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Benzodiazepine

Nominator(s): Literaturegeek | T@1k? 08:31, 26 May 2009 (UTC)

• Featured article candidates/Benzodiazepine/archive1

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)

• Reference check: Ref #136 (List of Drugs Currently Controlled Under The Misuse of Drugs Legislation) is a dead link. Since its only use it with another ref, removing it may be okay. I am getting any 302 errors where the site requires registration - perhaps a note in the appropriate references noting this would be helpful. Wizardman 20:59, 26 May 2009 (UTC) -

Well spotted. Thank you. Fixed.--Literaturegeek | T@1k? 00:39, 27 May 2009 (UTC)

• Per WP:MSH, there should be no special characters in section headings. SandyGeorgia (Talk) 21:07, 26 May 2009 (UTC)

I don't see any special characters in the headings Sandie. Have they all been removed?--Literaturegeek | T@1k? 00:39, 27 May 2009 (UTC)

I believe this refers to the section "GABA_A receptor activation" which uses a subscript. Cool3 (talk) 16:15, 28 May 2009 (UTC)

Done. I have fixed this problem. Thanks cool3.--Literaturegeek | T@1k? 16:42, 28 May 2009 (UTC)

• Comments I haven't read the article yet, only had a cursory glance, so these are going to be brief:
  • The lead could use a little more structure. Right now, it seems as if you're going for "introduction→history→safety→safety". I'd try something more along the lines of "introduction→history→safety (ADRs and special populations)→misuse and overdose". I'll post a proposed outline later; let me know what you think.

Sounds like an idea FV.--Literaturegeek | T@1k? 00:39, 27 May 2009 (UTC)

• • It would be a great idea to merge the lead image into {{Benzos}}. You could also use an image that shows the common location of side chains, such as File:Benzodiazepine.svg (which also follows the orientation used in most of Misplaced Pages's benzo structures). How do you feel about the example in User:Fvasconcellos/Benzos?

Done. I like it, good idea. I used your example. I hope that you don't mind.--Literaturegeek | T@1k? 00:39, 27 May 2009 (UTC)

• • File:Xanax2mg.jpg has little relevance to the "History" section, and would be better employed elsewhere in the article. How about an image of the structure of chlordiazepoxide, or a photo of Dr. Sternbach?

Done. I have moved the image to drug misuse section. Ya know I have a book which I believe was written by leo Sternbach. Is it ok to photograph and use it?--Literaturegeek | T@1k? 00:39, 27 May 2009 (UTC)

• • The whole "Contraindications, interactions and side effects" section would work better as prose. As a casual reader, I would want a little more context—why shouldn't people with myasthenia gravis take benzodiazepines? (In all likelihood, I don't even know what myasthenia gravis is, let alone why it should be an impediment to using benzodiazepines :) You've provided good context in the interactions section, explaining the interaction as well as noting it; why not do the same for contraindications?

I can do that but it may mean adding a lot of additional refs to explain the contraindications. Leave it with me and I will see what I can do over the next 24 hours.--Literaturegeek | T@1k? 00:39, 27 May 2009 (UTC)

Done. Sections are now a prose.--Literaturegeek | T@1k? 19:45, 27 May 2009 (UTC)

• • "Pregnancy" and "Elderly" could become subsections of a "Use in special populations" section. (You don't have to call it that; it's just a suggestion.)

Done. I liked the name suggestion so stuck with it.--Literaturegeek | T@1k? 00:39, 27 May 2009 (UTC)

• • You discuss the use of benzodiazepines as anticonvulsants, but not as antiepileptic drugs. Although they are rarely used as as such (and quite rightly), you should still explicitly mention this somehow (e.g. "Benzodiazepines are potent anticonvulsants, and are used to treat and suppress seizures due to many causes, such as X, Y, and Z..."). Why only mention their use in status epilepticus? If memory serves, benzos are the first-line treatment for acute seizures in practically all situations, and are instrumental in the supportive treatment of diseases such as meningitis and tetanus. I'm sure you can find references to add this content.

I am not too familar with meningitis but assume you are talking about seizures due to swelling of the brain. I will look into this tomorrow and add relevant citations and date.--Literaturegeek | T@1k? 20:07, 27 May 2009 (UTC)

The article already says that benzodiazepines are used for acute seizures. It also covers there use in tetanus in the other indications section. I could not find a secondary source which mentions benzos for meningitis but I think acute seizures would cover that.--Literaturegeek | T@1k? 20:07, 27 May 2009 (UTC)

• • Hyphenation cleanup on aisle 5 :) Long term effects of benzodiazepines should be Long-term effects of benzodiazepines. "Drug related crime" should be "Drug-related crime".

Done.--Literaturegeek | T@1k? 00:39, 27 May 2009 (UTC)

• • "Legal status" is pretty brief, compared to the rest of the article. No mention of other countries in continental Europe? South America? English-speaking African nations?
• More to come later. Fvasconcellos (t·c) 22:53, 26 May 2009 (UTC)

The legal status section, hmmmm, that is rather tricky. I think that we have a couple of choices, we could either fill the section up with legislation for all the major countries of the world which could create an article in and of itself,,, or we could go the other way and say that "most benzos are classified as Schedule IV controlled drugs but some benzos are classed as Schedule III controlled drugs". Worded better than that of course with some examples eg flunitrazepam, temazepam and midazolam. Drug classification can vary with in individual countries regarding benzos, such as some countries in europe may have temazepam as schedule IV whereas others eg the UK may have it as schedule III. We could end up with a long rambling section. I am leaning towards shortening it and sumarising it, however, if people disagree with me I can try and expand it as best possible. I think that if we want a big section on drug scheduling of all the different countries it should be in benzodiazepine drug misuse article.--Literaturegeek | T@1k? 00:39, 27 May 2009 (UTC)

Ok, Thank you so much guys for your suggestions and feedback. Just goes to show there were more improvements (and still are more improvements probably needed) which I couldn't spot.--Literaturegeek | T@1k? 00:39, 27 May 2009 (UTC)

Sandie, thank you very much for all of the problems that your sharp eye spotted. Your examples helped to show me where else I needed to tidy up. The only thing I was unsure about was you saying that these refs are journals., To me they are webpages. Have I got it wrong?--Literaturegeek | T@1k? 00:48, 27 May 2009 (UTC)

• Comments -
• Current ref 19 (Dr Reg Peart) should be Peart, Reg to match the rest of the refs and needs a last access date.
• Current ref 67 (medicinenet) what makes this a reliable source? Also the link title shouldn't be in all capitals per the MOS
• Current ref 71 (Drummer...) needs a last access date.
• Current ref 77 (Professor Heather Ashton) should be Ashton, Heather to match the rest of the refs. Also needs last access date and publisher.
• Current ref 81 (Dr JG McConnell) Should be McConnel, JG to match the rest of the refs. Also needs a publisher and last access date. What makes this a reliable source?
• Current ref 128 (Government, Australian) Should be Australian Government and needs a last access date.
• Current ref 131 (DEA, USA) should be United States Drug Enforcement Agency and needs a last access date
• Current ref 132 (Blackpool NHS...) needs a last access date
• Current ref 134 (Dutch Government) needs a last access date

Otherwise, sources look okay, links checked out with the link checker tool. Ealdgyth - Talk 14:37, 27 May 2009 (UTC)

Fixed the Reg Peart formating, well Boghog did. Boghog also added the last access date to the Drummer citation. Professor Heather Ashton is not in the article so someone must have changed it to "Ashton H". Medicinenet is a reliable source. They obtain their information from WebMD. I have replaced the McConnell ref with a better citation. There is actually a wiki template field for WebMD. Someone seemed to have fixed the Australian government, Dutch Government and the Blackpool citation problems.--Literaturegeek | T@1k? 20:30, 27 May 2009 (UTC)

Anymore suggestions? Are we getting closer to a successful featured article? :)--Literaturegeek | T@1k? 20:31, 27 May 2009 (UTC)

I have followed up on the improvements suggested by Sandie. I have fixed the accessibilty problems by moving the tables all over to the left hand side. I have also hiphenated words which should have been hiphenated. The Sceptical Chymist has further improved the articles with a number of tweaks and small deletions of redundancy and other improvements. Anything else that needs done to reach featured article status?--Literaturegeek | T@1k? 22:54, 27 May 2009 (UTC)

Paitence. It's normal for FACs to last at least a week. You need to garner a number of supports which will take a bit. (Note that my source check will not result in a support, it's just a check to make sure the basics are covered.) Ealdgyth - Talk 23:29, 27 May 2009 (UTC)

I will try to be patient. Your suggestions even if only covering the basics is still helpful and appreciated and will help get the article a step closer to featured article so I appreciate any suggestions that I get. :)--Literaturegeek | T@1k? 13:17, 28 May 2009 (UTC)

Major progress has been made

Myself, Boghog and Sceptical Chymist and other editors seem to have fixed the problems in the article. Lots of improvements made. Images have now been added. A couple of disputed refs have been replaced with better citations. Any further suggestions and comments are welcome. :) Thanks guys for the help.--Literaturegeek | T@1k? 13:17, 28 May 2009 (UTC)

• Support. A first class piece of work. Congratulations to all concerned. A few minor problems (noted below) but they don't get in the way of FA quality:

• The title of the article is "Benzodiazepine" but the lead begins "The benzodiazepines" with an "s", and the minor discrepancy is jarring. I suggest either rewording the lead so that it starts with the singular form, or renaming the article to the plural form (!), so that the two match. Rewording the lead is probably simpler. It is a small point, but articles should get off on the right foot.... - Done
• For mortality among illicit users I suggest citing Charlson et al. 2009 (PMID 19125401), a recent systematic review, rather than the older primary source Gossop et al. 2002 (PMID 11895269). - Done (fixed by user BogHog).
• In this article, does "anxiety" mean anxiety disorder? If so, I suggest changing the Anxiety wikilinks to Anxiety disorder wikilinks, and using the phrase "anxiety disorder" the first time the subject comes up, with "anxiety" being a shorthand thereafter. That'll be less likely to confuse the general reader. - Disagree.
• Cloos & Ferreira 2009 (PMID 19122540) write that benzos' anxiolytic effectiveness is questioned, and current guidelines don't favor them for anxiety disorders. This doesn't seem to be clearly stated in the article. Done.
• The 2nd "sentence" in Side effects is not a sentence. It could be combined with the 1st sentence. Done (fixed by user Boghog).
• "eg" should be written "e.g.," with periods and a comma. - Done.
• "unbearable symptoms" should be surrounded by double-quotes, not by single-quotes, for consistency with rest of article. - Done (fixed iby user Boghog).
• "5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one substructure (Figure, above right)". What does "above right" mean? Perhaps a relic from an old figure, and the phrase "above right" should be removed now? Also, the chemical name in the text doesn't exactly match the chemical name "5-Phenyl-1,4-benzodiazepin-2(3H)-one" in the figure. Disagree about text not mataching other problem has been fixed. (but I am not a chemist so I could be wrong). Done.
• "syringes & needles" Spell out the "and". Done (fixed by user Boghog).
• The image File:Drogenbeschaffungskriminalitaet 9526.jpg isn't directly related to benzodiazepine; I'd remove it. Disagree.
• I'd remove the See also section, either moving the Z drugs wiklink to the text, or removing it. Done (fixed by user Boghog).
• Some citations are like "Charlson F, Degenhardt L, McLaren J"; others like "Gelder, Michael; Paul Harrison, Philip Cowen". I'd be consistent. The former style seems more popular, so I'd stick with that. Done (fixed by user Boghog).
• Some dates use ISO format ("2009-05-27"), others differing formats ("2009 May 28", "17 December 2008"). Please be consistent. ISO seems to be the most popular in this article and would be fine (I prefer it, though I'm in the minority among Misplaced Pages editors I think). Done (fixed by user Boghog).

Eubulides (talk) 08:23, 30 May 2009 (UTC)

I would be in favour of keeping the image File:Drogenbeschaffungskriminalitaet 9526.jpg. Whilst the image itself may not be directly related to benzodiazepines, neither is for example the pregnancy picture of a baby or the picture of the elderly woman and so on. The image shows property crime which the article states that abuse benzodiazepines are in the mid range for property crime compared to other drugs of abuse. So I feel that the picture is relevant.--Literaturegeek | T@1k? 10:55, 30 May 2009 (UTC)

Actually anxiety is the better word to use because benzodiazepines are most effective in short term acute anxiety, eg acute trauma. Anxiety disorder is a chronic disorder which due to rapid development of tolerance makes benzodiazepines limits their use. So it shouldn't be changed to anxiety disorder if the ref is discussing short term acute anxiety.--Literaturegeek | T@1k? 11:01, 30 May 2009 (UTC)

I don't think that the image having a slightly different chemical name in the picture matters as the caption below the picture clearly states that it is a "skeleton" of many benzodiazepines, so it is clear that it is just the core structure which makes up benzodiazepines. I think that the picture is likely only going to be of interest to those who are interested in the chemistry of benzodiazepines and they will be able to work out what it means. Infact I would consider myself not much more than a layman when it comes to chemistry and molecular structure and I could grasp what it meant by skeleton. However, I am not an expert in chemistry, far from it so if I am wrong then feel free to correct me.--Literaturegeek | T@1k? 12:14, 30 May 2009 (UTC)

Thank you very much Eubulides for your support of the benzodiazepine article going to featured article. Myself and Boghog have fixed most of your suggestions and I have pointed out where I disagreed with a couple of your suggestions above. Thank you for your discription of the article as being first class. A lot of work has went into the article by myself and several other dedicated editors. I would like to thank everyone who has worked on this article, including editors who are only recently enthusiastically trying to get the article to featured article and also reviewers for GA and now FA who have helped point out where improvements should be made. Without this group effort this article wouldn't be of as good a standard as it currently is. I agree with you Eubulides that the article is of featured article standard. Hopefully other reviewers will share your views and support it as a featured article.--Literaturegeek | T@1k? 12:14, 30 May 2009 (UTC)

I have resolved the issue with the chemical structure. I tracked down a peer reviewed source for the basic structure of benzodiazepines and corrected the basic structure given in the text. Boghog I believe updated theimage as well.--Literaturegeek | T@1k? 22:54, 30 May 2009 (UTC)

• Support Comments I think we're there. looking better. Prose can do with some massaging which I am taking care of. I have been correcting some stray commas and removing some repetitive nouns (feel free to re-add any if you feel there is ambiguity upon reading). Journal titles should be unabbreviated and I am doing some as I go as this is an insanely arduous task. Couple of minor issues I will pop below. Casliber (talk · contribs) 10:32, 31 May 2009 (UTC)

Benzodiazepines once bound to the benzodiazepine receptor the benzodiazepine ligand locks the benzodiazepine receptor into a conformation in which it has a much higher affinity for the GABA neurotransmitter. - first word redundant here? Needs some commas maybe.

I am also wondering whether para 3 in the Pregnancy section is a little laboured. This one This can lead to hospitalisation of the pregnant mother, may potentially lead to suicide attempts, and thus potentially the death of the mother and unborn child. maybe lose the last clause as self-evident (?) - also I am wondering whether this sentence too is a bit overdetailed as it talks of two patients in a single study One woman had a medical abortion as she felt that she could no longer cope, and another woman used alcohol in a bid to combat the withdrawal symptoms from benzodiazepines.

Prose looks better Casliber, thanks for your work on it. I fixed the redundancy in the pharmacology section. I have removed those two sentences from the pregnancy section. Thank you for your suggestions and your edits.--Literaturegeek | T@1k? 11:17, 31 May 2009 (UTC)

Great two people supporting and nobody opposing. Looking hopeful that the article will soon be promoted to a featured article. :)--Literaturegeek | T@1k? 14:50, 31 May 2009 (UTC)

Image concern as follows:

Otherwise, all other Images are verifiably in the public domain or appropriately licensed. I hope Túrelio did not smash a car window just for this project... Jappalang (talk) 02:57, 2 June 2009 (UTC)

I have changed the image for the pregnancy section so think that issue is resolved now. I thought similar about the car window! Haha. :)--Literaturegeek | T@1k? 10:05, 2 June 2009 (UTC)

The new image's license was slightly incorrect; the news agency did not retain copyrights, they released it into public domain, unless impossible by law, in which case permission is given for free use. Anyway, I corrected it and no image issues remain. Jappalang (talk) 13:24, 2 June 2009 (UTC)

After a quick glance the article seems good. Some minor comments while I read through it. --Garrondo (talk) 13:45, 2 June 2009 (UTC)

• History: Regarding approval it only says one when it occurred in the US (I suppose it was the first place where it was approved), maybe it could be succintly said if it was followed by the approval in other countries and their date (Europe at least?) - Done.
• In the therapeutic/other uses subsection: I suppose uses commented are only examples of all the possible non-common uses of benzos. This should be stated since as it is pressented now it seems that with this list all possible uses are covered.
• In the contraindications and interactions/contraindications subsection specially the first sentence (The following are some important contraindications or situations where extreme caution should be exercised when prescribing benzodiazepines.), but also most of the subsection sounds to much like directed for phisicians and not for general public. Could it be reworded in some way to avoid this impression? - Done. I think or more work needed?

Are you talking about the metabolism pathways (in the interactions section)? I can remove or change that if you like.

• Although I have not reached the section yet, the picture in the misuse section does not seem very relevant... Even if the description of the image says it is a drug-related theft there is nothing in the picture that points toward it: it is simply a broken glass, and this can occur from multiple causes. I believe the picture is quite uninformative.

I have searched and searched on wiki commons with lots of different keywords and could not find a relevant picture and I am unsure what reviewers would consider relevant. The section says that benzos are associated with property crime and I placed a photo of a car which had been broken into by a drug addict (according to photo discription when you click on it by whoever uploaded it). What type of picture do you think would be relevant? I have changed the text below the picture in the article to say property crime. Thank you for reviewing the article. If you think that it should be deleted even with my change to text below it just say so and I will delete it as I don't want a photo to get in the way of the article going to featured article status.--Literaturegeek | T@1k? 14:52, 2 June 2009 (UTC)

From my point of view it would better be deleted (And I usually agree with loosely connected images, but for me this time is too much...), but it's a debate that fits better in the talk page and with the imput of other editors. It won't interfere in my decision.--Garrondo (talk) 15:40, 2 June 2009 (UTC) - Done. I have deleted the image.--Literaturegeek | T@1k? 00:36, 3 June 2009 (UTC)

• On a second reading of the contraindications: wording sounded quite repetitive. I tried to improve it a bit, but I am not the best one for copy-edits. Maybe somebody better qualified for this task could help with it. - Done.

Just to note that benzos, specifically the first benzo chlordiazepoxide was introduced in pretty much at the same time in all the main countries around the world so I just changed it to 1960 and found a secondary source for it.--Literaturegeek | T@1k? 15:37, 2 June 2009 (UTC)

• Prose comment: Repetition of words lowers the prose quality of the article: just as an example the word withdrawal appears around 40 times in the side-effects section (and there were even more before I copy-edited it a bit), not to talk about the word benzodiazepines. Many of them could be eliminated without problems.--Garrondo (talk) 15:53, 2 June 2009 (UTC) - Done.

I have given it my best shot and was able to remove a lot of the incidences of the word "benzodiazepines" and "withdrawal" when it wasn't needed. I also deleted the disputed image as you are now the 2nd reviewer who didn't think it should remain in the article and I worked on the contraindications section a bit. Any more suggestions or are we on our way to featured article? :)--Literaturegeek | T@1k? 00:36, 3 June 2009 (UTC)

• Comments I fixed a couple of typos, but a few issues still
  • 8000 tons - rest of article is international (mg, ml), this US unit doesn't even have a conversion - Done. deleted.
  • 14,000 patients and 1800 and 8000 tons comma separator or not? - Done. Fixed.
  • Long-term use of benzodiazepines pointless red link unless you are writing the article - Done. Fixed.
  • References. It is better to spell out journal names in full, but even if it's acceptable to abbreviate, shouldn't there be some full stops in, e.g., Int Clin Psychopharmacol (many others)? - In process. This will take time, have made a start

I look forward to supporting soon jimfbleak (talk) 06:47, 3 June 2009 (UTC)

Comment: After rereading the uses section: The thing that benzos can not be used long term due to tolerance and withdrawal and other problems is said at least in two subsections. My proposal is that it is only said in the introductory section and removed from the subsections. I am going to be bold and do it myself. I have also tried to remove redundancies and repetitions. I will have more comments until the end of the week (its a long article and takes quite some time to grab it). Nevertheless it is improving. --Garrondo (talk) 08:19, 3 June 2009 (UTC)

I like your suggestion and change.--Literaturegeek | T@1k? 10:58, 3 June 2009 (UTC)

Comment: First of all I beg pardon for the order in my comments being a bit chaotic, but I put them here as I review the article. Secondly: To have a classification of the drugs in the uses section is very odd, since the classification is only tangentially related to their use. I believe it would be better to create a new "classification" section after history with the introductory sentence and the table of the classification (it would be even better to prosify it if possible).--Garrondo (talk) 08:30, 3 June 2009 (UTC)

Your comments are fine and not out of order to me. The classification based on half life is basically pharmacokinetics so should be below pharmacology. Another editor moved it to the uses section. I will move it back to below pharmacology section unless yourself or another review believes it to be better placed else wherein the article.--Literaturegeek | T@1k? 10:58, 3 June 2009 (UTC)

Comment: Multiple style, grammar and sourcing problems.

• For example, in Benzodiazepine#contraindications I counted four instances of questionable style/grammar per eight sentences: Benzodiazepines should neither be used for chronic psychosis, phobic or obsessional states. ... such as major depression risk of precipitating suicidal tendencies...Prolonged use should be avoided and abrupt withdrawal thereafter...cross tolerant drugs" This sentence Individuals with a history of physical dependence on benzodiazepines or other cross tolerant drugs such as other GABAergic sedative hypnotic drugs including alcohol should generally avoid them as there is a risk of rapid reinstatement of dependency. -- needs some commas.The Sceptical Chymist (talk) 11:10, 3 June 2009 (UTC)

There is nothing wrong with the sourcing and by the way some of your edits were requested to be removed above which I removed or fixed.--Literaturegeek | T@1k? 12:09, 3 June 2009 (UTC)

If it needs a few minor tweaks or comma's why don't you fix it or do you have alterior motives?--Literaturegeek | T@1k? 12:13, 3 June 2009 (UTC)

Also chest pain, changes in heart rate are listed as "less common" side effects. Benzos effect the muscle of the heart and they effect calcium ion channels hence the cardio side effects. The heart if a muscle.--Literaturegeek | T@1k? 12:20, 3 June 2009 (UTC)

My comments were not addressed. The explanations why the text should stay the same were not provided. The Sceptical Chymist (talk) 19:06, 5 June 2009 (UTC)

• I could not find sources that would indicate that (in Benzodiazepine#Side effects) headache, changes in heart rate, chest pain, are significant side effects worth mentioning. The Sceptical Chymist (talk) 11:14, 3 June 2009 (UTC)

Here we go with bold faced lies. You know fine rightly that I provided you with drug company clinical trial data from uptodate.com and I provided you with Roche pharmaceuticals product information leaflet and it was sourced to the "British National Formulary".--Literaturegeek | T@1k? 12:08, 3 June 2009 (UTC)

On the Talk page LG only provided an information leaflet and ref uptodate.com only for one benzodiazepine where the effect in question (headache) was characterized as minor. Considering that there are ~100 BDs on the market, a minor side effect for one of them does not justifies the inclusion of headache, changes in heart rate or chest pain into the overview article. They are just not notable enough.The Sceptical Chymist (talk) 15:44, 3 June 2009 (UTC)

The refs did not say anything about minor. Please don't distort what refs say in order to belittle me. You keep doing it. What is wrong with you? I gave you refs for diazepam and lorazepam and the BNF listed headache for all benzos. I honestly couldn't care if the side effect headache gets deleted, it really isn't a big deal. I am just tired of refs getting distorted and then my editing patterns being put down. I don't mind honest debates over refs.--Literaturegeek | T@1k? 00:22, 4 June 2009 (UTC)

OK, let me repeat what I said in BenzodiazepineTalk.

*I am looking for a description of the class side effects. Ideal source would be a review on BDs from a textbook or from a serious journal (written for specialists not for GPs). I have several textbooks on psychopharmacology in my possession and none of them mentions headache, changes in heart rate and chest pain. (and upset stomach for that matter).

*The formulary presents us with a long and unreadable list of side effects. To make the article readable we have to chose the most notable side effects. WP:MEDMOS also recommends that. I am asking for the additional sources in order to ascertain that the purported side effects are indeed significant and notable. I use Meyer's as a rough guide because it is a comprehensive 5000-pages long handbook on side effects of drugs. It has 14 pages on the side effects of benzodiazepines as a class (in addition to the entries on individual BDs). So if it is not mentioned in Meyer's, in all probability, it is not notable. I am ready to be convinced otherwise with the appropriate citations. The Sceptical Chymist (talk) 02:09, 4 June 2009 (UTC)

Please provide good evidence that The British National Formulary is not a reliable source. Please provide evidence that all doctors in the UK are using unreliable sources for their prescribing practices. The side effect list in this article is not long and unreadable. Please valid reasons for your positions. How many sources would you like? I provided 3? Would you like 10 refs per side effect? 100 refs for the side effect section?--Literaturegeek | T@1k? 02:20, 4 June 2009 (UTC)

BNF is reliable but that does not mean that we should cut and paste random fragments from it. You should only write about notable things. Is it that hard to understand? You did not provide a single appropriate source, because according to your admission, BNF does not give class side effects for BDs. So instead, you used side effects for diazepam and nitrazepam and cut and pasted them. That is not the way to write encyclopedia. On the other hand, I can give you 5-6 psychiatric and psychopharmacology textbooks that do not mention headache, changes in heart rate, chest pain and upset stomach. And, acting in good faith, I could not find a single one mentioning them. The Sceptical Chymist (talk) 02:43, 4 June 2009 (UTC)

I provided ref to uptodate.com which showed them as notable. BNF says they are class effects listing all benzos as "see side effects under diazepam or nitrazepam". BNF is class effects. Probably because a psychiatry book is more interested in certain side effects relevant to psychiatry. This article is should not be written based on side effects relevant to psychiatric practice". They should be general side effects relevant to everyone not just one field of medicine. Please provide citations which show the BNF as an unreliable source. I also provided you with Roche official data sheets as well as uptodate.com. I will be submiting evidence to the admin noticeboard about this sceptical. You trying to ruin this FA with a personal vendetta is not on.--Literaturegeek | T@1k? 05:47, 4 June 2009 (UTC)

Still, you provided no reviews or textbook references even mentioning the above side effects. I insist that they are not notable. The Sceptical Chymist (talk) 19:16, 5 June 2009 (UTC)

The British National Formulary is a testbook is it not? Uptodate.com gives specific percentages of people who have these adverse reactions and says it is within the range of 1%-10% thus notable. You know what I do agree with, that it is more common with IV administration or else elderly after oral administration. Can we agree to maybe add brackets beside the hypotension and say "(more common with IV administration or in the elderly). Here is a citation for the elderly. and you have a citation from a book for IV use. I have provided you. I have already ggiven you the stats of lorazepam from uptodate.com Here is diazepam, also says hypotension, says it for all benzos, but says "Frequency not defined. Adverse reactions may vary by route of administration," thus meaning side effects eg hypotension moore common with IV.--Literaturegeek | T@1k? 09:26, 6 June 2009 (UTC)

My question have not been answered. Let me repeat. I can give you 5-6 psychiatric and psychopharmacology textbooks that do not mention headache, changes in heart rate, chest pain and upset stomach. And, acting in good faith, I could not find a single one mentioning them. Meyler's Side Effects of Drugs a comprehensive 5000-pages long handbook, which has 14 pages on the side effects of benzodiazepines as a class, do not mention these side effects. These side effects are not notable and should be deleted. The Sceptical Chymist (talk) 12:29, 6 June 2009 (UTC)

• This sentence in Benzodiazepines#Paradoxical reactions -- Severe paradoxical reactions such as physical aggression, criminal acts, impulsivity, violence and suicide can occur but are considered rare occurring in less than 1% of the general population. is based on the following sentence in PMID 18922233 abstract: "Physical aggression, rape, impulsive decision-making and violence have been reported, as well as autoaggressiveness and suicide. General population studies indicate a prevalence of these reactions of less than 1%, and meta-analysis has shown that use of benzodiazepines generates aggressiveness more frequently than it reduces it." It is not clear whether the authors mean that benzodiazepines cause these disinhibition side effects in 1% of the patients. Thay may also mean that these traits occur in 1% of the general population but more often in benzodiazepine patients. And so they make a conclusion that benzodiazepines do cause disinhibition. The direct quotations from the full text are needed to resolve this. My question is prompted by the fact that other references point out to 10% frequency of disinhibition -- not 1%. The Sceptical Chymist (talk) 11:33, 3 June 2009 (UTC)

Additionally there seems to be no source or explanation on rationale for the sentence It is possible that oxazepam has a lower rate of disinhibition reactions.--Garrondo (talk) 11:54, 3 June 2009 (UTC) - Done. Removed.

That was Sceptical's edit. I will delete it seeing as someone independent has critisised it.--Literaturegeek | T@1k? 12:14, 3 June 2009 (UTC)

My comment was not answered, the citations were not provided. I will provide the quote indicating that oxazepam may have a lower paradoxical side effects rate than other benzodiazepines. The Sceptical Chymist (talk) 15:41, 3 June 2009 (UTC)

As promised, citations to support inclusion of It is possible that oxazepam has a lower rate of disinhibition reactions. PMID 6133541: "The relationship between other benzodiazepines and hostility has also been studied. Kochansky, Salzman, Shader, Harmatz & Ogeltree(1975), for example, compared chlordiazepoxide and oxazepam. Their findings with chlordiazepoxide supported previous work but they were unable to find an association between increased hostility and the administration of oxazepam... In such patients, chlordiazepoxide and diazepam may release sufficient hostility to result in a 'rage reaction'. To date, no such reaction has been reported with oxazepam, the suggested anxiolytic of choice for these patients." : "Weisman et al (1998) reported that healthy volunteers who had taken diazepam 10 mg were more likely to behave aggressively under low levels of provocation than those who had taken clorazepate, oxazepam or placebo." isbn0-683-30128-4, p. 435: "In two controlled studies, lorazepam was more likely to provoke aggression than oxazepam (103,104)." The Sceptical Chymist (talk) 23:55, 3 June 2009 (UTC)

Please re-insert the sentence you deleted. The Sceptical Chymist (talk) 19:16, 5 June 2009 (UTC)

My comment about Severe paradoxical reactions such as physical aggression, criminal acts, impulsivity, violence and suicide can occur but are considered rare occurring in less than 1% of the general population. was not answered. In addition, the sentence It is possible that oxazepam has a lower rate of disinhibition reactions. was not restored. The Sceptical Chymist (talk) 12:34, 6 June 2009 (UTC)

• Another problematic sentence in Benzodiazepines#Paradoxical reactions Paradoxical reactions may occur in any individual on commencement of therapy but may be more common in certain groups of patients e.g., alcoholics, children and individuals with certain psychiatric disorders. First, use simple language avoid "e.g.". Second, it is based on this sentence in the full text "several predisposing risk factors have been identified. These include young and advanced age, genetic predisposition, alcoholism, and psychiatric and/or personality disorders. Children and elderly patients may be more predisposed than other patients to paradoxical reactions with benzodiazepines." Why are older people not mentioned,? The Sceptical Chymist (talk) 11:43, 3 June 2009 (UTC)

Additionally the word occur appears 4 times in this subsection. Any possible synonyms?--Garrondo (talk) 11:54, 3 June 2009 (UTC)

• A POV problem in Benzodiazepine#Physical dependence and withdrawal. A significant proportion of the doctors (it may even be a majority if you look at the number of prescriptions for alprazolam in the US per year, which is about 100000000) believes that in some situations benefits of continuous prescriptions of BDs overwhelm the risks of dependence and withdrawal. At least one paragraph is necessary reflecting this view.The Sceptical Chymist (talk) 11:51, 3 June 2009 (UTC)

Actually I covered this by mentioning in offlabel use how they are occasionally used long term for panic disorder (off-label indication) and I also even cited evidence for long term effectiveness. See other indications section. Also often patients demand benzos or fail to respond to other medications and doctors turn to them as a last resort and also as they are drugs of dependence this motivates long term use etc. There are lots of reasons, not just one reason for high prescribing levels.--Literaturegeek | T@1k? 12:27, 3 June 2009 (UTC)

Still the fact that many doctors disagree with the NICE guidelines needs to be mentioned to provide the NPOV. The Sceptical Chymist (talk) 15:41, 3 June 2009 (UTC)

Which part are you disagreeing with? The panic disorder is not cited to NICE guidelines or are you talking about nonbenzodiazepines?--Literaturegeek | T@1k? 00:12, 4 June 2009 (UTC)

I suggest including something along these lines (quoted from Kaplan and Saddock's Comprehensive textbook of Psychiatry, 7th edition).

One of the more important areas of benzodiazepine use centers around the discontinuation of effective or ineffective treatment. Pressure to discontinue often arises from the patient, patient's family, or even the medical professional. This is often related to exaggerated fears of becoming addicted or an attitude that use of benzodiazepines is a sign of weakness rather than a treatment for a medical condition. There are some good reasons to discontinue effective pharmacotherapy, including determining if the patient still needs the medication as mentioned above. Others include serious adverse effects or the wish to conceive a child." The Sceptical Chymist (talk) 02:30, 4 June 2009 (UTC) striking a comment, we will address the NPOV after the refs issues are worked out The Sceptical Chymist (talk) 12:37, 6 June 2009 (UTC)

• More to follow... The Sceptical Chymist (talk) 11:52, 3 June 2009 (UTC)

Sceptical I really do not trust your motives here. On the talk page you were arguing that other reviews say 10% for paradoxical reactions. Now you are arguing that really the ref wasn't talking about adverse reactions to benzos (despite the title of the review article) but were talking about the general population which is ludicrous. I really couldn't be bothered getting into lengthy debates with you as I have dealt with editors like you before (mwalla, scuro) and I can see a pattern emerging. Ironically I helped get mwalla who was stalking and harrassing you banned, although they were harassing me to. You have been cutting words out of sentences on main talk page, quoting refs out of context and starting pointless debates. I think that for some reason this has become personal and you want to sabotage this featured article review, hence you denouncing the article as "poorly sourced" (when it is 95% secondary sources). Ya know this is not about article content is it? This is personal isn't it? To be quite honest I would just delete all of the side effects, contraindications sections and be done with it but as this is personal it won't matter. I am not saying you don't have some good points, but it is mixed in with disruptive behaviour.

Anyway maybe you will succeed in destroying any chance of this going to featured article and I bet that will make you proud.--Literaturegeek | T@1k? 12:08, 3 June 2009 (UTC)

Ok, I have lost my cool. I striked out my comments. I am sorry to everyone for losing my cool. I will seek out the help of an administrator rather than losing my cool in future. Thank you.--Literaturegeek | T@1k? 13:21, 3 June 2009 (UTC)

There are enough administrators watching this page, and Cas is an ArbCom member. Please note that, in principle, I do not oppose this article. It just needs a thorough clean-up, reference check and, possibly, some strategic deletions before I support it. The Sceptical Chymist (talk) 16:58, 3 June 2009 (UTC)

• One more comment on paradoxical reactions: I feel the sentence Disinhibition often happens when benzodiazepines are taken by individuals who have a borderline personality disorder or consumed with alcohol or in high doses is absolutely redundant. The first part (borderline personality) is a subcase of the precceding sentence (psychiatric disorders); alcohol is also in the precceding sentence, while the last part (high doses) is included in the next sentence. I propose to simply eliminate the sentence. Bests to everybody; and please remain civil.--Garrondo (talk) 13:51, 3 June 2009 (UTC)

I am fine with that edit removing redundnacy, no need to have it mentioned twice. At some point previously the section mentioned that up to 58% of individuals with borderline personality disorder experience a disinhibiting reaction from benzos. That statistic is so high making that side effect almost typical and BDP is not a rare psychiatric disorder that I feel that it should be mentioned. What do you think?--Literaturegeek | T@1k? 14:58, 3 June 2009 (UTC)

My suggestion to include elderly into the list of the people prone to the parodoxical reactions was not addressed. The Sceptical Chymist (talk) 15:41, 3 June 2009 (UTC)-Done---Garrondo (talk) 15:51, 3 June 2009 (UTC)

Eliminated second part of the sentence and added elderly.--Garrondo (talk) 15:45, 3 June 2009 (UTC)

• Comment. The following information in Benzodiazepine#withdrawal is outdated. It is not known definitively whether such symptoms persisting long after withdrawal are related to true pharmacological withdrawal or whether they are due to neuronal damage as result of chronic use or withdrawal.(based on PMID 1675688). The article was written in 1991. Since then, it has become much clearer that prolonged withdrawal syndromes are not caused by "neuronal damage". They are caused by increased expression of non-functional GABAa receptors. (see PMID 11812247) The Sceptical Chymist (talk) 01:34, 4 June 2009 (UTC)

That ref is not about protracted withdrawal or persisting symptoms after withdrawal depending on however you define it.--Literaturegeek | T@1k? 01:39, 4 June 2009 (UTC)

PMID 11812247 is about withdrawal symptoms from prolonged BD use: "Our working hypothesis is that tolerance to the effects of chronic treatment with benzodiazepines is associated with the expression of aberrant GABAA receptors in the mammalian brain. Likewise, withdrawal phenomena manifest when inappropriate GABAA receptors have to function in the absence of drug following abrupt cessation of treatment.". On the other hand Ashton (PMID 1675688) simply speculates about "neuronal damage". This speculation has not been supported by the subsequent research. I searched PubMed for (benzodiazepine withdrawal "neuronal damage") and found no other articles supporting this speculation. The Sceptical Chymist (talk) 01:50, 4 June 2009 (UTC)

Correct the ref is on withdrawal symptoms from prolonged use. But to repeat, the ref is not about protracted withdrawal. Please stop disrupting this review process. Thank you.--Literaturegeek | T@1k? 01:57, 4 June 2009 (UTC)

OK. Let me repeat, too. Ashton is an outdated speculation. No serious researcher since then suggested that BDs may cause "neuronal damage". The burden of proof is on you, according to WP:V. The Sceptical Chymist (talk) 02:19, 4 June 2009 (UTC)

High dose abusers of benzodiazepines have shown enlarged cerebrospinal fluid spaces with associated brain shrinkage. Neuropsychological function can be permanently affected in chronic high dose abusers of benzodiazepines, with brain damage similar to alcoholic brain damage, as was shown in a 4 to 6 year follow-up study of benzodiazepine abusers by Borg and others of the Karolinska Institute. The CT scan abnormalities showed dilatation of the ventricular system. However, unlike alcoholics, sedative hypnotic abusers showed no evidence of widened cortical sulci. The study concluded that, when cerebral disorder is diagnosed in sedative hypnotic benzodiazepine abusers, it is often permanent. An earlier study by Borg et al. found evidence of cerebral disorder in those that exclusively abused benzodiazepines, suggesting that cerebral disorder was not the result of other substances of abuse. Withdrawal from high dose abuse of nitrazepam have caused severe hypoperfusion of the whole brain with diffuse slow activity on EEG. After withdrawal, abnormalities in hypofrontal brain wave patterns persist beyond the withdrawal syndrome which suggested organic brain damage occurs from chronic high dose abuse of benzodiazepines. Some studies have demonstrated brain damage in therapeutic dose users whereas other studies have refuted that benzodiazepines caused structural brain damage. The evidence seems to suggest some form of brain damage but whether the long term effects of benzodiazepines are due to structural brain damage or functional brain damage remains to be determined conclusively. Two publications have suggested that lorazepam is more toxic than diazepam. Permanent brain damage may result from chronic use of benzodiazepines similar to alcohol related brain damage. The brain damage reported is similar to but less severe than that seen in chronic alcoholics. Brain damage reportedly appeared to be dose dependent with low dose users having less brain shrinkage than higher dose users. However, two studies found no evidence of brain shrinkage in prescribed benzodiazepine users.

Professor Ashton a leading expert on benzodiazepines, from Newcastle University Institute of Neuroscience, has been cautious in jumping to any firm conclusions and is an advocate for further research into long lasting or possibly permanent symptoms of long term use of benzodiazepines. She has stated that she believes that the most likely explanation for lasting symptoms is persisting but slowly resolving functional changes at the GABA_A benzodiazepine receptor level. Newer and more detailed brain scanning technologies such as PET scans and MRI scans have never been used to investigate the question of whether benzodiazepines cause functional or structural brain damage. Professor Ashton tried to acquire funding to perform scans using more detailed scanning technologies such as PET scans and MRI scans but was turned down for research funding. At present the question of whether benzodiazepines cause structural or functional brain damage remains unanswered definitively.

Sceptical this is not how things work. You are basically saying "My opinion says this" and you HAVE TO disprove what I said.. You need to provide citations to back up what you said.--Literaturegeek | T@1k? 02:41, 4 June 2009 (UTC)

Please provide evidence for your statement that "Ashton is outdated". She is still actively publishing by the way.--Literaturegeek | T@1k? 02:43, 4 June 2009 (UTC)

No what I am saying is that you have to prove that the newer review PMID 11812247 on the neurophysiology of withdrawal syndrome with BDs is incorrect. You seem to be doing good. So, why do not you replace the Ashton speculations with the real references you gave above and fit it in a couple of sentences. I, on my side will give a short summary of biopsychopharmacological view. And we will say that this is controversial topic. One caveat, though, you cannot use references on abusers since the withdrawal paragraph discusses the withdrawal from normal therapeutic use. Or you have to specify that certain references are related to abusers and do not mix them with those that are related to a brain shrinkage from therapeutic use of BDs. The Sceptical Chymist (talk) 03:03, 4 June 2009 (UTC)

I see, so I have to show (actually prove) that an irrelevant ref which is not about protracted withdrawal is not relevant to challenging protracted withdrawal statement. I don't think that I like that idea, it is very time consuming. At least you think that I am doing a good job at this. The reason skeptical is this. The refs above are primary studies, as this is going to FA I would rather stick with the review paper by Ashton. Thank you. Some of refs above were on therapeutic, some on abusers. I have no intention on adding them to the article.--Literaturegeek | T@1k? 06:30, 4 June 2009 (UTC)

Another problem with Ashton ref that it is not a review, rather it is a summation of her experience of work in the field of BD dependence. For example, she does not give any supporting quotations for her neural damage hypothesis. I doubt if that is really an appropriate secondary source. The Sceptical Chymist (talk) 19:16, 5 June 2009 (UTC)

Yes in your opinion but pubmed and the journal it was published in disagree and have designated it a review article and thus is a secondary source. I posted info above from other sources regarding brain damage and neuronal toxicicity.--Literaturegeek | T@1k? 09:33, 6 June 2009 (UTC)

To recap, we are talking about two Ashton references. Both are used to support dubious sentences. One is that withdrawal from BDs may be pleasant. Another dubious sentence is that BDs may cause brain damage.

First Ashton ref is a website "howto", which has not been peer-reviewed, see ]. Second Ashton ref (Ashton, 1991) is a peer-reviewed article ]. However, according to WP:MEDRS it is of the lowest evidence class -- Class IV Evidence from expert committee reports or opinions and/or clinical experience of respected authorities. According to WP policies, extraordinary claims require extraordinary support. These claims are supported only by the weakest evidence and should be deleted. The Sceptical Chymist (talk) 13:03, 6 June 2009 (UTC)

More comments

• As I read through the article I feel it is not as well written as I first thought regarding prose: there are multiple repetitions of content, structures or words. I will try to fix some of those as I read through the whole article, but may take time, but at the moment I feel is not enough to become a FA. Until now I think I have fixed all sections before pregnancy.--Garrondo (talk) 13:29, 4 June 2009 (UTC)
• 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 (Contraindications, special populations and pharmacology).--Garrondo (talk) 13:29, 4 June 2009 (UTC)
• Pharmacocinetiks section should be prosified instead of using a table.--Garrondo (talk) 13:29, 4 June 2009 (UTC)
• Reading use in the elderly says: Long term use of benzodiazepines in the elderly can induce a pharmacological syndrome which includes a wide range of physiological and neuropsychological symptoms which can be mistaken for the effects of old age however going to the ref abstract we find:Behavioral findings include symptoms such as drowsiness, ataxia, fatigue, confusion, weakness, dizziness, vertigo, syncope, reversible dementia, depression, impairment of intellectual, psychomotor and sexual function, agitation, auditory and visual hallucinations, paranoid ideation, panic, delirium, depersonalization, sleepwalking, aggressivity, orthostatic hypotension, and insomnia. I know the abstract compares benzodiazepines use and old age, but the truth is that symptoms commented in the abstract are not typical from normal aging but of dementia problems. It is my impression, but I feel this is not the best reference: low quality journal, quite old... --Garrondo (talk) 13:45, 4 June 2009 (UTC)
• Simplification proposal: The following paragraph ---A large cohort study found that benzodiazepine use is associated with a significantly higher incidence of hip fracture. Benzodiazepines of a short half-life are as likely to be associated with hip fracture as long-acting ones. Because hip fractures are a frequent cause of disability and death in the elderly, efforts have been underway to reduce benzodiazepine prescribing in the elderly. A review of the literature from between 1975 and 2005 found that medical papers consistently report increased risk of falls and fractures in the elderly. Benzodiazepine hypnotics produce also the most significant effects on body sway. Newer hypnotics (e.g., zaleplon and zolpidem) do not seem to cause such profound adverse effects on the elderly. Still, a law introduced in New York State reducing benzodiazepine use by 60% did not result in a measurable decrease in hip fractures. This suggests that any effect of benzodiazepines on fracture rate may be non-significant and more important factors predict fracture rate such as osteoporosis rather than benzodiazepine induced falls. Use of other psychotropic drugs which are often prescribed in combination with benzodiazepines particularly SSRI antidepressants may also effect fracture rate--- is from my point of view repetitive, long, goes to too specific details and goes far from the point at some moments. I propose to change it by something simpler such as: Medical literature points to benzodiazepines, independently of their halve-lifes, being associated with falls and specifically hip fractures in the elderly. Because hip fractures are a frequent cause of disability and death in the elderly, efforts have been underway to reduce benzodiazepine prescribing. Still, a law introduced in New York State reducing benzodiazepine use by 60% did not result in a measurable decrease in fractures. This suggests that other factors could better predict them.
• Lolk 2006 article is in danish: I am sure there are plenty of reviews on benzos in elderly in english
• There were MANY MANY REPETITIONS in the elderly section: I have changed it completely. If anybody does not agree lets discuss it in talk page.--Garrondo (talk) 14:24, 4 June 2009 (UTC)

Great job. But somehow in the flurry of the recent edits, the introductory sentence to the Withdrawal part got incomprehensible. How about starting it with: "Discontinuation of benzodiazepines, even after a relatively short course of treatment (3–4 weeks), may result in a withdrawal syndrome." It seems to me that separation of introduction, symptoms and management of withdrawal syndrome is artificial and unnecessary. For example, introduction talks about symptoms without saying what they are. The Sceptical Chymist (talk) 23:06, 4 June 2009 (UTC) Done:--Garrondo (talk) 07:35, 5 June 2009 (UTC)

• Comments. Long lists of side effects in Benzodiazepine#withdrawal syndrome and Benzodiazepine#Pregnancy are both useless and unreadable. I believe that only 2-5 of the most important or troubling symptoms should remain, and maybe some explanation should be added to them. We should follow the good advice from WP:MEDMOS#Drugs: "Try to avoid cloning drug formularies such as the BNF and online resources like RxList and Drugs.com. Extract the pertinent information rather than just dumping low-level facts in a big list. For example, a long list of side effects is largely useless without some idea of which are common or serious." The Sceptical Chymist (talk) 23:18, 4 June 2009 (UTC)

Disagree, there at least a good 40 - 50 common symptoms and another 40 - 50 less common ones, the list is shortened. I think that you are taking the guideline statement of avoiding "long lists" to the extreme. The symptoms listed are within MEDMOS guidelines.--Literaturegeek | T@1k? 15:57, 5 June 2009 (UTC)

That still leaves cloning the formulary and just dumping low-level facts.The Sceptical Chymist (talk) 19:06, 5 June 2009 (UTC)

• Having some statistical data would make the article more comprehensive. What % of population use them? How much of them chronically? What % of the population abuses them? What is the number of prescriptions for the most popular benzodiazepines? The Sceptical Chymist (talk) 23:37, 4 June 2009 (UTC)

I believe that I can achieve approximate figures for this but may need to use a primary source. Personally I would rather avoid adding this kind of data as it means using primary sources (who knows though I may find a review paper with the stats).--Literaturegeek | T@1k? 15:57, 5 June 2009 (UTC)

You should be able to find such secondary sources. In any case, no guideline should stand in the way of improving an article, see WP:Ignore. Also see above Eubulides example with a rare disease. If you are not able to find newer secondary studies his reasoning abour rare diseases would apply here and even from his point using primary sourced would be permissible. Besides, WP:V policy supports judricious use of primaty sources. The Sceptical Chymist (talk) 19:06, 5 June 2009 (UTC)

• This fragment from Benzodiazepine#Withdrawal sounds biased and unscientific: Withdrawal from chronic use is usually beneficial due to improved health such as cognition and functioning with possible benefits in employment status. In fact, some people feel better and more clear-headed as the dose gradually gets lower, so withdrawal from benzodiazepines is not necessarily an unpleasant event. It also contradicts the bulk of the data in the chapter. The best is probably to delete it. The Sceptical Chymist (talk) 23:48, 4 June 2009 (UTC) Done

This statement was actually added to remove bias from the article originally, to remove the "doom and gloom" of the withdrawal process. What is the contradiction? Do you have a source which states that remaining on benzos improves or does not effect employment status?--Literaturegeek | T@1k? 15:57, 5 June 2009 (UTC)

No, but I have sources talking about how great people feel when they start taking BDs. Imagine that I put such a testimony there. Would that be scientific or encyclopedic? The Sceptical Chymist (talk) 19:06, 5 June 2009 (UTC)

It wouldn't be relevant because that section is oon tolerance and dependence not on short term use (people starting them). I know and agree that people like benzos when they start them, that is partly due to their abuse potential or else due to their therapeutic effectiveness. Actually the article already covers this. The article talks about the effectiveness of benzodiazepines in the short term.--Literaturegeek | T@1k? 10:07, 6 June 2009 (UTC)

This answer is evasive. The sentence is unencyclopedic extraordinary claim and based on a weak evidence - Ashton's website howto . The Sceptical Chymist (talk) 13:10, 6 June 2009 (UTC)

I was not trying to be evasive. Just delete that sentence. Like I said it was added in order to bring neutrality after an editor complained the withdrawal section was all "doom and gloom". That was how that ended up there so I tried to show some "positives" rather than all "negatives" of withdrawal. Prof Ashton does not own that website, it just hosts one of her manuals with her permission I believe. I can find a large number of sources about cognition and other effects improving with abstinence from benzos if you like. It is not extraordinary.--Literaturegeek | T@1k? 13:17, 6 June 2009 (UTC

• This sentence from the same chapter -- Effects of other cross tolerant sedative hypnotics, such as barbiturates or alcohol are additive and thus also contribute to severity. -- is not supported by the reference, at least by the abstract (PMID 7841856). The abstract states that "Dependence on alcohol or other sedatives may increase the risk of benzodiazepine dependence" but nothing is said about the increased severity. The Sceptical Chymist (talk) 23:58, 4 June 2009 (UTC) Addressed.

Thank you for identifying this problem, I have reworded the sentence.--Literaturegeek | T@1k? 15:57, 5 June 2009 (UTC)

• Pregnancy chapter. International statistics show that 3.5% of women consume psychotropic drugs during pregnancy and of that 3.5% up to 85% report using benzodiazepines (PMID 7908878). This is based on a 1990 study. Nowadays use of BDs is much lower. Newer ref is needed. The Sceptical Chymist (talk) 01:36, 5 June 2009 (UTC)

I wouldn't say much lower. The prescribing levels only had a big fall in the 1980's then sort of stabalised, then a small fall as the Z drugs took over at least in the UK. I am not aware of any yearly stats being done on use of benzos during pregnancy so more uptodate stats that you are looking for may not be available. I have added 1990 to the article text. I am on the fence of whether to remove the stats or not but leaning towards keeping them. On the one hand they provide useful statistical data for the reader and removal takes away from the article I think but on the other hand like you say they are old stats. I wonder could other reviewers weigh in on this?--Literaturegeek | T@1k? 10:07, 6 June 2009 (UTC)

It is much lower than your numbers, at least in the US. I remember reading that somewhere. You should be able to find a relevant reference. If you cannot, you should remove the statistics. The Sceptical Chymist (talk) 19:06, 5 June 2009 (UTC)

Done. Ok, I have removed the statistics as they are almost 20 years old and disputed. I could not locate any more recent statistics. I remember when writing the article spending a lot of time looking for more recent stats but could not find them for pregnancy.--Literaturegeek | T@1k? 10:07, 6 June 2009 (UTC)

• Pregnancy chapter. In the United States, the Food and Drug Administration has categorized benzodiazepines into either category D or X meaning potential for harm in the unborn has been demonstrated. This is based on an unreliable reference -- a website of a psychiatric practice BJCHelathcare. Moreover, it misrepresents this reference. The website says: "Benzodiazepines generally carry FDA ratings of "X- contraindicated in pregnancy" or "D-positive evidence of risk." For example, clonazepam is in category "C". The Sceptical Chymist (talk) 01:45, 5 June 2009 (UTC) Addressed

You are incorrect, clonazepam is category D. See comments below.--Literaturegeek | T@1k? 15:57, 5 June 2009 (UTC)

• Pregnancy chapter. ... possible but uncertain effects of benzodiazepine use to the fetus include, abortion, malformation, intrauterine growth retardation, functional deficits, carcinogenesis and mutagenesis. This sentence is taken from the introduction to PMID 11773648, where the authors list all the possible effects of BDs on fetus. In the body of the paper, the authors rule out most of these side effects to conclude that "In view of the available literature, it appears to be safe to take diazepam during pregnancy. However, use of diazepam during lactation is not recommended because it has the potential to cause lethargy, sedation, and weight loss in infants. The use of chlordiazepoxide during both pregnancy and lactation seems to be safe. Few data are available to justify avoiding the use of clonazepam during pregnancy or lactation. No adverse effects have been reported with the use of lorazepam during lactation. However, it would be prudent to avoid alprazolam during both pregnancy and lactation." Thus, the reference is misrepresented. Independently, it is well known that BDs are not carcinogens (see American Journal of Epidemiology Vol. 141, No. 12: 1153-1160). The Sceptical Chymist (talk) 02:35, 5 June 2009 (UTC)

I will need to reread the ref. The section does say that chlordiazepoxide and diazepam have a better safety profile than other benzodiazepines so I am not sure if what you say is correct. But like I say I will need to reread the ref. Are they talking about taking benzos throughout pregnancy or short courses etc?--Literaturegeek | T@1k? 15:57, 5 June 2009 (UTC)

Benzos have no carcinogenic potential? Of all studies addressing that issue are very limited in humans but of the studies several have shown carccinogenic potentials and others have not so at best it is controversial. In animals benzos are carcinogenic and this is accepted and is in the prescriber data sheets for most if not all benzos. I can provide you manufacturer data sheets for this if you like. There are hundreds of refs on animal carcinogenicity and benzos. Oh I know that epidemiology paper you are talking about. That is only a primary study of only 2,000 or something random patients with cancer trying to disprove benzos are carcinogenic. Seeing as only probably 1-2% of the general public are long term users of benzos they probably only had maybe 10-20 patients who were actually using benzos so study is not "proof", I doubt that it discounts the study which assessed 1.1 million American citizens which found increased cancer levels and death even after controlling for other possible causes. It is cited in the long term effect of benzodiazepines article for neutrality. It is rare that a single smallish primary study can be classed as definitive and a single primary small primary study (small because of the nature of the problem they were trying to identify) does not mean "well known". You need more than a primary study to say "well known".--Literaturegeek | T@1k? 16:12, 5 June 2009 (UTC)

Please address my question. The Sceptical Chymist (talk) 19:06, 5 June 2009 (UTC)

I tried to Sceptical as best that I could but explained that I would need to read the ref as I do not know it off by heart. Then I can address your question.--Literaturegeek | T@1k? 19:42, 5 June 2009 (UTC)

See WP:MEDMOS where it states that primary sources should not be used to debunk secondary sources.--Literaturegeek | T@1k? 16:30, 5 June 2009 (UTC)

There are probably well over a 100 common or occasional notible withdrawal symptoms. This article is not a "laundry list" of withdrawal symptoms as only a dozen or so are listed. The feeling more clear headed was actually added to make the section more neutral as without it it makes withdrawal sound like a nightmare as a previous version was. ref is not misrepresented. Clonazepam is category D. No benzo is category C. You are confusing the Australian categorisation system which is different. I will respond more later.--Literaturegeek | T@1k? 14:01, 5 June 2009 (UTC)

You data are correct but they are from primary source, therefore you are wrong. You are correct about category D for clonazepam. But I took Category C from a review. So you are trying to disprove a review with a primary source - a datasheet. Therefore I am right. You see where the heavy and uncritical preference for "secondary sources" leads you.:) The Sceptical Chymist (talk) 19:06, 5 June 2009 (UTC)

No I am not, it is just the official classification that the United States drug regulatory bodies assigned to it so review versus primary sources doesn't come into it. Actually I have read a number of sources, data sheets, FDA over my time with benzos that drug categorisation is category D. You must be using Australian review article then or similar.--Literaturegeek | T@1k? 19:45, 5 June 2009 (UTC)

I was being sarcastic. I am sorry. You are absolutely correct about D for clonazepam, and the review I used was wrong. I suggest not to concentrate on whether the source is secondary or primary. Let's concentrate on which source is reliable and improves the article. This leaves the issue with the source you used, which is unreliable. Plus the wording even in that source implies that some benzodiazepines are in category C. You have to find a better source. The Sceptical Chymist (talk) 20:36, 5 June 2009 (UTC)

Oh, I missed the joke, funny as it was. :) I am sure we can find a reliable source for that to replace the unreliable one. I am still on a semi wiki break as you may be aware if following my userpage but will get to work on it and other issues soon.--Literaturegeek | T@1k? 20:47, 5 June 2009 (UTC)

I have replaced the citation for pregnancy category with a better citation. So this issue is Done.--Literaturegeek | T@1k? 10:07, 6 June 2009 (UTC)

Not Done. This is certainly an unintentional confusion but the wording and the reference seem to have remained the same. The Sceptical Chymist (talk) 14:08, 6 June 2009 (UTC)

Arbitrary break 1

Notes

• Please see my edit summaries for some MoS issues that need review.
• Some of the prose issues raised above are still present, example:
  • ... Caution is required in individuals with ... elderly and debilitated, ...
• The section, "Contraindications and interactions" is followed by "Contraindications" and "Interactions" (see WP:MSH, also WP:MEDMOS).
• Some of the comments (above) are unsigned, so it's hard to see where things stand, but I still see issues that appear unaddressed. I would not like to restart this FAC, but it's unclear what is addressed and what isn't at this point. SandyGeorgia (Talk) 15:41, 5 June 2009 (UTC)

• I have installed several changes that I think addressed all the topics raised by the edit summaries mentioned in the first bullet of SandyGeorgia's comment. Eubulides (talk) 03:02, 6 June 2009 (UTC)

Further comments

• Pregnancy chapter. The last paragraph starting Discontinuing benzodiazepines abruptly has a high risk of causing serious complications... is based on PMID 11212593. This reference is irrelevant and the paragraph should be deleted. Out of 44 pregnant women described, the majority (25) was taking antidepressants and only 2 were taking exclusively benzodiazepines. The reference to a significant degree is on antidepressant withdrawal. The Sceptical Chymist (talk) 22:32, 5 June 2009 (UTC)

I need to read that ref. Were there women who were on both benzos and antidepressants? What was the number? It would be a shame if the section was deleted because I thought that it was important info as without it preegnant women could do more harm than good cold turkeying benzos or antidepressants, i.e. killing the baby via spontaneous abortions or putting themselves in a suicidal state just to avoid a 1 in 5,000. Perhaps we could reword it to reduce undue weight, dunno man will reread the ref. Thank you for raising this problem though.--Literaturegeek | T@1k? 01:09, 6 June 2009 (UTC)

• Elderly chapter. Benzodiazepines are generally not recommended for the elderly due to a range of adverse effects. -- Not in the references cited. The Sceptical Chymist (talk) 22:50, 5 June 2009 (UTC)

Yea, it said risk/benefit ratio is lowest for elderly or words to that effect. A bit "originnal researchy" to jump to say not recommended. I have reworded the sentence. Although here is a ref which says that benzos should in general be avoided in the elderly.--Literaturegeek | T@1k? 01:09, 6 June 2009 (UTC)

• Elderly chapter. The toxicity is increased with the coadministration of other central nervous system depressants or from long term use of benzodiazepines. -- Not needed. There is a similar sentence in Interactions. The Sceptical Chymist (talk) 22:50, 5 June 2009 (UTC)

Ok fair enough, we could remove that bit.--Literaturegeek | T@1k? 01:09, 6 June 2009 (UTC)

• Elderly chapter. The elderly are at an increased risk of dependence... etc to the end of the paragraph. -- Unsupported by any citations. The Sceptical Chymist (talk) 23:16, 5 June 2009 (UTC) Fixed. Someone split a paragraph and moved the sentence to the bottom of the section leaving several sentences uncited.--Literaturegeek | T@1k? 12:50, 6 June 2009 (UTC)

It is supported but the citation seems too have been deleted? I can't see it at the end of the paragraph. It was cited not too long ago.--Literaturegeek | T@1k? 01:09, 6 June 2009 (UTC)

• Elderly chapter. Benzodiazepines are one of the most common causes of drug induced dementia affecting up to 10 percent of patients attending memory clinics. A past history of benzodiazepine use and withdrawal may also predict dementia but the literature is conflicting and inconclusive. -- Dubious. While the older reference PMID 7873091 does implicate BDs in dementia, the 10% number is for all the cases of drug-induced dementia not only for related to BDs. The later analysis PMID 15841867 is misrepresented. Nowhere it says that BDs use may predict dementia, only that the results are conflicting : "Six papers met the inclusion criteria. Two studies reported a lower risk of cognitive decline in former or ever users, two found no association whatever the category of user, and three found an increased risk of cognitive decline in benzodiazepine users." Since the long-term use of BDs is a risk factor of dementia, I suggest re-writing and re-referencing. The Sceptical Chymist (talk) 23:53, 5 June 2009 (UTC)

Agreed, the other common drugs need added, I have added them.antihypertensives and anticholinergic. I "think" but can't be sure that I did add in these other drugs but they were deleted by someone as not being relevant to the article (but could be wrong).--Literaturegeek | T@1k? 01:09, 6 June 2009 (UTC)

I don't think that ref pmid15841867 is misrepresented because it is summarised as being "conflicting" (meaning papers exist saying the opposite of each other). It reports on studies as you pointed out finding an association with benzos and cognitive decline and dementia and it reports of studies which found opposite so the word "may" is appropriate being clarified with statting in article that the results are conclicting and inconclusive. If the article used the word "does" instead of "may" then that would be misrepresenting but it isn't summarised that way. perhaps I am misinterpreting you or if not does what I say make sense?--Literaturegeek | T@1k? 01:09, 6 June 2009 (UTC)

• Elderly chapter. The whole paragraph starting Regarding phsyical traumas medical literature points... fails the reference check. Neither of the references provided (at least from the abstracts) supports any of the information in the paragraph. The Sceptical Chymist (talk) 00:00, 6 June 2009 (UTC)

Since I was last editing significantly here the refs seem to be deleted. The wording of that sentence I think also has been changed but could be wrong. All of that used to be referenced again. I also believe that reviews haave been deleted and replaced with a single primary study. It was definitely cited to review articles only a week or so ago. Dunno who deleted it as I have not checked edit history and trying to address all points before going to bed.--Literaturegeek | T@1k? 01:29, 6 June 2009 (UTC)

• Elderly chapter. The last paragraph. Suggest moving The success of gradual-tapering benzodiazepines is as great in the elderly as in younger people to Withdrawal chapter. Suggest deleting Benzodiazepines should be prescribed to the elderly only with caution and only for a short period at low doses as it repeats the recommendations for everybody else. The Sceptical Chymist (talk) 00:18, 6 June 2009 (UTC)

I would support the moving off the gradual tapering info over to the withdrawal section. I would prefer that the low doses and caution stays in the elderly section because other sections don't talk about the lowest possible dose except for I think the pregnancy section and the hypnotic section so those recommendations are not in the article for everybody else and every prescribing indication.--Literaturegeek | T@1k? 01:29, 6 June 2009 (UTC)

• Most of the Elderly chapter is a repetition of the earlier information. I suggest deleting it and inserting a paragraph about the elderly into the Side effects chapter. This paragraph would state two things: "Side effects of BDs in elderly are often more pronounced and they should be used with caution. A long-term BD use is one of the risk factors for dementia." The Sceptical Chymist (talk) 00:18, 6 June 2009 (UTC)

I disagree, the elderly is such a large group of patients and respond differently to benzodiazepines. I believe that it is a notible enough to have a section. I think that the section should stay.--Literaturegeek | T@1k? 01:29, 6 June 2009 (UTC)

Can I request that when doing bulk deletions that people be more cautious and not to delete review articles which results in leaving facts uncited as this will make the featured article much more difficult aand prolonged if we need to keep retrieving refs for the then uncited data left.--Literaturegeek | T@1k? 01:29, 6 June 2009 (UTC)

I think that this edit was over-enthusiastic or done to hastily which lead to a lot of content being left uncited or looking like refs were misrepresented in the elderly section.--Literaturegeek | T@1k? 02:01, 6 June 2009 (UTC)

I disagree with this edit garrondo, I feel that whilst being a good shortening of the section it went overboard and some important facts were left uncited as well as some productive content for the reader was removed which had a negative effect on the article. Now those wanting information on the elderly are essentially going to get B rated content at best rather than featured article content for the over 65's. Can we discuss?--Literaturegeek | T@1k? 02:08, 6 June 2009 (UTC)

Article is being made worse

Someone has made several sentences uncited, by moving text around without moving citations along with the sentences or else doing careless bold deletions. This is making things look like refs are misrepresented and elderly section uncited. I do not want to haave to rewrite the whole article I noticed this happening in the elderly section and withdrawal section. If this continues we are going to end up a B class article. I fixed hopefully all of these issues. Please stop who ever is doing this.. Always make sure you know how text is cited before moving it around or deleting it.--Literaturegeek | T@1k? 12:50, 6 June 2009 (UTC)

Do not panic. I do not hold that against you. It probably was Garrondo. He did an admirable re-writing but may have lost a few refs. Just restore the refs without reverting to the older text. The Sceptical Chymist (talk) 13:32, 6 June 2009 (UTC)

This FAC needs to be restarted for a fresh look; there do appear to be legitimate issues that may still need to be addressed. After the restart, pls try to keep comments brief and focused on Wp:WIAFA. It may be helpful to take lengthy discussions to the talk page, and summarize the objection per WIAFA to the FAC. SandyGeorgia (Talk) 19:18, 6 June 2009 (UTC)

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