder pages or insomnia page (which I have contributed a little to anyway in this regard on those pages). I think we risk going too much off-topic if we start discussing too much detail on what should be tried first for each indication.

I have just done some work has been done on the prose so hopefully this has been resolved? I am not sure what else needs to be done.

The chemistry section is always going to be technical if someone doesn't understand molecular chemistry. I don't believe that can be simplified. The mechanism of action section has an introductory paragraph which I feel the lay person will understand the basic gist of how benzos work, i.e. they help "calm" the nervous system. I don't think that it does any harm to then explain some of the technical details which the reader can skip if they wish although they may be able to get the general gist of what is being said from the intro parragraph. I think having some technical details gives the article a bit of credibility making it professional.--Literaturegeek | T@1k? 18:42, 17 June 2009 (UTC)

No, it's a new, clean slate: just like a new nomination. If you want to bring forward any unresolved issues from the previous nom, it might be better to take them to article talk so that this page won't become so unwieldy again. SandyGeorgia (Talk) 00:50, 7 June 2009 (UTC)
  • Comment. Concerning Colin's statement that 'the "Mechanism of action" section is utterly impenetrable', I have added a somewhat less technical introduction to the subject which I hope makes the section more accessible to the general reader. The general mechanism is known (benzodiazepine → GABAA receptor → increased GABA binding → increased chloride current → increased membrane potential → inhibition of neuronal firing). Furthermore I think it is rather intuitive that inhibition of neuronal firing in the brain would lead to the constellation effects that benzodiazepine possess. However it has not been entirely worked out which specific GABAA receptor subtypes control which specific neurons in which specific parts of the brain to mediate the anxiolytic vs. sedation/hypnotic vs. muscle relaxant vs. anticonvulsant effects of benzodiazepines. Hence it is not possible to pinpoint the exact mechanism of sedation for example, even though the general mechanism of benzodiazepine's pharmacological action has been worked out. Boghog2 (talk) 19:53, 7 June 2009 (UTC)
  1. Introductions summarizing content in sections with multiple subsections usually make articles much more accesible for lay readers. I believe they should be added in the sections that do not have them (Special populations and pharmacology).: (I have finally done it myself)
  2. Lolk 2006 article is in danish: I am sure there are plenty of reviews on benzos in elderly in english.
  3. The article is probably overlinked: MOS states that words should only be linked the first time they appear.

I did add intro type sentences too some of the sections as requested but they ended up getting deleted as being redundancy. A problem I am finding which is probably unavoidable is that each reviewer is going to have at least slightly different and conflicting views on what the article needs done to it to reach featured article.--Literaturegeek | T@1k? 10:38, 8 June 2009 (UTC)

I have deleted the Lolk review, it was unnecessary anyway as another review said the same thing pretty much. I did not know foreign language papers were not acceptable for featured articles. Sorry about that.--Literaturegeek | T@1k? 10:38, 8 June 2009 (UTC)

I will when I get a chance go over the wiki links to remove any overlinkage.--Literaturegeek | T@1k? 10:38, 8 June 2009 (UTC)

4 Comments

  • Colin's great re-write of the therapeutic use in seizures mentions all the main anti-seizure benzodiazepines in the body of the article. That means that the list on the right with Main anticonvulsant benzodiazepines is not needed and can be deleted. The challenge now is to get rid of the two other unsightly items -- Main anxiolytic benzodiazepines and Main hypnotic benzodiazepines -- by working 3-4 of the most often used into the body of the corresponding chapters.
  • Epidemiology/Utilization section/paragraph is still needed
  • Drug misuse section still has to be copyedited
  • I wonder if FV knows where to find or maybe can draw a 3D picture of the GABA-a receptor. It is pretty and would be a nice illustration. Unfortunately, all the pictures I saw were copyrighted.

The Sceptical Chymist (talk) 10:29, 8 June 2009 (UTC)

Epidemiology is going to be rather difficult to get because governments don't track benzo prescribing figures. They know how many prescriptions are issued each year and some people have made rough guesstimates of how many are long term users. A popular figure is between 1.2 million and 1.5 million in the UK are on benzos long term based on like s survey of an "average sized GP practice" multiplied by total of GP practices in the UK. That is how it is calculated. Not very accurate. Figures for short term users would be even more difficult if not impossible to get. Then you run into t he problem of people claiming article not being a world view of the subject matter and wanting stats for their countries included etc etc which aren't available. I can see utilisation causing more problems than it would solve. If national govs tracked number of people taking benzos it would be a great idea.--Literaturegeek | T@1k? 22:51, 9 June 2009 (UTC)

There are two 3D schematic representations of the GABAA receptor in the GABAA receptor article. If you would like either of these specifically modified for the benzodiazepine article, let me know. I am open to suggestions. Cheers. Boghog2 (talk) 14:34, 8 June 2009 (UTC)
Actually, the 2-D representation seems to be most instructive . What do you think about adding it to the article? The Sceptical Chymist (talk) 00:51, 9 June 2009 (UTC)
Good suggestion and therefore I have inserted the 2D figure. Boghog2 (talk) 04:56, 10 June 2009 (UTC)
  • Comment: In line with Sceptical chymist I think that lists of main xxx benzodiazepines are not appropiate. They are unesthetical, probably unencyclopedic (I doubt any reader has an interest in knowing all of them) and also at this point original research, since no reference is provided to support that they are the main ones used for each problem. I feel that not much would be lost if they are simply eliminated (although it would be even better to integrate them in text). I also want to say that I feel that great improvements are being attained and to thank the effort of the main editor and several reviewers in this line.--Garrondo (talk) 14:03, 8 June 2009 (UTC)

I have deleted the tables. I agree with the original research problems of the tables. :)--Literaturegeek | T@1k? 01:08, 9 June 2009 (UTC)

Oppose—The prose needs a good going through, entirely, by an unfamiliar copy-editor.

  • Don't professionals commonly refer to them as "benzos"? I'd be inclined to put this in as a common term in parentheses at the opening.
  • "Elimination half-life"—Bizarre term, since elimination is normally considered to occur at something like four or five times the half-life. Half is eliminated ... hmmm ... hard. But if it's standard, what can we say?
  • "... being categorized as either short-acting, intermediate-acting or long-acting. Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia. Longer-acting benzodiazepines are preferred for the treatment of anxiety." Can't we make it neater, like this? "being categorized as either short-, intermediate- or long-acting. Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia; longer-acting benzodiazepines are preferred for the treatment of anxiety." Note the semicolon. You've used the reverse ellipsis anyway in the second sentence. Problem for me in "long-acting" and then "longER acting"; are you referring to the same characteristic?
  • Remove "now"?
  • "in the short term" (last two words are not a double adjective, so no hyphen—"term" is the noun). But then the reverse problem: "long-term use"; please pipe it, because the linked article was wrongly named (now redirected to an article where the hyphen IS there). Please see , if you wish.
  • This is a bombsite, I'm afraid: "uncertainty remains whether they cause major malformations in a small number of babies". First, we need "as to". Second, is the uncertainty about the proportion of babies that suffer malformation for this reason? Maybe you mean ... well, I'm unsure what you mean. "The role of benzodiazepines in the major m in a s n of b is uncertain"?
  • "The first of its kind"—"The first benzodiazepine"?.
  • "Taken during gestation can however, cause neonatal withdrawal effects." Nope. What is being taken? Two commas required around "however" in mid-sentence, but better to start with H.,".
  • "such as alcohol or opiates": you're overusing "or", when you mean "and" in a simple list ("or" in English is very exclusive). Greatly ... particularly —a bit marked. Tony (talk) 16:33, 9 June 2009 (UTC)

I agree with benzos being included, it is a very widely used terms in the general public but even sometimes amongst professionals. If you take away the word elimination, a lay person is going to think "what is a half life?" but with the word elimination half life they are more likely to figure out that it is to do with metabbolism. Maybe we could change it to metabolic half life but maybe that is a bit of a, as we say in the UK, "dodgy" term? Some great suggestions for the lead Tony.--Literaturegeek | T@1k? 22:51, 9 June 2009 (UTC)

  • Comment. Colin's point about sources is a good one. I've tried to catalog the extent of the problem in Talk:Benzodiazepine #Catalog of sources. Briefly: most sources are quite good. However, there are 19 primary studies, many old; there are 30 reviews more than ten years old; and 1 confidential document and 1 letter to the editor are not needed. Eubulides (talk) 02:22, 10 June 2009 (UTC)
Wow! That is really thorough and useful list. Thank you The Sceptical Chymist (talk) 10:15, 10 June 2009 (UTC)
Agree. That must have taken some time and is immensely valuable. Thanks very much. Colin° 10:47, 10 June 2009 (UTC)
You're welcome. All but one of the primary sources have now been removed and the remaining source, Loxley 2007 (PDF), is arguably OK and in any case is carefully summarized. As far as sources go, the remaining problem, as I see it, is citation of too many old reviews, dating back to 1981. Anybody care to take a crack at that? Talk:Benzodiazepine #Recent reviews that may be worth citing lists some good recent reviews, many of them freely readable. Eubulides (talk) 10:03, 12 June 2009 (UTC)
  • Support. The article is not ideal but deserves to be promoted. Most of the concerns have been addressed, and the article has made huge progress since it was first nominated. It does represent the finest of the Misplaced Pages work. For example, a comparison of Benzodiazepine with its closest peers -- the only two featured articles on a class of drugs -- is very much in favor of Benzodiazepine. One such article, the FA Antioxidants is long, lacks internal logic, is all over the place, and full of unnecessary details and specialist jargon. Another one, the FA Anabolic steroid has multiple tags and does not follow guidelines -- it even does not have the Indications chapter. In contrast, Benzodiazepine follows guidelines, is properly referenced, is not overly long, avoids jargon (except where appropriate), is written reasonably well, and addresses the most important things first before specialist chapters like Pharmacology. The Sceptical Chymist (talk) 23:54, 11 June 2009 (UTC) Withdrawn. Oppose. Unfortunately, after I gave the article my support, the nominator re-introduced the POV issues related to the side effects of benzodiazepines. The particular issue is the controversy regarding benzodiazepine tolerance and long-term effects. A significant number of psychiatrists (it may even be a majority) believes that the long-term effects of benzodiazepines are relatively mild and tolerance to their main therapeutic anxiolytic action may not develop. The Sceptical Chymist (talk) 21:45, 20 June 2009 (UTC)

I think that the article is much improved and would like to see it promoted to FA but can't vote due to a large amount of work done to the article prior to FA review. I believe it has reached FA status.--Literaturegeek | T@1k? 01:36, 13 June 2009 (UTC)

I have updated my list of points in response to Colin's points. I believe that I and others have resolved Colin's points although if any point has not been resolved satisfactorily let me (us) know. :)

Thank you everyone for your hard work on rreviewing this article. :)--Literaturegeek | T@1k? 00:27, 14 June 2009 (UTC)

Thank you for supporting Garrondo and Sceptical. Hopefully Colin will also support the article now or if not will let us know what else is remaining.--Literaturegeek | T@1k? 00:29, 14 June 2009 (UTC)

Ok, more improvements have been made to the article. I think all issues have been addressed effectively. Can I ask who supports and who opposes the article going to FA status? Thank you again everyone for all of your hard work on this article. :-)--Literaturegeek | T@1k? 16:40, 14 June 2009 (UTC)

Unresolved opposes still from Tony1 and Colin. SandyGeorgia (Talk) 02:56, 16 June 2009 (UTC)
Colin's items 2,3 and 7 regarding the age of the references have been discussed extensively here and on the Talk page. The bottom line: research on old drugs is sluggish, the most relevant and detailed references tend to be old because there is nothing to update them with. The newer reviews often simply regurgitate the conclusions of the older reviews. In such circumstances the demands for fresh reviews are onerous and unrealistic. The Sceptical Chymist (talk) 03:29, 16 June 2009 (UTC)
Many (or maybe even all) of Tony's opposes have been addressed. I think he just have not visited this page recently to cross them. The Sceptical Chymist (talk) 03:32, 16 June 2009 (UTC)

A large number of the old reviews were updated but some were not changed as newer sources were not available. I believe Colin was satisfied but has raised some additional points which I am going to address today. A number of Tony's problems have been addressed but will try and address the unaddressed ones today as well.--Literaturegeek | T@1k? 09:39, 16 June 2009 (UTC)

  • Comment Support. I supported this article in the original go-round, and it has improved in many ways since then. However, there is still at least one significant POV and summarization issue, with no resolution despite my repeated attempts (see Talk:Benzodiazepine #Paton 2002), and I cannot support it yet. I've tagged the relevant section, until we can resolve the disagreement. Also, Colin's and Tony1's comments weigh heavily with me: the article has changed quite a bit and clearly needs a copy-edit, but before that, the sourcing needs to be improved. In terms of sourcing older and/or primary sources, I fear that the article has gone downhill since I last cataloged the sources (in Talk:Benzodiazepine#Catalog). Eubulides (talk) 08:51, 17 June 2009 (UTC) Previous problems have been fixed. A further copy-edit would help (where's Tony1 when you need him?), but the article is already of FA quality. Eubulides (talk) 07:46, 18 June 2009 (UTC)

"the sourcing needs to be improved" and "In terms of sourcing older and/or primary sources, I fear that the article has gone downhill since I last cataloged the sources". What??? I see that you and Sceptical ended up getting into a fight on article talk page. You are now claiming that this article has sourcing problems when it is 99% secondary sources with most old reviews wherever possible replaced with new ones which in turn led you to supporting the article. I am concerned that because you had a falling out with Sceptical over the paradoxical section that you are now wrongly claiming (perhaps in temper) the article has "gone downhill" in terms of primary sources and older reviews when in reality all but one primary source has been removed and the majority of the older reviews have wherever possible been replaced with newer sources and you were happy to support it.

I don't think either you or Sceptical were interpreting things accurately. I edited the paradoxical section and believe that I have resolved the dispute. I would appreciate it if you would retract your statement that implies that the issue of use of primary sources and older reviews has gotten worse when you know that that issue has been resolved. Why did you make this statement above?--Literaturegeek | T@1k? 21:07, 17 June 2009 (UTC)

I do appreciate all of your work in categorising all of the sources according to year of publication and whether they are primary sources or review articles. Please try to appreciate that when I spend hours upon hours upon hours resolving these issues to then see because you and another editor had a fight over a couple of sentences you claiming inaccurately perhaps in temper that this issue hasn't been resolved but has got worse when you know it is resolved is very frustrating.--Literaturegeek | T@1k? 21:14, 17 June 2009 (UTC)

The dispute was resolved after I made my comments about sourcing and POV. I've now struck those comments and changed the "comment" to a "support". Thanks for all the work you've done on the article. Eubulides (talk) 07:46, 18 June 2009 (UTC)

Thank you Eubulides for clarifying and clearing this up. Much appreciated. I just didn't want other reviewers to get the wrong impressions of the article. :)--Literaturegeek | T@1k? 12:35, 18 June 2009 (UTC)

All issues resolved

I have done extensive work trying to resolve all issues raised here. I believe that they are all resolved or where I or others disagreed was explained why. I have resolved the issues raised by Eubulides, Colin and Tony1. If you feel issues still have not been resolved and could be please type below so that they can be resolved or else discussed. Please also cross out resolved issues in any comments that you have made. If you do not support the article please explain why. Thank you again for everyones hard work.--Literaturegeek | T@1k? 21:22, 17 June 2009 (UTC)

Snowman, I have read through this a couple of times - alot of it is quit technical I agree. Can you please give some examples and we can try and fix? Casliber (talk · contribs) 13:46, 18 June 2009 (UTC)

I think that the problem is the prose and not the technical nature of the subject matter. Looking at one section on "Alcohol withdrawal": Snowman (talk) 15:03, 18 June 2009 (UTC)

  • The difference between a planned controlled reduction of alcohol in motivated outpatients, which should probably be called "detox" (or alcohol detoxification) and "alcohol withdrawal syndrome" are confused. Snowman (talk) 14:46, 18 June 2009 (UTC)
  • I thought that clordiaxepoxide was in fashion in preference to diazepam in detoxification, because clordiazepoxide is less addictive. Snowman (talk) 14:46, 18 June 2009 (UTC)
  • "Their long half-life makes withdrawal smoother and rebound symptoms less likely to occur." I would have put something like; "The benzodiazepines with a longer half life make detoxification more tolerable and dangerous alcohol withdrawal effects less likely to occur." Perhaps adding something about benzodiazepines being addictive themselves, and the historical use of the chlormethiazole. Snowman (talk) 14:46, 18 June 2009 (UTC)
  • "They are thus not recommended for outpatient detoxification." This statement should be more clearly linked to the shorter half life benzodiazepines, as chlordiazepoxide is use for out-patient alcohol detoxification and taken orally four times per day. Snowman (talk) 14:46, 18 June 2009 (UTC)
  • "Rebound effects are more likely with short-acting benzodiazepines, especially if they are not tapered after alcohol detoxification." This does not specify if the "rebound effects" are of alcohol withdrawal or benzodiazepine withdrawal. The term "alcohol detoxification" is used for the first time in this paragraph and pops up at the end of the sentence, which adds to the confusion about what this section is about - "alcohol detoxification" or "alcohol withdrawal syndrome", or, if it is about both the two, they are confused. Snowman (talk) 14:46, 18 June 2009 (UTC)

Looking at the section on "Other indications": Snowman (talk) 15:03, 18 June 2009 (UTC)

  • "severe pain". Not a notable use, I would have thought. Needs to put this is context of co-prescribing, or remove it. Snowman (talk) 15:03, 18 June 2009 (UTC)
  • "They bring about anxiety relief and also produce amnesia; which can be useful in this situation, as patients will not be able to remember any unpleasantness from the procedure." For most benzodiazepines the anxiety (should have said "amnesia" - corrected at 19:38, 18 June 2009 by Snowman) is not absolute, I would have thought. Medazolam may need a special mention, in its capacity to induce anmesia an as a premed for endoscopy (including gastroscopy) day cases, and other day case interventions. Snowman (talk) 15:03, 18 June 2009 (UTC)
  • "Some examples include the treatment of tetanus and stiff person syndrome which is a neurological disorder characterized by severe muscle stiffness." Some uncommon or rare disorders here, and I do not think that you get many points for mentioning these before benzodiaepines in thyrotoxicosis. Snowman (talk) 15:03, 18 June 2009 (UTC)
You have made some good points, I need to sleep, but there are quite a few interested in polishing this article up. It was always going to be a big one to do. Casliber (talk · contribs) 15:13, 18 June 2009 (UTC)

The section on "Elderly": Snowman (talk) 15:21, 18 June 2009 (UTC)

  • "Chronic effects of benzodiazepines and benzodiazepine dependence in the elderly can resemble dementia, depression or anxiety syndromes, which worsens over time." What worsens over time? Snowman (talk) 15:21, 18 June 2009 (UTC)
  • The image draws attention to the caption: "Adverse effects of benzodiazepines are increased in the elderly. These adverse effects are often mistaken for the effects of old age." Please specify which "adverse effects" are referred to and provide a reference. Snowman (talk) 15:21, 18 June 2009 (UTC)

I think that the wicket favours critical reviewers. In summary I see problems with the prose almost everywhere I look, and my impression is that the article is nowhere near a FA grade. I suspect that everything will need to be copy edited again and again, word by word, and line by line. Snowman (talk) 15:21, 18 June 2009 (UTC)

I disagree that alcohol withdrawal and alcohol detoxification are confused. The reason that benzodiazepines are prescribed during alcohol detoxification is to manage alcohol withdrawal symptoms or syndrome.--Literaturegeek | T@1k? 17:25, 18 June 2009 (UTC)

I think "alcohol withdrawl syndrome" and "alcohol detoxification" are confused. It might happen, but I would not normally expect a person undergoing elective "alcohol detoxification" as an to have a fit as part of "alcohol withdrawal syndrome" whilst on a therapeutic reducing schedule of chlordiaxepoxide tablets, as the medication should prevent this. Fits, alcohol withdrawal syndrome, and "alcohol detoxification" are all mixed up in the same paragraph. Could delirium be confused with "Korsakoff's syndrome"? - the treatment for that is thiamine. Would it be better to say "subdue delirium"? Again I would not normally expect someone undergoing elective outpatient or inpatient therapeutic "alcohol detoxification" to have much in the way of delirium. "Alcohol withdrawal syndrome" can be severe and the severe end has a mortality. Snowman (talk) 19:22, 18 June 2009 (UTC)

I have seen people who have had delerium tremens in a hospital environment despite chlordiazepoxide therapy and was required lorazepam injections to partially relieve it although it is not a typical scenario. Are you saying that you want the terms alcohol withdrawal deleted and replaced with "alcohol detoxification" or just the title of the section changed to alcohol detoxification? I am still not sure that I am following you. Perhaps you should edit the problematic terminology of this section?--Literaturegeek | T@1k? 20:55, 18 June 2009 (UTC)

OK, I have copy edited that section. Snowman (talk) 22:34, 18 June 2009 (UTC)

Chlordiazepoxide is more commonly prescribed for alcohol withdrawal at least in the UK and USA (not sure about other countries). Diazepam is however, a better anticonvulsant so may be preferred by some clinicians for managing alcohol withdrawal. I have referenced that chlordiazepoxide is the most commonly prescribed benzo for alcohol withdrawal.--Literaturegeek | T@1k? 17:52, 18 June 2009 (UTC)

  • I had a niggling doubt wondering what might be used all over the world. Anyway, both diazepam and chlordiazepoxide are reasonably cheep drugs in the west it seems. I suppose "non phamacology" is used most for mild problem drinkers giving a verbal warning about the bad effects of alcohol and advice drinking less. I think drugs would be used at the more severe end of drinking problems. Snowman (talk) 19:18, 18 June 2009 (UTC)

I have resolved next point, reworded sentence using your preferred wording and I also added about the risks of dependence. I am not sure it is worth mentioning about chlormethiazole. It is so very rarely used today, I think it is going too off-topic unnecessarily. I think that it might be relevant to the alcohol related articles though. I started to add about chlormethiazole but then realised I needed to explain to the reader that it wasn't a benzo and then make it relevant to the reader and it really would bring up undue weight and irrelevance to the article section I feel so would rather not add about chlormethiazole. It is certainly relevant from a historical perspective to the alcohol related wiki articles though.--Literaturegeek | T@1k? 18:27, 18 June 2009 (UTC)

I believe that I have resolved your next point regarding the short acting benzos not being recommended in ouutpatient detoxification. It is now cleear to the reader that the sentence is only referring to short acting benzos.--Literaturegeek | T@1k? 18:44, 18 June 2009 (UTC)

I resolved the issue by just deleting the bit about rebound effects as it was confusing if it meant alcohol withdrawal or benzo rebound.--Literaturegeek | T@1k? 19:20, 18 June 2009 (UTC)

Severe pain was deleted so this issue is resolved.--Literaturegeek | T@1k? 19:20, 18 June 2009 (UTC)

I am not sure what your complaint is regarding anxiety not being absolute etc. Some patients are anxious and some aren't, if they are anxious then a benzo often midazolam can help. If proceedure might be traumatic the amnesia effects help. I don't see what you are saying is wrong with that section or paragraph?--Literaturegeek | T@1k? 19:23, 18 June 2009 (UTC)

Whoops, I meant to say "amnesia" is not absolute. I have struck "anxiety" out and added "amnesia" afterwards. Snowman (talk) 19:39, 18 June 2009 (UTC)
I think of my remarks as "helpful comments" which I hope can advance the discussion here and lead to improvements in the article, and not as complaints. Snowman (talk) 19:51, 18 June 2009 (UTC)

Whoops, sorry I didn't mean to impply negativity by using the word "complaint". I didn't view your remarks as negative but as productive criticism and productive suggestions which are helping to improve the article.--Literaturegeek | T@1k? 20:45, 18 June 2009 (UTC)

Thank you. Snowman (talk) 22:34, 18 June 2009 (UTC)

I believe that I have resolved the issues that you have raised regarding the elderly sections.--Literaturegeek | T@1k? 20:45, 18 June 2009 (UTC)

I think that the side effect of amnesia (or therapeutic effect in this situation) could be achieved with all benzodiazepines if a high enough dose was given. Some benzos are lower potency pharmacodynamically speaking or else just marketed in low potency doses or both which can largely be overcome by giving/taking higher doses of the benzodiazepine. AAnyway have expanded that section using the British National Formulary as a ref.--Literaturegeek | T@1k? 19:51, 18 June 2009 (UTC)

Anyway, I am not sure what premeds are given these days. But the article seems to suggest that when a benzodiazepine premed is given the patient immediately forgets everything. Amnesia might be achieved quite quickly with IV high does medazolam or lorazepam, but what if the aim of the premed was to reduce anxiety and it was given in a lower dose perhaps orally the evening before or prior to a ga. I think most patients normally remember going into anaesthetic room prior to g.a. surgery, but they might not remember much about a endogastroscopy (not g.a.) after iv benzodiaepine. Snowman (talk) 20:42, 18 June 2009 (UTC)

That would like you say depend on the dose and route given for the benzo. It would also depend on what were the desired effects that the treating clinician and patient wanted.--Literaturegeek | T@1k? 20:58, 18 June 2009 (UTC)

I deleted rare indications for benzodiazepines for muscle spams. I did a search for thyrotoxicosis and only found a single secondary source for benzos for this indication and it was from 1971 and had no abstract. i spoke to a doctor and enquired about what is usually used for chronic conditions with muscle spasms and was told that it was usually baclofen that is used. I assume that this is because tolerance does not occur with baclofen like it does with benzodiazepines and thus baclofen is a better treatment option long term.--Literaturegeek | T@1k? 20:02, 18 June 2009 (UTC)

  • "Mehta DK (2009). "4 Central Nervous System". British National Formulary (57th ed.). BMJ Group and RPS Publishing. pp. 183–264." The page range is much too large for quick verifiability, and I think this is unsatisfactory at FA, especially as the book is divided into smaller sections. I have the book and it would be easier to verify, if you put actual page numbers or smaller sections like "section 4.1.1." for each reference point. Why have you put "Mehta DK (2009)". I could not find this person in the long list of contributors, nor any attribution to chapter 4. Snowman (talk) 18:55, 18 June 2009 (UTC)

I can resolve this issue but this means having several references to the same book and chapter but just with different pages. The BNF has a list in the back for tracking down info for alcohol withdrawal, hypnotics anxiolytics so it is not like regular books in that regard so don't think that verification is a problem for anyone who has access to the British National Formulary. Can you confirm that you are ok with having several refs to same book and chapter but just more specific pages? I am just concious of trying to resolve one minor problem but creating more problems.--Literaturegeek | T@1k? 19:20, 18 June 2009 (UTC)

Yes, I think it is worth doing otherwise it could take ages to verify parts of the text and provide proof for a correction. I can not be guessing at where the information came from anywhere from pages 183–264. Someone else asked for more information on this too. There is a way of listing more than one ref on different pages in a book with a "Cited texts" section, and just putting the book and page number in the list of notes. Look at another page where this is done before doing a lot of work on it. Snowman (talk) 19:31, 18 June 2009 (UTC)
When there are many references to the same book, each to a different page range, it's better to have just one full citation to the book (this can be done in Further reading), with the remaining citations being to pages within the book, saying only "BNF 2009" or something like that. Please see Daylight saving time for an example. This sort of thing is quite common in the humanities (see Samuel Johnson for an extreme example, not that I'm recommending that style here!) and it works fairly well. Eubulides (talk) 19:49, 18 June 2009 (UTC)
I see what you mean; I do not think that many articles use a "Further reading" section for "Cited texts". There is a whole log of MOS on this. "Philip Larkin" is a GA to refer too. Snowman (talk) 19:58, 18 June 2009 (UTC)

I shall check out the "cited texts", after I have resolved your other points. Looks like a good option. Thanks.--Literaturegeek | T@1k? 19:51, 18 June 2009 (UTC)

I looked at the Philip Larkin and looked at how they did their cites. They didn't use the citation templates and just manually typed between ref tags book title and page number. I know if I follow that suggestion it will get opposed based on consistency of refs. Inline citations using citation templates are an important part of GA and FA articles. I think we need a different solution.--Literaturegeek | T@1k? 22:30, 18 June 2009 (UTC)

One can use citation templates to implement that style. Please see Philitas of Cos for an example: it has three sources used in lots of places (in the References section), with inline citations to specific pages or chapters of each source (in the Notes section). For example, the citation {{cite book |author=Spanoudakis |title= Philitas of Cos |page=26}} generates "Spanoudakis. Philitas of Cos. p. 26." in Notes, with the full citation appearing in References. Citations to other sources are given in full, and appear in Notes. All citations use citation templates. In other words, whether one uses citation templates is independent of whether one factors out full citations to books. This is a relatively minor point, and doesn't affect FA status, so perhaps I'll simply implement it if I find the time. Eubulides (talk) 00:27, 20 June 2009 (UTC)

Thanks but Colin was responsible for most of the work improving that section. I helped a bit to though. :)--Literaturegeek | T@1k? 19:20, 18 June 2009 (UTC)

Are we close?

I believe that I have resolved almost all of the problems raised by snowmanradio. I am still not completely clear on the problems in the alcohol sections (see discussion above). The other problem was the recommendation of using "cited texts" with in a single reference. I was unable to find any instructions on how to do this. Can anyone provide me with a wiki page which describes this? Are we close to going to FA status? If not, then what remains to be done?--Literaturegeek | T@1k? 21:07, 18 June 2009 (UTC)

I have copy edited the alcohol withdrawal section. Snowman (talk) 22:05, 18 June 2009 (UTC)
I think that the new referenced caption for the image of the old lady is good. Snowman (talk) 22:05, 18 June 2009 (UTC)
  • Being a medical article I feel that ambiguities need to be minimised. I have concentrated on four fairly randomly selected sections, to discover what state the article is in overall. My comments were not meant to be a complete list of problems in the article. Also, a reviewer above said that his list was not meant to be an exhaustive list of problems. One section I looked at was good, two sections have been tidied up a bit, and one has been almost completely rewritten. What about the rest of the article which I have not commented on? I think that the article needs a lot of improvements before it is near FA. Snowman (talk) 22:05, 18 June 2009 (UTC)

Thanks, I agree on the importance on removing ambiguities. The other sections though I feel are in a lot better shape than the ones you reviewed. I have requested the help of an experienced copy-editor (Matissee) who thank God has kindly agreed to help out with this article, as I am finding resolving the final issues very stressful. Hopefully she can help nudge the article forward towards a featured article status. :)--Literaturegeek | T@1k? 23:51, 18 June 2009 (UTC)

I was thinking about asking Matissee to help out too. I am glad that she has done some copy editing because I think she is very good with English grammar. I feel more relaxed already. Snowman (talk) 14:10, 19 June 2009 (UTC)

Issues resolved

Matisse appears to have finished copyediting the article, this I felt was the final issue that needed to be resolved. I feel that I have resolved the issues raised by reviewers. I really think that the article is up to FA standard and infact believe the article is of a higher standard than a lot of other FA articles (but I have a little bias hehe). I would kindly request reviewers to give the article a final review and either support the nomination or point out what remains to be done. I do appreciate the time and effort everyone has put into this article, reviewing it, making constructive criticisms and editing the article. :)--Literaturegeek | T@1k? 21:22, 19 June 2009 (UTC)

  • BNF page numbers have only just become available today, so I expect people will be checking them over the next few days. Could diazepam and chlordiazepoxide be included in the "Pharmacokinetics" section? Much is made of the half-lives of these drugs in the rest of the page, so it would seem reasonable to give them a mention in this section. Could the reference points be placed more directly with the text in this section to indicate where the information has come from? Snowman (talk) 23:16, 19 June 2009 (UTC)

Spot-checks on return. I've withdrawn my oppose, but there are still glitches. Further copy-editing, if this is promoted, would be welcome—there's not a lot to do, but it requires careful eyes to pick out the occasional ambiguities and looseness in the expression. I've made a few light copy-edits at the top.

  • "The first benzodiazepine, chlordiazepoxide (Librium), discovered accidentally by Leo Sternbach, was marketed from 1960 by Hoffmann–La Roche, who also marketed diazepam (Valium) from 1963." Can you insert "in "? I think I winkled 1955 out of the text below; seems kind of important (and an amazingly short R&D track). "who" --> "which", if you're referrring to Roche and not Sternbach.
  • There's a rule concerning "the": when there's an "of" on the right, use a "the" on the left. It's not incontrovertible, but it's the default. "Therapeutic properties of benzodiazepines are mediated by enhancing the effect of the inhibitory neurotransmitter ..."; needs to start with "The thera...": presumably you're referring to all of them, or at least all of the ones we commonly know about.
  • Are these equative or exclusive "or"s? "cognitive impairments or paradoxical effects such as occasional aggression or behavioral disinhibition occasionally occur." If the former, please use parentheses: "cognitive impairments (paradoxical effects) such as ...". I suspect the second occurrence is exclusive; if not, please use "and". "Or" is dangerous in English, I tell non-natives and natives alike. Another problem: do you mean they might "occasionally occur" in most or every patient? Probably not; if you want to convey that these are relatively rare, you might consider saying "occasional c. i. have been recorded/observed", or something like that. Sorry to be fussy. Tony (talk) 03:14, 21 June 2009 (UTC)

PS After conferring with User:Noetica, I think the best is: "Benzodiazepines are generally safe and effective in the short term, although cognitive impairments, or paradoxical effects such as aggression or behavioral disinhibition, occasionally occur." Still the issue of the last two words, though. Tony (talk) 03:55, 21 June 2009 (UTC)

  • "It has been argued that long term use of hypnotics and over prescribing of these drugs represents an unjustifiable risk to the individual and to public health in general, especially in the elderly." This seems to be an imbalanced comment. Who is arguing this? Presumably there is a counter argument. Are there exceptions and for who? How is over prescribing quantified? What is the unjustifiable risk to an individual? What is the unjustifiable risk to public health? Snowman (talk) 09:08, 22 June 2009 (UTC)
  • Much is made of the half-lives of chlordiazepoxide and diazepam in the article, but they are not included in the "Pharmacokinetics" section. Snowman (talk) 09:08, 22 June 2009 (UTC)

There really is no argument that hypnotics lose their benefits after a matter of days or weeks. Not even the drug companies argue that they remain effective because it is proven via EEG studies and the risks such as increased motor vehicle accidents and next day sedation aren't really disputed either. So really anyone advocating chronic benzo hypnotics would be arguing we should give these drugs even though they do not work and they would have to argue they are completely without any adverse risks. I will try and track down the full text of that article to get the more finer details of the unjustifiable risks. I would imagine it would be cognitive impairment, road traffic accidents and dependence. It is a bit like drinking a couple of pints and getting behind teh wheel would be a risk to public health.--Literaturegeek | T@1k? 19:05, 22 June 2009 (UTC)

  • Comment I support Snowmanradio's observations above and have added my own comments on the talk page. I think this article is near FA, but it seems to promote global, generalized statements that are accepted by the establishment but unsupported by the research literature on the long term risk/benefits of benzodiazepine use. —Mattisse (Talk) 13:03, 23 June 2009 (UTC)

I am finding the editing environment intolerable. I feel like I am under attack by medically illiterate people. For example I explained to Sceptical that CT scans don't measure neuron function but only measure brain structure changes. He either thought I was mistaken or ignored me and continued edit warring and denouncing refs based on his lack of understanding of what a CT scan is. Then Mattissa is attacking me with her original research for example, saying things like there is no way benzos could cause convulsions from abrupt high dose withdrawal and I am biased for even suggesting this, she had a "fit" when I mentioned this doesn't happen with opiates. Her evidence, things like well it is Schedule IV so therefore withdrawal has to be mild. I spent 5 or 6 hours refuting all of her original research with refs. She denounced National Statistics of drug related deaths as propaganda, implying some government conspiracy involving hundred of coroners faking lots of dead people and lab results. Furthermore a lot of these arguments were totally off-topic as I was not challenging the article content such as overdose section so it was a pointless argument. I feel under attack by scientifically illiterate people who have gotten ideas in their head. Today really is the final straw when Sceptical bombarded me with various wikipedia policies which really denounced his actions. He deleted a reffed sentence which I can actually add half a dozen or more refs to back it up if necessary so that only the view of tolerance doesn't happen when I had both views cited. He only wanted his one which was uncontrolled questionaire based trials. I can't work in this environment unless someone with some basic medical knowledge can come along to refute all of this gibberish like accusing me of bias for saying convulsions can occur from abrupt withdrawal. I wouldn't jump onto an article on a subject matter I didn't understand and start stating what is factual and what is not. Are there any doctors who can come on the talk page and just start responding to some of this stuff.--Literaturegeek | T@1k? 13:46, 23 June 2009 (UTC)

The environment has been like this really from the beginning of FA review, have tried dispute resolution, trying to reason with people, compromise, nothing works. It has now escalated as I now have two people with very little knowledge of addiction medicine or medicine in general edit warring with me or bombarding me on the talk page with original research POV stuff.--Literaturegeek | T@1k? 13:48, 23 June 2009 (UTC)

I honestly think like I have always thought that this FA should be closed and abandoned.--Literaturegeek | T@1k? 13:50, 23 June 2009 (UTC)

They have made some helpful comments and edits to the article but it is all canceled out with the above problems whcih paralyse me from improving the article.--Literaturegeek | T@1k? 14:02, 23 June 2009 (UTC)

Issues resolved

Today seemed a bit drama free and was able to find the time addressing the issues raised. I believe that I have resolved the remaining issues of this article. I think that the article is ready for FA promotion now. :)--Literaturegeek | T@1k? 06:57, 24 June 2009 (UTC)