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{{Backwardscopyvio | url = https://www.omicsonline.org/open-access/amphetamines-potent-recreational-drug-of-abuse-2155-6105-1000330.pdf | title = Amphetamines: Potent Recreational Drug of Abuse | org = Journal of Addiction Research & Therapy | date = 21 July 2017 | authorlist = | id = 768596741 | comments = At least half of this "review article" is composed of copy/pasted article text with superficial revision, tables (2 total), and diagrams (2 total) from [[Amphetamine]] and [[Adderall#Mechanism of action]] without attribution to these articles.}}
{{Backwardscopyvio | url = https://www.omicsonline.org/open-access/amphetamines-potent-recreational-drug-of-abuse-2155-6105-1000330.pdf | title = Amphetamines: Potent Recreational Drug of Abuse | org = Journal of Addiction Research & Therapy | date = 21 July 2017 | id = 768596741 | comments = At least half of this "review article" is composed of copy/pasted article text with superficial revision, tables (2 total), and diagrams (2 total) from [[Amphetamine]] and [[Adderall#Mechanism of action]] without attribution to these articles.}}


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== External links modified ==
== Shortages ==


Shortages section needs a lot of work. FDA actually first reported the shortage in I think may or june, then declared it to be over in I believe September. The actual shortage started back in 2021. There are references that mention that if people look hard enough.
Hello fellow Wikipedians,


It needs to be noted that shortages as reported by the FDA are based on voluntary reporting by manufacturers and is not required. And therefore do not accurately represent shortages as seen by consumers. If they choose not to report then it goes without being recognized by the FDA. So, when Teva waited till late spring I think of 2022 to bother to report their shortage, there was already a profound effect on users having issues getting their script filled and they got back lash for waiting too long. Also, manufactures tend to downplay the extent of the issue and underestimate the time to the shortage being over. All this is documented in articles if people look. I don't have the time to go back and dig every thing up again.
I have just modified {{plural:2|one external link|2 external links}} on [[Adderall]]. Please take a moment to review [https://en.wikipedia.org/enwiki/w/index.php?diff=prev&oldid=742506934 my edit]. If you have any questions, or need the bot to ignore the links, or the page altogether, please visit [[User:Cyberpower678/FaQs#InternetArchiveBot|this simple FaQ]] for additional information. I made the following changes:
*Added archive https://web.archive.org/web/20070804233232/http://www.homeoffice.gov.uk/drugs/drugs-law/Class-a-b-c/ to http://www.homeoffice.gov.uk/drugs/drugs-law/Class-a-b-c/
*Added archive https://web.archive.org/web/20051205125434/http://www.incb.org/pdf/e/list/green.pdf to http://www.incb.org/pdf/e/list/green.pdf


And if putting a shortages section. If people don't know when the other shortages were over the years, should at least mention that the most recent one is not the only one. I know there was one I believe in 2012 when I think Shire redirected the API to their Vyvanse instead of distributing it to the generic companies as they were contracted to. Causing the shortage.
When you have finished reviewing my changes, please set the ''checked'' parameter below to '''true''' or '''failed''' to let others know (documentation at {{tlx|Sourcecheck}}).


There is a document in 2015 to congress from an investigation into the DEA noting all their shortcomings and failures in regards to their control of the amphetamine API and quota system from the 2012 shortage. Which can also show how they impacted and again exacerbated the current shortage.
{{sourcecheck|checked=false}}


There was at least 1 other shortage but not as bad between the 2012 and current one. Forget when it was exactly.
Cheers.—[[User:InternetArchiveBot|'''<span style="color:darkgrey;font-family:monospace">InternetArchiveBot</span>''']] <span style="color:green;font-family:Rockwell">([[User talk:InternetArchiveBot|Report bug]])</span> 03:31, 4 October 2016 (UTC)
So, I think the shortages section should be renamed to "Shortage 2021 to 2023" because "Shortages" implies more than one, and only 1 is listed skipping all the others, and the info is incorrect at that to begin with. Until someone feels like putting in effort for either title, it should be removed. [[Special:Contributions/2601:86:600:A85:14B1:C34D:88DA:1EF1|2601:86:600:A85:14B1:C34D:88DA:1EF1]] ([[User talk:2601:86:600:A85:14B1:C34D:88DA:1EF1|talk]]) 05:26, 16 May 2023 (UTC)


== PHARMA EDITORS TO THIS PAGE ==
== Please correct... ==


(1) Please correct the following appearing content to a scholarly understanding of molecular microbiology:
This page paints adderall way too much more positively than is accurate. I believe pharma people may be editing this page! Please check! <!-- Template:Unsigned IP --><small class="autosigned">—&nbsp;Preceding [[Wikipedia:Signatures|unsigned]] comment added by [[Special:Contributions/209.2.213.191|209.2.213.191]] ([[User talk:209.2.213.191#top|talk]]) 06:57, 15 November 2016 (UTC)</small> <!--Autosigned by SineBot-->
:You need to be a ''little more specific'' about what you believe the problem is here. [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 17:30, 15 November 2016 (UTC)
::This article in not neutral in tone! The article repeatedly refers to therapeutic doses in a positive and comforting tone, e.g. "Reviews of clinical stimulant research have established the safety and effectiveness of long-term amphetamine use for ADHD." in the part on medical uses and " The review indicated that withdrawal symptoms are associated with the degree of dependence, suggesting that therapeutic use would result in far milder discontinuation symptoms." in under dependence and withdrawal. The first statement is far too certain in my opinion and the second one seems to me to be trying to comfort a reader by being weaselly. These articles show there is some doubt about the safety of long term adderall consumption (at near therapeutic dosage) and that there is some concern about the effects of adderall on young children: https://www.ncbi.nlm.nih.gov/pubmed/27579185, http://jpet.aspetjournals.org/content/315/1/91.long, http://journal.frontiersin.org/article/10.3389/fnsys.2014.00038/full. The article is not neutral in tone and it gives undue weight to a pro-adderall POV. Forgot to sign: [[User:I am a rock (and an island)|I am a rock (and an island)]] ([[User talk:I am a rock (and an island)|talk]]) 14:32, 18 November 2016 (UTC)
::Also, while this probably isn't a good Wikipedia source, this link has a fair amount of information: https://www.quora.com/What-are-the-long-term-effects-of-Adderall-Dexedrine-or-Ritalin-use. [[User:I am a rock (and an island)|I am a rock (and an island)]] ([[User talk:I am a rock (and an island)|talk]]) 14:46, 18 November 2016 (UTC)


:"Since the total number of microbial and viral cells..."


(2) Please do the same to the source of the content, in the referenced section of the Amphetamines article.
:::{{Ping|I am a rock (and an island)}} I've attempted to address your concerns accordingly:
:::*The case report that you cited on [https://www.ncbi.nlm.nih.gov/pubmed/27579185 the cardiovascular implications of stimulant medications for adult ADHD] discusses the cardiovascular effects of amphetamine pharmaceuticals in adults who have been prescribed these drugs in spite of evidence suggesting that they have a preexisting cardiovascular condition. As noted in this article, [[heart disease]] is an [[absolute contraindication]] for any pharmaceutical amphetamine, meaning these drugs should not be prescribed to individuals with these conditions under ANY circumstances. The article currently indicates that amphetamine pharmaceuticals do not increase the risk of serious adverse cardiovascular events in children, young adults, or adults and cites two FDA-commissioned studies and the two associated FDA information pages on the cardiovascular effects of these drugs in those age groups (the current statement in the article's "Side effects" section: {{tq|USFDA-commissioned studies from 2011 indicate that in children, young adults, and adults there is no association between serious adverse cardiovascular events ([[sudden cardiac death|sudden death]], [[myocardial infarction|heart attack]], and [[stroke]]) and the medical use of amphetamine or other ADHD stimulants.{{#tag:ref|<ref>{{cite web | title=FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children and young adults | date=20 December 2011 | url=http://www.fda.gov/Drugs/DrugSafety/ucm277770.htm | work=United States Food and Drug Administration | accessdate=4 November 2013}}</ref><ref name="pmid22043968">{{cite journal |vauthors=Cooper WO, Habel LA, Sox CM, Chan KA, Arbogast PG, Cheetham TC, Murray KT, Quinn VP, Stein CM, Callahan ST, Fireman BH, Fish FA, Kirshner HS, O'Duffy A, Connell FA, Ray WA | title = ADHD drugs and serious cardiovascular events in children and young adults | journal = N. Engl. J. Med. | volume = 365 | issue = 20 | pages = 1896–1904 |date=November 2011 | pmid = 22043968 | doi = 10.1056/NEJMoa1110212 }}</ref><ref>{{cite web | title=FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in adults | date=15 December 2011 | url=http://www.fda.gov/Drugs/DrugSafety/ucm279858.htm | work=United States Food and Drug Administration | accessdate=4 November 2013}}</ref><ref name="pmid22161946">{{cite journal |vauthors=Habel LA, Cooper WO, Sox CM, Chan KA, Fireman BH, Arbogast PG, Cheetham TC, Quinn VP, Dublin S, Boudreau DM, Andrade SE, Pawloski PA, Raebel MA, Smith DH, Achacoso N, Uratsu C, Go AS, Sidney S, Nguyen-Huynh MN, Ray WA, Selby JV | title = ADHD medications and risk of serious cardiovascular events in young and middle-aged adults |date=December 2011 | journal = JAMA | volume = 306 | issue = 24 | pages = 2673–2683 | pmid = 22161946 | pmc = 3350308 | doi = 10.1001/jama.2011.1830 }}</ref>|group="sources"}}}}). Since this article already covers the cardiovascular disease contraindication and does not suggest anywhere that the use of amphetamine pharmaceuticals in individuals with preexisting cardiovascular conditions is safe, there doesn't appear to be anything in this study that the article doesn't already assert. I unfortunately can't cite the [[case report]] study itself since it's not a medical [[literature review]] (see [[WP:MEDRS]], the Wikipedia policy that covers the type of medical studies which can be used as references for medical information); however, I have attempted to clarify the current article text in that section by stating that amphetamine pharmaceuticals are still contraindicated in individuals with preexisting cardiovascular disease, citing more appropriate medical sources ('''revised in [[special:diff/750280759/750281192]]''').
:::*Since the latter clause in the sentence on dependence that you mentioned doesn't appear to be directly supported by the cited reference, I've revised the sentence accordingly ('''revised in [[special:diff/749932190/750277107]]'''); however, the former clause is directly supported by the cited reference (quote from the cited [[Cochrane review]]: "{{tq|The severity of withdrawal symptoms is greater in amphetamine dependent individuals who are older and who have more extensive amphetamine use disorders (McGregor 2005).}}").
:::*The paragraph in this article which covers the safety and efficacy of stimulant medications for ADHD, including the particular sentence that you mentioned ({{tq|Reviews of clinical stimulant research have established the safety and effectiveness of long-term amphetamine use for ADHD.<ref name="Millichap">{{cite book | author = Millichap JG | editor = Millichap JG | title = Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD | year = 2010 | publisher = Springer | location = New York, USA | isbn = 9781441913968 | pages = 121–123, 125–127 | edition = 2nd | chapter = Chapter 9: Medications for ADHD | quote = Ongoing research has provided answers to many of the parents’ concerns, and has confirmed the effectiveness and safety of the long-term use of medication.}}</ref><ref name="Long-term 2015">{{cite journal | vauthors = Arnold LE, Hodgkins P, Caci H, Kahle J, Young S | title = Effect of treatment modality on long-term outcomes in attention-deficit/hyperactivity disorder: a systematic review | journal = PLoS ONE | volume = 10 | issue = 2 | pages = e0116407 | date = February 2015 | pmid = 25714373 | pmc = 4340791 | doi = 10.1371/journal.pone.0116407 | quote = The highest proportion of improved outcomes was reported with combination treatment (83% of outcomes). Among significantly improved outcomes, the largest effect sizes were found for combination treatment. The greatest improvements were associated with academic, self-esteem, or social function outcomes. }}</ref><ref name="Long-Term Outcomes Medications">{{cite journal |vauthors=Huang YS, Tsai MH | title = Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge | journal = CNS Drugs | volume = 25 | issue = 7 | pages = 539–554 |date=July 2011 | pmid = 21699268 | doi = 10.2165/11589380-000000000-00000 | quote = Recent studies have demonstrated that stimulants, along with the non-stimulants atomoxetine and extended-release guanfacine, are continuously effective for more than 2-year treatment periods with few and tolerable adverse effects. The effectiveness of long-term therapy includes not only the core symptoms of ADHD, but also improved quality of life and academic achievements. The most concerning short-term adverse effects of stimulants, such as elevated blood pressure and heart rate, waned in long-term follow-up studies.}}</ref>}}), is directly supported by all of its references. The first reference for that sentence is a professional level textbook that covers the safety and efficacy of ADHD medications in several sections of the textbook that are dedicated to those topics; the latter two references for the sentence are medical reviews which examine the long-term efficacy (2nd ref) and long-term safety+efficacy (3rd ref) of ADHD stimulants. All three references base their conclusions on [[randomized controlled trials]] (RCTs) that studied the safety and efficacy of stimulants medications for ADHD in humans; RCTs are the type of [[primary source]] which provide the best evidence for drawing conclusions on the safety and efficacy of pharmaceuticals (see [[WP:MEDRS#Assess evidence quality]]). Since all three references are fairly conclusive and base their conclusions on high quality evidence, I'd need to cite a [[literature review|review]] or [[meta-analysis]] of RCTs which contains a contradictory conclusion about the safety and efficacy of amphetamine pharmaceuticals for the treatment of ADHD in order to make a contradictory assertion in this article. I am open to revising that sentence based upon what is stated in these references though. If you need access to any of the three refs, let me know and I'll upload the article to an external website and provide a link or (in the case of the textbook) quote the relevant sections for you.
:::*The study you linked which covers the effects of amphetamine in adult nonhuman primates ("[https://www.ncbi.nlm.nih.gov/pubmed/16014752 Amphetamine Treatment Similar to That Used in the Treatment of Adult Attention-Deficit/Hyperactivity Disorder Damages Dopaminergic Nerve Endings in the Striatum of Adult Nonhuman Primates]") is a primary source which can't be cited directly, per [[WP:MEDRS]]; however this article currently covers the findings of this study, citing a medical review which included the study, in the "Medical uses" section, which states:<blockquote>{{tq|Long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal [[Dopamine receptor|dopamine system]] development or nerve damage,<ref name="pmid22392347">{{cite journal |vauthors=Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L |title=Toxicity of amphetamines: an update |journal=Arch. Toxicol. |volume=86 |issue=8 |pages=1167–1231 |date=August 2012 |pmid=22392347 |doi=10.1007/s00204-012-0815-5 |url=}}</ref><ref name="AbuseAndAbnormalities">{{cite journal|vauthors=Berman S, O'Neill J, Fears S, Bartzokis G, London ED | title=Abuse of amphetamines and structural abnormalities in the brain | journal=Ann. N. Y. Acad. Sci. | date = October 2008 | volume= 1141 | issue= | pages= 195–220 | pmid=18991959 | doi=10.1196/annals.1441.031 | pmc=2769923 }}</ref> but, in humans with ADHD, pharmaceutical amphetamines appear to improve brain development and nerve growth.<ref name="Neuroplasticity 1">{{cite journal |vauthors=Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K |title=Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects |journal=JAMA Psychiatry |volume=70 |issue=2 |pages=185–198 |date=February 2013 |pmid=23247506 |doi=10.1001/jamapsychiatry.2013.277 |url=}}</ref><ref name="Neuroplasticity 2">{{cite journal |vauthors=Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J |title=Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies |journal=J. Clin. Psychiatry |volume=74 |issue=9 |pages=902–917 |date=September 2013 |pmid=24107764 |doi=10.4088/JCP.12r08287 |url= |pmc=3801446}}</ref><ref name="Neuroplasticity 3">{{cite journal | title=Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects. | journal=Acta psychiatrica Scand. | date=February 2012 | volume=125 | issue=2 | pages=114–126 | pmid=22118249 |vauthors=Frodl T, Skokauskas N | quote = Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure. | doi=10.1111/j.1600-0447.2011.01786.x}}</ref> Reviews of [[magnetic resonance imaging]] (MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right [[caudate nucleus]] of the [[basal ganglia]].<ref name="Neuroplasticity 1" /><ref name="Neuroplasticity 2" /><ref name="Neuroplasticity 3" />}}</blockquote>
:::*The [https://www.quora.com/What-are-the-long-term-effects-of-Adderall-Dexedrine-or-Ritalin-use quora source that you linked] doesn't satisfy [[WP:MEDRS]] (it's not a medical source) or even [[WP:RS]] for that matter, so it can't be used to cite any medical or even non-medical statements in this article.
:::*The study that you cited on the use of amphetamine pharmaceuticals as a nootropic ([https://www.ncbi.nlm.nih.gov/pubmed/?term=24860437 Performance enhancement at the cost of potential brain plasticity: neural ramifications of nootropic drugs in the healthy developing brain.]) is a medical review, so <u>it can be used to cite statements in this article</u>; however, I'm not sure what statement(s) you'd like to see added to this article from the information that is covered in this review. Can you clarify?
:::Let me know if the changes that I've made have addressed your concerns. I also need your input to address potential content additions related to the last bullet above. If you have any other suggestions for content additions in the article, it would help if you familiarize yourself with [[WP:MEDRS]] so that you know what citations can be used to cite medical information in Wikipedia articles. To very briefly summarize the relevant sections of that policy, acceptable sources for citing medical statements in Wikipedia articles include: peer-reviewed medical reviews and meta-analyses that have been recently published in a pubmed-indexed journal [[WP:MEDDATE|(articles that have been published within the past 5 years are considered ideal - 10 years is typically considered the upper age limit)]], recently published (again, ideally up to 5 years old, 10 year limit) college/graduate/professional level academic textbooks, and content that is published on the websites of most professional medical organizations (e.g., the [[USFDA]], the [[WHO]], [[NICE]], etc.).
:::Also, if you'd like to read any of the medical reviews that are cited in this article but require payment to access, I'd be happy to upload those reviews to an external website and provide a link for you to download or read them; just let me know which sources you need. [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 22:35, 18 November 2016 (UTC)
::::{{Ping|Seppi333}} Thank you for replying so quickly. Also, I'm sorry I didn't familiarise myself with [[WP:MEDRS]] before I decided to criticise an article which, having skimmed your profile, I now know that you wrote.
::::*The [[special:diff/750280759/750281192|first change you made]] balances things out with regard to the first sentence I initially mentioned, IMO. The [[special:diff/749932190/750277107|second change]] increases neutrality, but to me it does seem to decrease clarity. It is very briefly being unclear what the association between the degree of dependence and withdrawal symptoms might be. Could the sentence be changed again to read: "The review indicated that the severity of withdrawal symptoms is high or low in people with correspondingly high or low degree of dependence." Or something similar?
::::*Adderall is not mentioned specifically in the [http://journal.frontiersin.org/article/10.3389/fnsys.2014.00038/full review in my first reply to you]. In the conclusion the author expresses uncertainty about the safety of stimulants in general for adolescents and children, which is relevant to the 'safety and effectiveness' sentence. On the other hand, the article in question is not about adderall, so the cherry picking would probably not constitute a reliable source.
::::*The second source<ref name="Long-term 2015">{{cite journal | vauthors = Arnold LE, Hodgkins P, Caci H, Kahle J, Young S | title = Effect of treatment modality on long-term outcomes in attention-deficit/hyperactivity disorder: a systematic review | journal = PLoS ONE | volume = 10 | issue = 2 | pages = e0116407 | date = February 2015 | pmid = 25714373 | pmc = 4340791 | doi = 10.1371/journal.pone.0116407 | quote = The highest proportion of improved outcomes was reported with combination treatment (83% of outcomes). Among significantly improved outcomes, the largest effect sizes were found for combination treatment. The greatest improvements were associated with academic, self-esteem, or social function outcomes. }}</ref> cited for the efficacy and safety sentence in my opinion is fairly conclusive but this is a quote from the conclusion:
::::"This suggests that effects of treatment are greatest near the time when treatment has occurred, consistent with a recent review that analyzed data from five randomized controlled trials, including the MTA study, and concluded that there is moderate to strong evidence for improvement in academic outcomes for follow-up times up to 14 months but that effect sizes may decrease thereafter."
::::This quote and the fact that the article uses studies that measure the effectiveness of treatment while the treatment is taking place or not too long after the treatment has finished suggest to me that we should draw from this study that treatment (drug or combination) is effective while it is taking place and shortly after. Also, effectiveness in the review is not specified to be about ADHD symptoms and I feel this should be made clear. As well as this, there are a significant number of studies in most of the breakdowns that show no statistically significant benefit of treatment with stimulants so I think the statement should be modified so it sounds less clear cut.
::::I do not have access to either of the other sources, but thank you for offering to upload them externally but it is not necessary.
::::Having said that, I realise the abstract of a review does not contain the whole review. However, in the abstract of the other review that is cited for this sentence, the only statement about efficacy and safety is one about this for up to two years (of treatment?).
::::*I am not sure what the sentence should be changed to but I think it should be changed. I haven't looked at the sources very thoroughly so I can imagine we might disagree further. Also, please review the new, terrible phrasing of the sentence I amended above. I would understand if that sentence was kept as it is. Apologies for such a long reply and taking so long to reply.<!-- Template:Unsigned --><small class="autosigned">—&nbsp;Preceding [[Wikipedia:Signatures|unsigned]] comment added by [[User:‎I am a rock (and an island)|‎I am a rock (and an island)]] ([[User talk:‎I am a rock (and an island)#top|talk]] • [[Special:Contributions/‎I am a rock (and an island)|contribs]]) </small><small>[[User:BallenaBlanca|BallenaBlanca]] [[Image:BallenaBlanca.jpg|25px]] [[Image:Blue Mars symbol.svg|12px]] [[User talk:BallenaBlanca|<small>(Talk)</small>]] 23:57, 19 November 2016 (UTC)</small>
::::Thank you to the person who signed for me. I just realised I am probably being quite rude and I don't know very much about this subject. I did not write the first comment in this subsection, but when I was reading the article it struck me as being quite biased. Sorry if I am being rude. Also sorry for apologising ten times. [[User:I am a rock (and an island)|I am a rock (and an island)]] ([[User talk:I am a rock (and an island)|talk]]) 03:55, 20 November 2016 (UTC)


(3) More broadly, please consider whether this article needs such a long introductory paragraph as the one containing this sentence. The shorter following paragraph is indeed relevant to the article. In this editor's opinion, there is no need to spend as much time defining a field as presenting a specific result from it; the content giving explanatory and defining information (e.g., indicating numbers of microbial cells in the microbiome, etc.) is superfluous.
::::::I think this revision should address your concerns about the ambiguity in the sentence on dependence: [[Special:diff/750435406/750621547]]; if not, let me know. I'll respond to your other points sometime later today or tomorrow - need to log off for now. [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 22:18, 20 November 2016 (UTC)


The entire first paragraph here could be replaced by one sentence with a wikilink and a citation or two (serving as an introductory sentence to the content of the current second paragraph). [[Special:Contributions/73.8.193.28|73.8.193.28]] ([[User talk:73.8.193.28|talk]]) 00:22, 3 December 2023 (UTC)
::::::Sorry about the delayed reply. I haven't forgotten about this. I'll follow up once I get home later tonight. [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 23:37, 22 November 2016 (UTC)
:::::::I think it would be reasonable to state that the improvements in functional outcomes (e.g., academic, self-esteem, social function, etc.) that result from long-term stimulant therapy may decrease over time after treatment has stopped. The current article text is referring to the safety and efficacy of ''continuous'' stimulant therapy over arbitrarily long time horizons (e.g., lifelong treatment), so that should probably be clarified as well.
:::::::I also think that it would be reasonable to say that most but not all ADHD-related treatment outcomes improve with long-term stimulant therapy, per the review's conclusion.
:::::::While the review you've read doesn't examine the efficacy of pharmacotherapy for core ADHD symptoms, the [https://docs.google.com/viewer?a=v&pid=sites&srcid=ZGVmYXVsdGRvbWFpbnxzZXBwaWx1cnZlc3BhbmNha2VzfGd4OjNhMzBjOGJiN2E4YjQ2OTg other review] which cites that sentence does cover the long-term efficacy of continuous stimulant therapy for core ADHD symptoms. Per its conclusion: {{tq|Recent studies have demonstrated that stimulants, along with the non-stimulants atomoxetine and extended-release guanfacine, are continuously effective for more than 2-year treatment periods with few and tolerable adverse effects. The effectiveness of long-term therapy includes not only the core symptoms of ADHD, but also improved quality of life and academic achievements. The most concerning short-term adverse effects of stimulants, such as elevated blood pressure and heart rate, waned in long-term follow-up studies. The current data do not support the potential impact of stimulants on the worsening or development of tics or substance abuse into adulthood. In the longest follow-up study (of more than 10 years), lifetime stimulant treatment for ADHD was effective and protective against the development of adverse psychiatric disorders.}}
:::::::Anyway, I'll make these changes sometime within the next day or two and follow up here once I'm done. [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 08:02, 23 November 2016 (UTC)


== Insufflation ==
::::::::Thank you for uploading the other review and for putting up with my being annoying. I agree with what you've said about functional outcomes, ADHD-related outcomes and ADHD core symptoms outcomes. With respect to continuous treatment over a very long period of time, the reviews give the impression to me that outcomes would be similar to outcomes of treatment over a long period of time, but in the study [https://docs.google.com/viewer?a=v&pid=sites&srcid=ZGVmYXVsdGRvbWFpbnxzZXBwaWx1cnZlc3BhbmNha2VzfGd4OjNhMzBjOGJiN2E4YjQ2OTg you have uploaded], there is the following quote: {{tq|There are very few controlled long-term studies of more than 5 years of treatment for childhood ADHD,}} and from Table III the maximum duration of treatment referred to in the review is about 12 years. There is a similar statement about adult ADHD and the maximum duration of treatment mentioned is 2 years. The review concludes in both cases that treatment is safe and effective within these time frames. In [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340791/pdf/pone.0116407.pdf the other review] the mean duration of treatment for studies included is 7.1 years and I cannot find the maximum length of treatment duration, but since it is not made clear what this is, I think it is fair to assume the review doesn't intend to draw conclusions about treatment over very long periods of time? I am very aware that I am being incredibly annoying, but I do think it is reasonable to make clear that it is believed by the scientists who conducted these reviews (which it does seem to be?) that continuous treatment is safe and effective over very long periods but that this is not an established fact.
Why is insufflation listen as a method of administration of adderall in the sidebar?
::::::::Thanks for hearing me out on this. [[User:I am a rock (and an island)|I am a rock (and an island)]] ([[User talk:I am a rock (and an island)|talk]]) 21:12, 23 November 2016 (UTC)
[[User:Themckinlay|Themckinlay]] ([[User talk:Themckinlay|talk]]) 13:52, 2 August 2024 (UTC)


== Article is biased. ==
{{od}}{{ping|I am a rock (and an island)}} I'm really sorry for the long-delayed follow up. I've been really busy since I last posted due to the US thanksgiving holiday and work; I intend to update the article <s>by tomorrow night at the latest</s> on Friday (edit: as of Friday afternoon, I'll no longer be preoccupied with off-wiki responsibilities). In any event, I agree with you; the statements about long-term efficacy should be clarified to reflect what you and I have mentioned above. I expect that it'll take me 15-30 minutes to cover what we have discussed once I start working on this, depending upon how much detail I go into. [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 01:16, 1 December 2016 (UTC); Updated 04:44, 2 December 2016 (UTC)
:{{Ping|I am a rock (and an island)}} I've made a first attempt at addressing the issues we've discussed: [[Special:diff/751010255/752868507]]. Do you have any comments on what I've added or have any specific suggestions for revision or other additions? I expect to revise this further later. Also, following up on your last reply: I don't really have a problem with saying that the safety+efficacy of stimulant therapy beyond the maximum study duration aren't established, but I can't actually state this unless one of the cited reviews makes this statement due to the [[WP:Verifiability]] policy. In order to cover this, we'd need a review that states that the long(er)-term effects of stimulant therapy for ADHD beyond time X are unknown. [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 21:56, 3 December 2016 (UTC)
===Arbitrary section break===
:: I think the changes you have made so far are quite fair, but I would like to see it mentioned that the improvement of non-core symptoms might lessen once treatment has stopped as we discussed above. Also, I agree that the need for verifiability means that it can't be said that the level of safety and efficacy isn't known past a certain duration of treatment, but I also think it is not possible to verify that continuous treatment is always effective as I think the article currently implies, because as in my last reply neither of the reviews cited currently can confirm this. Could the 'safety and efficacy statement' (at least in the Adderall article) be changed, maybe to read: "...continuous amphetamine use over time periods reviewed for..." in view of this? I am genuinely not trying to draw this out unnecessarily by the way. Having said that (sorry), do you think it is reasonable to include in the introduction that Adderall is a brand name? In these similar articles ([[Citalopram|1]],[[Ritalin|2]],[[Dexmethylphenidate|3]],[[Modafinil|4]]) brand names are mentioned and called brand names in the introduction. [[User:I am a rock (and an island)|I am a rock (and an island)]] ([[User talk:I am a rock (and an island)|talk]]) 16:59, 4 December 2016 (UTC)
:::{{ping|I am a rock (and an island)}} Thanks for the feedback!
:::*W.r.t. the long-term safety and efficacy of continuous treatment, this is not something that ''we'' are stating as our own [[WP:OR|original conclusions based upon other research]]; it's what the cited reviews explicitly state as a conclusion based upon primary research and that we are repeating in our own words. The key here is to ensure that we faithfully and accurately restate what is explicitly concluded in the cited review(s) so that our statements are directly supported by and consistent with the cited review(s). This is why I wrote "<u>based upon the longest follow-up studies conducted to date</u>, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a substance use disorder as an adult" instead of the same sentence without the underlined clause. The review which cites that sentence is not implying that longitudinal cohort-based studies have been conducted from childhood to the time of death in ADHD individuals; rather, it states in its conclusion ({{tq|In the longest follow-up study (of more than 10 years), lifetime stimulant treatment for ADHD was effective and protective against the development of adverse psychiatric disorders}}) that, based upon the longest 12 year study, these drugs do not lose efficacy and therefore there's no clear reason to assume that from anytime during 13 years of treatment onward, these drugs somehow lose efficacy for controlling the core symptoms of ADHD. It seems very odd to me to assume otherwise as well considering that after 12 years of treatment, most children that started using stimulants are adults (i.e., at least 18 years old) who are probably in their early 20s. By that time, an individual's brain is no longer in its developmental stages, although the brain does still change throughout the remainder of an adult's life through [[activity-dependent neuroplasticity]] and drug/trauma/pathogen/disease-induced [[neuroplasticity]] (the latter form of plasticity is typically but not necessarily pathological).<br />With that in mind, I'd be okay with rephrasing the underlined clause from above as "based upon the longest follow-up studies with durations of up to 12 years" instead of "based upon the longest follow-up studies conducted to date" if you believe that this would be an improvement.
:::*<s>I think it would be a bit confusing to state that Adderall is a brand name because it's also commonly used to refer to all generic mixtures which contain the same ratio of salts which compose Adderall (these are the 4 [technically 3] salts listed beneath "Combination of" in the drugbox). Generic Adderall doesn't have a standardized nonproprietary name, which is why this article doesn't refer to generic Adderall as anything but "generic Adderall". Most brand name drugs that have internationally accepted medical uses or are FDA-approved respectively have an [[international nonproprietary name]] (INN) or [[United States Adopted Name]] (USAN). Adderall is an exception, since it does not have either an INN or a USAN (for this reason, this article uses a brand name instead of a generic name as the page title; normally drug articles use the INN as the page title, per [[MOS:PHARM]]). It's is worth noting that Adderall's FDA-listed generic name is '''dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine sulfate and amphetamine aspartate''', which is indicated in the note next to the word "Adderall" in the 1st lead sentence.<br />With that in mind, would it suffice if we were to state that Adderall is a brand name and a term which refers to generic drugs which contain the same ratio of amphetamine salts that compose brand name Adderall? I believe that I could cite that statement using the FDA-approved prescribing information for brand-name and generic Adderall IR pharmaceuticals, but I'd need to double check.</s>
:::*::{{ping|I am a rock (and an island)}} Follow-up comment: {{facepalm}} ... Nevermind what I said previously, I just realized that I actually did what you asked in the [[amphetamine]] article, but not this article. I've replaced note 1 in this article with the relevant note from the amphetamine article. See '''[[Special:diff/753370797/753374547]]'''. [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 20:04, 6 December 2016 (UTC)
:::*W.r.t. the reduction in outcome improvements from long-term stimulant therapy following the cessation of pharmacotherapy, this is something that I still intend to add to the article. I didn't include it in my last edit because I couldn't figure out a way to fit it in without making the section read clumsily (aside: the [[amphetamine]] article is a [[WP:featured article]], so I can't add content without regard to the readability of the prose). I still intend to cover this once I reorganize the content in the 2nd/3rd paragraphs of the [[Amphetamine#Medical]] section. I'll ping you once I get around to reorganizing this and adding that content.
:::Also, I really don't mind discussions like this as long as the intended aim of the discussion is to improve the article (e.g., improve the accuracy/readability/clarity of the article text in this or other sections), so please don't apologize! I'm happy to work with you here as long as this is our mutual goal. So, if you have any additional suggestions, concerns, comments, or questions about the article text, feel free to mention them. I really don't mind. {{P|1}} [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 17:36, 5 December 2016 (UTC)
::::{{ping|Seppi333}} Sorry for taking so long to reply--I put one thing off and then I end up putting everything off. Also, I appreciate what you've said in the last paragraph of the above reply! I think our goals agree. Having read what you've written in the first bullet point above and from the perspective of readability and honest representation of facts, I don't think we should change the sentence. It seems like an honest enough representation of the facts as it is and adding the longest study's duration could be a bit distracting. [[User:I am a rock (and an island)|I am a rock (and an island)]] ([[User talk:I am a rock (and an island)|talk]]) 19:58, 7 December 2016 (UTC)


Article is very biased. Same rhetoric propagated all too often. Negative effects are in context of abuse. Adderall can cause the same issues at prescribed levels as at the abused levels, only slower. Always stating the negative in terms of abuse is a "blame the victim" narrative for anyone with issues at therapeutic doses. Even ICD10 and ICD11 codes for side effects from amphetamine states it can occur at therapeutic prescribed doses. Although the listed number of possible side effects is quite limiting. Research, especially in adults has shown this too.
===Section references===
;Grouped references
{{reflist|group=sources}}
;References
{{reflist}}


I apologize for not having all the links for all these things as this is not being written on my computer.
== This whole article reads like a brochure ==
So much praise and carefully reassuring phrasing, for something that garners considerable mistrust (at least outside the USA) and has very little information about long-term use.


Article mentions young children who start on Adderall are less likely to become addicts when they get older. What they fail to mention is that starting in adolescents or adulthood, people are more likely to become addicts as they are more willing to self medicate or seek a euphoric dose.
The whole first paragraph supposedly describing side-effects is, in fact, an explanation of how they're not really that serious (despite describing them as many and varied).


Missing is one of the primary effects of amphetamine is the AMPA/NMDA antagonism causing glutamate release. And believed by many researchers to be the primary way amphetamine builds tolerance.
I know there are well-funded interests who have a vested interest in biasing this page (and it's clearly working) but can we at least try to look like a NPOV policy? [[Special:Contributions/86.153.54.114|86.153.54.114]] ([[User talk:86.153.54.114|talk]]) 23:13, 27 December 2016 (UTC)
:NPOV means we have to give [[WP:DUEWEIGHT]] to viewpoints. You'll have to be more specific. What is the article currently missing? [[User:Sizeofint|Sizeofint]] ([[User talk:Sizeofint|talk]]) 23:34, 27 December 2016 (UTC)
:: Any particular reason to move this to the bottom of the talk section? Don't worry, I fixed that for you. As to the article.. No mention whatsoever of it being over-prescribed http://www.recoveryanswers.org/blogs/adderall/ https://www.minnpost.com/second-opinion/2016/09/overprescribing-drugs-adult-adhd-causing-trail-misuse-addiction-and-death?


Also lacking is many of the ways amphetamine causes downregulation and damage.
::Plus, NPOV is not only about giving due weight, it's also about writing in a neutral tone. Eg not this: "The risk of developing an addiction is insignificant when Adderall is used as prescribed at fairly low daily doses". There are many, many sources online chronicling people becoming addicted from prescribed doses.
--adderall can be exciteotoxic to the NMDA/glutamatergic pathways. Over excitement causes downregulation of receptors and excess ion flux causes oxidative stress in the cell that can lead to disregulation or even apoptosis. Excess glutamate triggers extrasynaptic NMDA receptors which is the trigger for the apoptosis cascade. Many researchers believe this to be the primary way amphetamine builds tolerance. And why some therapist prescribe the NMDA uncompetitive antagonist memantine to prevent or reduce tolerance.
--Does mention the phosphorilization of DAT and NAT. But does not mention that this is acute tolerance and causes a need for a higher blood API concentration in the afternoon just to maintain the same therapeutic efficiency as the morning. And why the standard recommended dosage is the same dose separated by about 4 hours, which nearly doubles the BAC to maintain steady therapeutic effect and how Adderall XR was designed. I do have an article for the readily available. Shows acute tolerance, therapeutic dose curve during the day. But before they understood acute tolerance is from phosphorilization of DAT and NAT and likely other pathways like NMDA.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2547091/
--VMAT2 can get downregulated or cause dysfunction.
--Amphetamine can diffuse through the cell wall, doesn't just use DAT or NAT transports. And can diffuse through mitochondria wall which it can cause oxidative stress in mitochondria.
--Can't recall if MOA antagonism was mentioned, but it can cause damage or downregulation too.
--A lot of the catecholamines get stuck in the cytosol which auto-oxidizes leading to oxidative stress. As does excess in the synapse and extra-synaptic space.
--Does regulation of tyrosine hydroxylase has been shown can happen with long term use.
--A know there are other neurological factors I don't recall.


Endocrine side effects was not even mentioned. Less research but it does exist. Even the FDA approved accompanying literature mentions endocrine effects but very lacking in longer term effects.
::I'll assume good faith on your part, but the overly-optimistic tone of this article at present makes it nothing more than a marketing tool to convince parents when they first start researching the drug. [[Special:Contributions/86.153.54.114|86.153.54.114]] ([[User talk:86.153.54.114|talk]]) 23:54, 27 December 2016 (UTC)
--A THE and cortisol decrease during the day. amphetamine has the opposite effect on it.
--Can cause testosterone/estrogen imbalance in part due to weak estrogenic property of amphetamine. But likely due to other reasons too. Which in men has low T symptoms.
--Can decrease LH and FSH which can effect fertility.
--Can cause stimulant induced secondary gynecomastia. Which can be distinguished from other forms of gynecomastia by stimulant use, estrogen dominance, normal or low levels of LH and FSH.
--Can increase cAMP, which I don't recall for sure but may have been a side effect of high ACTH.
--There are some others I forget off the top of my head.


Only references an article in which it states higher dose users can take up to 4 weeks to recover from stopping medication. Doesn't mention that is not true for everyone and although not frequent, some people can take 6 months to a year, even from prescribed high doses. Has been shown in other studies that even at low doses there is a significant number of patients who show accumulated tolerance and stopping medication worsens ADHD symptoms for a while. Amphetamine can also cause irreversible damage for some people while addicts can also often make a full recovery.
:::Talk page sections are ordered chronologically by the creation date of each section when new sections are added via the "New section" tab, which is used by most editors. This page follows this convention.
:::When taken as prescribed, amphetamine doesn't sufficiently induce ΔFosB expression in the nucleus accumbens to allow it to accumulate. When it's taken in larger doses than a doctor has prescribed, Adderall can sufficiently induce that protein and allow it to accumulate. That causes an addiction. This is why most medical professionals insist strongly that patients only take the medication as prescribed.
:::I'm not sure what you mean by overly-optimistic tone; what statements are you referring to? [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 05:05, 28 December 2016 (UTC)
:::: "When it's taken in larger doses than a doctor has prescribed" So you're aware of how it's prescribed worldwide, and are comfortable making that statement based on what evidence?


There is some study on how adults respond differently to the medication, especially in the long run. But also acknowledge adult research is still lacking in many ways.
:::: As to the overly optimistic tone, I gave examples. If you'd like another, why does the "side-effects" section include disclaimers about how safe it is? (As do most other sections). You also haven't addressed the issue of being over-prescribed as per the links I referenced above [[Special:Contributions/86.153.54.114|86.153.54.114]] ([[User talk:86.153.54.114|talk]]) 16:05, 29 December 2016 (UTC)


Many studies on CNS stimulants stunting growth say on stopping medication, growth resumes and is unaffected. While other studies show a decrease final height even after stopping medication that is statistically significant compared to placebo group. Think on average it may have been a 1/2 inch shorter but not sure. Don't recall reading studies on children who stayed on longer after stunted growth was recognized. Which doesn't mention the underlying cause but likely something in the endocrine system.
:::::You don't seem to be aware that MAS/Adderall (the subject of this particular article) is only available in North America, specifically the US and Canada. Other ADHD medications such as [[dextroamphetamine]], [[lisdexamfetamine]], [[methylphenidate]], [[atomoxetine]], etc are more widely available worldwide; however, MAS/Adderall is not even near being available "worldwide" as you claim it to be.
:::::I'm not quite sure what you're trying to insinuate anyways, that doctors are prescribing too-high doses? Hah! Nowhere near the truth. Evidence? Well if you want truly "hard" evidence of what real-world prescribing practices look like, I recall reading more than a few scientific articles analyzing prescribing practices at a large scale, and I'm sure you're more than capable of going to pubmed and digging those articles up if you're truly interested in rational discourse... I am not here to spoon-feed you those particular type of refs though, so don't whine about me not citing them inline.
:::::If you actually meant evidence of MAS/Adderall's safety and efficacy at treating ADHD, well, I honestly don't feel obliged to back up that claim with any additional evidence - you can easily verify this claim over and over and over and over again if you start reading some of the major refs used in this article alone, and there's plenty more duplication of that proof (specifically and generally) in refs spread out across quite a few articles related to this subject...
:::::So you claim you gave examples. I see you mentioning the side effects descriptions (I disagree with your assessment - the side effects are described appropriately and comply with [[WP:PHARMMOS]] guidelines), then a claim made by you that Adderall is overprescribed which was backed by two completely unreliable and arguably very misleading sources (we require the use of a much higher standard of evidence on Wikipedia than you're probably used to - you'll need to come back with some quality sources if you want to continue arguing that angle), and then another claim that an entirely accurate statement ("The risk of developing an addiction is insignificant when Adderall is used as prescribed at fairly low daily doses") is false based off of your claim that anecdotal accounts to the contrary exist (indicating quite clearly that you urgently need to read [[WP:MEDRS]]).
:::::But hey, let's talk about anecdotes for a bit. Even if we considered these anecdotes to be a valid source, you would have to compensate for one huge glaring issue with most of these anecdotes - they are from people who were not using Adderall as prescribed. Indeed, I would bet that a significant portion of them never had a prescription for the drug in the first place, and that many others were faking symptoms of ADHD in order to obtain prescriptions under false pretenses for the explicit purpose of misusing the drug. A smaller number of them would be people who legitimately had a prescription for ADHD but voluntarily began misusing the drug for whatever reason. Absolutely none of these people can legitimately claim to be able to refute the article's statement based on personal experience - because all of them failed to fulfill an extremely simple condition within the statement. You are left with very few anecdotes now, generally with rather questionable validity. Good luck refuting the statement with the remaining candidates. Of course all of these were always completely worthless anyways because they're just anecdotes and fail miserably as a source at complying with [[WP:MEDRS]], but maybe now you have a better idea of why this statement is considered accurate. [[User:Garzfoth|Garzfoth]] ([[User talk:Garzfoth|talk]]) 02:39, 30 December 2016 (UTC)


My opinion, but shared by many researchers. Pharmacology for ADHD drugs are based on short term studies in young and adolescent children to establish therapeutic efficiency, short term side effects profile, and therapeutic dosage range.
:::::: {{Ping|86.153.54.114}} I'm aware that amphetamine pharmaceuticals in general are prescribed worldwide. Garzfoth is correct that the prescription of Adderall is limited to North America. I also know that 60 mg of Adderall is routinely recommended as a maximum dose in adults and that a weight-based dosing method is often used by doctors/psychiatrists to compute a dose to prescribe to patients. The maximum dose and the weight-based dosing method were both borne out of data derived from randomized controlled trials (RCTs). Similarly, my statement about long-term use of this drug at therapeutic doses not producing psychostimulant addiction is also borne out of data derived from longer-term RCTs (e.g., those with a duration of over 6 months) involving the treatment of narcolepsy or ADHD with amphetamine. It is possible to get addicted to amphetamine if a doctor prescribes a high dose of amphetamine via oral and particularly via an injectable route (e.g., the intravenous administration of '''≫'''&nbsp;80 mg/day of liquid dextroamphetamine from ampoules for the treatment of narcolepsy would likely produce an addiction after a few months of treatment; this dosage form for this condition is prescribed in the UK). In any event, if a doctor/psychiatrist chooses to prescribe more than is recommended (i.e., a supratherapeutic dose) by governmental regulatory agencies (e.g., the USFDA) or the drug manufacturers (via their [[prescribing information]], which the prescribing physician would have to read), the onus is on the clinician that prescribes amphetamine in such a manner to prevent the development of addiction in their patient. Consequently, I'm comfortable with this article making assertions relative to the term "therapeutic dose" because that dosage range is not specific to certain countries; it's derived from evidence-based medicine.<br />More relevant to actual WP content policy, the sources which support statements which include that term also directly support those statements, so there's no issue with [[WP:V|verifiability]].
Performed and paid for by drug companies to pass FDA approval to make money selling their product. These are reflected as the guidelines in the DSM-V as well as psychiatrist and neurologist curriculum. Which includes the drug companies taking points framing the narrative to their benefit. Adult dosage range was assumed from child studies. Research in adults just showed effect for the existing adolescents dosage range. None of these account for the dynamic therapeutic dosage range caused by tolerance. There is plenty of funding from big pharma for things in their interest. But a lack of funding for things that go against their narratives.
::::::Re: your claim about NPOV, these two sources - [http://www.recoveryanswers.org/blogs/adderall/] and [https://www.minnpost.com/second-opinion/2016/09/overprescribing-drugs-adult-adhd-causing-trail-misuse-addiction-and-death] - don't satisfy [[WP:MEDRS]] (or even [[WP:RS]] for that matter); [[WP:MEDRS]] is the wikipedia policy that covers the type of references that can be cited to support article statements which include medical claims. If you read that policy and can point me to a reliable medical source which supports the claim that you're making, I'm more than willing to include a statement in the article about that. At the moment, I know of no medical sources which make a claim like "The use of amphetamine for the treatment of ADHD has produced an addiction in some individuals when it was taken as prescribed". Also, the under- and over-prescription of psychostimulants, including amphetamine, for the treatment of ADHD is already covered in the ADHD article. This type of claim is more appropriate for that article since amphetamine pharmaceuticals, including Adderall, are also medically indicated for conditions other than ADHD.
If someone gets bored, they can compare the approved accompanying literature changes between releases and see how lacking info was till more recently. Which is still very lacking. Even some contradictions between Adderall and Adderall XR if you've read the XR design article
::::::I don't see anything that reads like a "disclaimer" in the side effects section. Can you be more specific? [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 18:48, 30 December 2016 (UTC)
:::::::::::On a completely off-topic note, it amuses me that [https://www.minnpost.com/second-opinion/2016/09/overprescribing-drugs-adult-adhd-causing-trail-misuse-addiction-and-death the author of this article] used [[COMMONS:File:Amph_salts.jpg|the image that I uploaded to commons]]. {{P|7}} [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 17:28, 30 December 2016 (UTC)
::::::::::::Hey look, it's ''that'' horrifically disgusting generic formulation! Is it just me or is that pill almost gag-inducing to take? I'm on it QID and I'm very tempted to beg my pharmacist to switch generics, I cannot tolerate the sickly-sweet nastiness when it starts to dissolve as you swallow it (and god forbid you don't swallow it the second it's in your mouth!). [[User:Garzfoth|Garzfoth]] ([[User talk:Garzfoth|talk]]) 20:49, 30 December 2016 (UTC)
::::::::::::Also, I've found several sources using my image of propranolol tablets [[COMMONS:File:Propranolol_tablets.png]] - it's always nice to see it being reused, even if a few of the sources are using it in entirely the wrong context (at least they all seem to properly attribute it to me/Wikimedia Commons). That picture was not easy to take with the equipment I used, and required a lot of work in photoshop to eliminate imperfections (although ironically the result of the work in photoshop was closer to reality than the original image). [[User:Garzfoth|Garzfoth]] ([[User talk:Garzfoth|talk]]) 21:12, 30 December 2016 (UTC)
:::::::::::::Yes, the taste sometimes makes me cringe if it dissolves in my mouth. [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 20:02, 1 January 2017 (UTC)
:::::::Holy crap, they prescribe d-amp injections of that size in the UK? What the hell are the doctors there smoking? It doesn't even make sense to inject d-amp for narcolepsy in the first place, you'd want an oral form...
:::::::I want to clarify that if the doctor prescribes a supratherapeutic dosage (which is fairly rare), it's an exception made based on that clinician's judgement call that this (off-label) dosage of the drug is necessary for optimal treatment of the patient's condition and that the clinician has assessed the risk-benefit equation of a supratherapeutic dosage in this particular case and determined it to be positive. I thought that simplifying the description the way you did wasn't quite clear enough.
:::::::I do feel the need to point out that the specific "maximum dosage" for psychostimulants ''does'' vary to a small extent depending on the country, but that these differences are minimal. By the way, the maximum dosage is generally not determined by evidence-based medicine in the case of psychostimulants, it is an arbitrary limit based on what the regulatory agency will approve (which is only in part based on evidence from clinical trials and involves a few too many overly-cautious and highly subjective judgement calls). I have a MEDRS-compliant ref somewhere that explicitly supports this for at least one psychostimulant if you want me to cite that claim. [[User:Garzfoth|Garzfoth]] ([[User talk:Garzfoth|talk]]) 21:06, 30 December 2016 (UTC)
::::::::{{tq|they prescribe d-amp injections of that size in the UK}} - no, I was stating that as an example of an excessive daily dose that a doctor ''could'' prescribe, not a dose that doctors typically prescribe. <br />The maximum recommended dose for amphetamine pharmaceuticals isn't arbitrary; it's based upon clinical trials that examine differences in treatment efficacy of amphetamine for ADHD when it is administered at different doses. In most people, the treatment efficacy for ADHD plateaus beyond a certain dose - that particular dose varies by formulation. [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 20:02, 1 January 2017 (UTC)
:::::::::As far as I can tell dextroamphetamine ampoules aren't available in the UK. If you wanted to use it as an example, you should have used a plausible one - I don't think there is a single reason to ever prescribe >> 80mg injectable doses of dextroamphetamine daily (assuming it's even possible to acquire the injectable form anywhere in the world - as far as I know only research studies have ever been allowed to acquire and use injectable forms of common stimulants), as it's all but guaranteed to end very very ''very'' poorly. A more plausible excessive daily dose that's relevant to this article is 120mg daily of MAS/Adderall, taken orally in divided doses - this is a very high dose, but it's actually a plausible one (although it's quite rare to see).
:::::::::Amphetamines are actually a unique case, as both Dexedrine and Adderall have excessively vague dosing guidelines in product monographs. Both monographs both only discuss pediatric dosing - adult dosing is not discussed at all (and Dexedrine in particular actually explicitly says that the indications are for pediatric patients up to 16 years old). For pediatric ADHD, it states that dosage should be increased until an optimal response is obtained, and that "only in rare cases will it be '''necessary to exceed''' a total of 40 mg per day". For pediatric narcolepsy, it states "'''usual dose''' [is] 5 mg to 60 mg per day in divided doses, depending on the individual patient response" (the "is" in this quote only appears in the Dexedrine monograph). '''''Neither condition-specific dosing guideline in the product monograph for the two most important amphetamine formulations specifies an actual maximum dosage.''''' In contrast, Ritalin's monograph mentions adults (although I think this is solely because it only exists as a combined monograph for Ritalin SR and Ritalin IR), and while it is less vague about adult dosage maximums (only saying that "''some patients may require 40 to 60 mg'' daily"), it's not perfectly clear until you come to the child dosing guidelines, which state "daily dosage ''above 60 mg is not recommended''". Even the more modern products are still vague in their product monographs - the only one that explicitly defines a maximum is Concerta (it explicitly says 72mg is the "maximum"), Aptensio says "Daily doses above 60 mg have not been studied and are not recommended" (even though it's false that doses above 60mg have not been studied and even the fucking product monograph contains numerous references to data involving the 80mg dose form, which is the maximum dose form approved in Canada where this product was originally marketed as Biphentin (which is actually really odd given Health Canada's approval of a max dose of 54mg for Concerta rather than 72mg, the lack of Adderall IR in Canada, that one massive mess with Adderall XR getting withdrawn temporarily, etc)), and I was ''extremely'' surprised to see that the Vyvanse monograph only says "the maximum recommended dose for children is 70 mg/day; doses greater than 70 mg/day of Vyvanse have not been studied in children" - the only other constraint on dosing is that it should be individualized to needs/response and should be administered at the lowest effective dosing - which isn't really a constraint.
:::::::::Now on the above, I know in particular that we have strong trial data supporting Concerta's efficacy at doses of up to 108mg/day, and that trial data on methylphenidate in general is mixed but does not support the arbitrary 60mg limit that is generally accepted and roughly defined in most product monographs. I dug up that paper on Methylphenidate dosing ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181133/]), and here's the quote:
::::::::::"While the dosage range varies for children, the average daily dose of methylphenidate for adults is 20 to 30 mg/day. Most texts recommend that the daily dose should not exceed 60 mg, although some individuals may require higher doses. '''''This limit of 60 mg/day appears to be arbitrary and not based on clinical research.''''' Studies for adults with ADHD suggest 1 mg/kg/day as the usual dose with lower doses producing less response. These dosages refer to the therapeutic oral dose."
:::::::::Here's a relevant quote from a completely different paper ({{pubmed|14594733}}) that quantifies typical responses (and is a really good paper in general): "[...]the requirement for very high doses to produce clinical effects, which is required in about 20% of those who are considered responsive to stimulants"
:::::::::I don't want to undermine your argument too much, because its core is completely valid, but the idea that we have strongly evidence-based maximum doses for psychostimulants in use today is pure baloney. There's a reason why these monographs all emphasize titrating to effect first and foremost, why professional guidelines from groups like CADDRA and a major narcolepsy-related organization strongly emphasize this much further while uniformly and often drastically redefining maximum dosages, why clinical practice involves as many as 20% of patients taking doses beyond monograph limits, why scientific data disagrees so strongly with the generally-accepted guidelines for methylphenidate, why so many psychiatric professionals with sizable amounts of actual experience prescribing psychostimulants disagree with the "generally accepted typical guidelines", etc... Unfortunately this is a case where too many pieces of the puzzle are disconnected from each other and nobody really cares enough about clarifying incorrect information since it usually doesn't affect the people that know it's wrong.
:::::::::Really, it'd be better to say this about psychostimulants: addiction potential is only a serious concern if the drug is being misused in some way, as opposed to being taken as prescribed. If you're taking it by ANY non-oral route (or non-transdermal in the case of Daytrana) - you are misusing it, and it's much more addictive (nasal is very bad, rectal is extremely bad, IV is game-over). If you're taking more than prescribed in ANY way (more doses per day, multiple doses at once, time between doses too short, defeating the time-release mechanism via crushing/chewing/etc to turn an XR pill into IR) - you are misusing it, and it's much more addictive (although the magnitude varies based on what you're doing). If you combine taking it via the wrong route with taking more than prescribed, you are practically guaranteed addiction. I didn't mention a few Daytrana-specific misuse signs, but I'll go over them quickly - attempting to artificially increase the rate of release from the patch by ANY means, leaving it on longer than the maximum allowable time (9 hours?), attempting to use it orally (or via any other non-transdermal method), and of course the other non-specific misuse signs still apply alone and in combination with these and others.
:::::::::Psychostimulants should of course always be prescribed at the lowest effective dose, but that's very different from a "low dose", and even a low dose can easily be misused and lead to addiction. We don't have enough evidence to actually say if someone who requires a high dose is actually at a significantly higher risk for addiction (and I honestly don't even know how strong the data is on accidental overmedication past the effective dose as a factor in addiction risk - it's definitely very bad practice, but the addiction-specific risk isn't clearly known past the knowledge about too-strong effects being generally linked to increased drug liking). Part of the reason the "generally accepted typical guidelines for maximum doses" are low is because of the desire to avoid overmedication in general, but it's a knee-jerk response to that issue that fails to solve anything (if someone would respond well to 10mg/day but you prescribe them 20mg/day because the product monograph says that's an okay dose and you're too stupid to follow the titration guidelines properly, that person is going to have similar issues to someone who responds to 40mg/day but ends up with 80mg/day - the only difference is that skipping titration completely will make things temporarily nastier with higher doses for the first few days mostly irregardless of your personal "response dosage", but that's a minor factor). That's an extreme example too, it's more common to see people titrated normally with a subsequent failure to wrap up titration correctly when the therapeutic response is achieved, so the target is overshot and stays that way. It can be argued that a higher max dose makes doctors more comfortable titrating to higher doses, but that's not necessarily a bad thing at all (if they're titrating like they're supposed to, this is a good thing, and it helps address undertreatment - which is a pretty significant issue - and a surprisingly large amount of doctors are ignorant about psychostimulant treatment in weird ways, like having personal definitions of the maximum dose that's far below even the monograph doses, or not understanding a LOT of basic dosing concepts for psychostimulants in general that any prescriber should understand before prescribing this type of drug).
:::::::::ANYWAYS, while this is a fascinating subject to discuss, I really need to wrap this up. I think I've addressed everything, keep in mind that the dosage plateau follows the "target" or "response" dosage (just making sure the terms I used are in concordance), and if it's not clear enough already, I'll repeat it again: the target/response dosage and thus the location of the start of a dosage plateau is COMPLETELY individualized and fluctuates WILDLY, setting an arbitrary maximum dose that flat-out cuts off ~20% of medication responders is extremely harmful (leading to extremely suboptimal treatment for that ~20% at absolute best, but usually to mistakenly perceived nonresponse, plus some level of suboptimal treatment for a significant portion of responders). [[User:Garzfoth|Garzfoth]] ([[User talk:Garzfoth|talk]]) 20:34, 2 January 2017 (UTC)
::::::::::I don't disagree with what you said. What you've stated and quoted (e.g., {{tq|clinical practice involves as many as '''20% of patients''' taking doses beyond monograph limits}}) is entirely consistent with what I've claimed ({{tq|'''In most people''', the treatment efficacy for ADHD plateaus beyond a certain dose}}); a corollary to my statement is: "in a minority of people, treatment efficacy dose not plateau beyond the same dose at which it does in the majority".
::::::::::In any event, I strongly disagree with that reference's claim that these recommended limits are arbitrary and not based upon clinical research; regulatory agencies like the FDA don't make "arbitrary" decisions when it comes to dosing information; just imagine how much that practice could fuck people who take a drug with a narrow [[therapeutic index]]. More than likely, the maximum recommended dose is the largest dose that has been used in clinical trials of a sufficient size. The selection of that "largest dose" by the trial coordinators likely was arbitrary; but, the selection of the same dose as the maximum recommended dose by manufacturers/regulatory agencies is not precisely because it is based upon what has been used in the available clinical research. Nonetheless, the maximum recommended doses for ADHD drugs are simply recommendations and not actual prescribing limits since, as you've pointed out, exceptions occur in clinical practice where efficacy improves at higher doses which are still tolerable to the patients. [[User:Seppi333|'''<font color="#32CD32">Seppi</font>''<font color="Black">333</font>''''']]&nbsp;([[User Talk:Seppi333|Insert&nbsp;'''2¢''']]) 21:30, 2 January 2017 (UTC)
:::::::::::Fair enough, although I'll make a point related to this at the end of my message... Now for the rest:
:::::::::::Limits can easily be arbitrarily determined without fucking people over (at least not in terms of drug toxicity - efficacy is another matter) when the drug has a very very wide therapeutic index. You're also using an extremely absolute interpretation of the term arbitrary - arbitrary is defined as "subject to individual will or judgment without restriction; contingent solely upon one's discretion", this does not mean that an arbitrary decision is by nature utterly irrational and random, just that one has a great deal of choice in how to decide the result and that they are completely free to ignore external rationale/information to whatever extent they desire.
:::::::::::Now, Ritalin was approved by the FDA on Dec 5th 1955. I have no clue if there even ''was'' a product monograph back then, nor do I know exactly when it was first published, but in theory it was published by 1981 at the latest according to the FDA's rather frustratingly flawed records. I have no clue if any clinical trial data ever went into this drug's dosage limit. However, a closer examination of the monograph reveals that there are two maximum dosages listed - the maximum daily dose of 60mg, and a "do not exceed" dose of 2mg/kg. The "do not exceed" dose appears to be a relic of pediatric weight-based dosing with some limited grounding in clinical trial data, while the maximum daily dose has no grounding in clinical trial data.
:::::::::::But I want to prove a different point. Let's look at Concerta, another methylphenidate-based drug. This was originally tested in clinical trials at doses of up to 54mg/day and was approved for doses of up to 54mg/day. However in 2004 the drug's indication was revised to reflect an increase in the maximum dosage to 72mg, making it the only methylphenidate product in the history of the FDA (and there have been many!) to receive an approval for a maximum dosage beyond (and not equal to) 60mg. One may argue that this is solely because the company introduced new clinical trial data to support this new dosage level, which would make sense at first glance. Yet in 2008 when Concerta's indication was revised again to include an adult indication, the dosage limit remained the same despite new trial data being included that spanned a dosage range of 18mg-108mg. Over time, a number of trials conducted for reasons related to FDA approval were subsequently published in the scientific literature. A 5-week randomized fixed-dose study assessed the results of 18-72mg doses, but produced mixed data in some areas due to the fixed-dose component. A 7-week open-label extension of this trial assessed a dosage range of 18-90mg with favorable results. A 7-week randomized dose-escalation trial spanned a dosage range of 36-108mg, with results that strongly supported approval of 90mg-108mg dose limits. These trials appear to have all been assessed by the FDA at the time of the approval of Concerta for adults with ADHD. Despite strong scientific evidence, similar or greater in quality to the evidence used to approve the previous adolescent dose increase to 72mg, the FDA only approved a maximum dosage of 72mg in adults. A minimum of 90mg would have been warranted given the evidence at their disposal. To add insult to injury, a ''one-year'' open-label extension of the initially-randomized 7-week dose-escalation trial produced results that were in concordance with the previous two >72mg trials and very firmly proved that sufficient clinical trial data existed to approve a limit of 90mg-108mg. The data did not just prove that these high dosages were safe and effective - it also proved that a significant portion of responders ended up at these dosages. This goes above and beyond the FDA's requirements. Yet the higher dosage forms were never approved.
:::::::::::Similarly strong proof of the FDA's bias against approving higher dosage forms of methylphenidate-based drugs despite strong clinical trial evidence can be found in the case of Biphentin (rebranded as Aptensio for the US market). Biphentin is a methylphenidate-based extended-release drug that has been marketed in Canada for some time now. It was approved in Canada at dosages of up to 80mg, despite Canada using the original 54mg maximum dosage in their Concerta monograph (while acknowledging in that same monograph that studies covered up to 72mg in adolescents and up to 90mg in adults - although oddly enough they omitted the fact that up to 108mg in adults was covered, and seem to have decided that they don't want to approve higher dosages in either adolescents or adults despite the evidence and FDA approval). Quite a lot of data exists to support Biphentin's safety and efficacy in dosages of up to 80mg per day. A document on the FDA site related to the drug application for Aptensio contains redacted mentions of what can only be the 80mg dosage form, indicating that the 80mg dosage form was part of the application to the FDA - and they rejected it, despite a foreign approval, years of successful use, and a avalanche of supporting data. Yet ironically, the Aptensio product monograph contains numerous mentions of the 80mg dose form in study data while simultaneously claiming that dosage forms beyond 60mg were never evaluated! The FDA didn't even bother trying to say that 60mg was the max dose (which would at least stop some of their hypocrisy), but no, they decided to lie and say that it was the maximum dosage evaluated despite the data in the monograph contradicting this!
:::::::::::So there's two major examples of some solid proof that the FDA doesn't give a shit about your trial data when it comes to methylphenidate (and likely other psychostimulants), and another example from a different regulatory authority (Health Canada) that did similar things with Concerta. As this shows, the decisions of these regulatory agencies are arbitrary. If they were based in fact, they would conform to the evidence - which they do not!
:::::::::::So again I need to wrap things up. The idea that this is just a "suggestion" is a problem, because like I said, a LOT of doctors don't understand how to RX psychostimulants, and if you don't know how to RX psychostimulants, you're going to follow the monograph. And the uncertainty in the product monographs as a whole with regards to maximum dosage contrasted against how people view maximum dosage as a much more rigid thing (as well as the non-uniformity everywhere) proves that there is a serious problem here. So, well, none of this shit is okay. Btw empirical data in the Concerta trials shows that ''well'' over 20% (like closer to twice that) require higher-than-US-monograph-maximum doses for optimal response, so exact numbers aren't necessarily just 20% (this might reflect partially impacted + fully impacted users), but even if it's actually just 20%, that's still 20% of responders that you are throwing away for no good reason. 20% isn't fringe cases only, it's one in five people, that's a LOT. [[User:Garzfoth|Garzfoth]] ([[User talk:Garzfoth|talk]]) 00:15, 3 January 2017 (UTC)


[[User:HCStymie|HCStymie]] ([[User talk:HCStymie|talk]]) 21:58, 5 August 2024 (UTC)
== Footnotes ==


:1. Can you reword your concerns as bullet point sentences instead of paragraphs? It's quite difficult to understand what content you believe violates policy a la [[Wikipedia:Neutral point of view|WP:NPOV]].
I like the way the footnotes are organized in this article, keeping the clutter out of the article. [[User:Permstrump|<font color="indigo">—'''PermStrump'''</font>]][[User Talk:Permstrump|<font color="steelblue">(<u>talk</u>)</font>]] 19:03, 30 December 2016 (UTC)
:2. If/when rewording your concerns as bullet point sentences, can you also quote specific excerpts from the article that you believe violate policy?
:Thanks. [[User:Professional Crastination|Professional Crastination]] ([[User talk:Professional Crastination|talk]]) 12:38, 6 August 2024 (UTC)
::I will try but won't be for quite a while as I am recovering from long term damage caused by prescription Adderall. [[Special:Contributions/2601:8C:4E80:7578:6138:2331:E1B3:6E99|2601:8C:4E80:7578:6138:2331:E1B3:6E99]] ([[User talk:2601:8C:4E80:7578:6138:2331:E1B3:6E99|talk]]) 12:07, 13 November 2024 (UTC)
::Forgot to mention, a few answers are in the actual FDA approved prescriber documentation for Adderall. This is an annoying cut and past of some notes but it is one step further. Shows toxic even at low doses, not just abused! Shows some endocrine effects and adverse reactions, again, at prescribed and even low doses. Other good documentation in the history like never established an adult dosage range, just allowed doctors to assume it etc. Also, mentions there are no long term studies which shows guidelines are from short term studies done in children. More info I didn't cover from FDA docs that is relevant to the page. Similar with Adderall XR docs where it actually contradicts some Adderall docs info unless person knows underlying context.
::Official FDA approved label for adderall with excerpts
::2024
::https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f22635fe-821d-4cde-aa12-419f8b53db81&type=display
::Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening.
::—--
::ADVERSE REACTIONS
::Central Nervous System
::Psychotic episodes at recommended doses, overstimulation, restlessness, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, motor and verbal tics, aggression, anger, logorrhea, dermatillomania.
::Gastrointestinal
::intestinal ischemia, and other gastrointestinal disturbances.
::Endocrine
::Impotence, changes in libido, frequent or prolonged erections.
::Skin
::Alopecia.
::Musculoskeletal
::Rhabdomyolysis.
::—-------
::Dependence
::Physical Dependence
::Adderall® may produce physical dependence. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.
::Withdrawal signs and symptoms after abrupt discontinuation or dose reduction following prolonged use of CNS stimulants including Adderall® include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.
::Tolerance
::Adderall® may produce tolerance. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
::—------------------------------------------------------------------------------------
::https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=011522
::From 2017 documentation: No mention of adult dosing or indication for adult disorders.
::Long-Term Use
::The effectiveness of Adderall® for long-term use has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use Adderall® for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
::2007
::OVERDOSAGE: Individual patient response to amphetamines varies widely. Toxic symptoms may occur idiosyncratically at low doses. Symptoms:
::From 2005
::Drug/Laboratory Test Interactions:
::• Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening.
::ADVERSE REACTIONS
::Endocrine:
::Impotence, changes in libido.
::OVERDOSAGE:
::Individual patient response to amphetamines varies widely. While toxic symptoms occasionally occur as an idiosyncrasy at doses as low as 2 mg, they are rare with doses of less than 15 mg; 30 mg can produce severe reactions, yet doses of 400 to 500 mg are not necessarily fatal.
::—-------
::FDA doc mentions high corticosteroids from Adderall. Here are symptoms of chronically high cortisol which would also be side effects caused by Adderall.
::https://www.google.com/search?q=side+effects+of+high+cortisol&rlz=1CADRLH_enUS1010&oq=side+effects+of+high+cortisol&gs_lcrp=EgZjaHJvbWUyBggAEEUYOdIBCDcyOTNqMGo3qAIAsAIA&sourceid=chrome&ie=UTF-8
::Here is a list of chronically high cortisol symptoms.
::–Brain fog: Difficulty concentrating, focusing, and a slower thought process
::–Sleep disturbance: Lack of energy
::–Decreased libido: Cortisol suppresses sex hormones and decreases testosterone
::–Weight gain: Especially in the face and abdomen, and sometimes with a rounded face
::–High blood pressure: Also known as hypertension
::–High blood sugar: Which can lead to type 2 diabetes
::–Fatty deposits: Between the shoulder blades
::–Stretch marks: Wide, purple stretch marks on the abdomen
::–Muscle weakness: In the upper arms and thighs
::–Bone loss: Also known as osteoporosis, which can lead to fractures
::–Susceptibility to infection: Cortisol can impair the immune system
::–Heart palpitations: A racing heart
::–Restlessness: Anxiety
::–Constipation: Feeling bloated
::–Headaches: [[Special:Contributions/2601:8C:4E80:7578:6138:2331:E1B3:6E99|2601:8C:4E80:7578:6138:2331:E1B3:6E99]] ([[User talk:2601:8C:4E80:7578:6138:2331:E1B3:6E99|talk]]) 12:39, 13 November 2024 (UTC)
:::I'm still not sure what you want changed in the article/what specifically violates [[Wikipedia:Neutral point of view|WP:NPOV]]. I requested bullet point sentences and quoted examples of WP:NPOV violations, but instead you've essentially source dumped the USFDA prescribing info - which is already covered extensively in [[Adderall#Adverse effects]] (NB: much of that section is transcluded from [[Amphetamine#Adverse effects]] and happens to be [[Featured article (English Wikipedia)|featured article]] compliant) - and supplied a google search URL for "side effects of high cortisol", which isn't a [[Wikipedia:Identifying reliable sources (medicine)|MEDRS]] citation, let alone a citation that discusses side effects of pharmaceutical ''amphetamine''. [[User:Professional Crastination|Professional Crastination]] ([[User talk:Professional Crastination|talk]]) 08:48, 2 December 2024 (UTC)


== External links modified ==
== MAS title usage ==


@[[User:Gobucks821|Gobucks821]] I've reverted [https://en.wikipedia.org/enwiki/w/index.php?title=Adderall&diff=prev&oldid=1231123375 the changes you made] Re: {{tq|substituting Adderall for "MAS products" throughout the article}}.
Hello fellow Wikipedians,


Adderall is the title of this article and the usage of Adderall to refer to the specific amphetamine salt composition in both Adderall and Mydayis dosage formulations is underpinned [[Talk:Adderall/Archive 4#Changing Title Back to "Amphetamine Mixed Salts"|by previous consensus on this article's talk page]]. Moreover, the [https://en.wikipedia.org/enwiki/w/index.php?title=Adderall&oldid=1234553847#cite_note-Adderall-13 note in the title sentence of this article] clarifies the usage of Adderall throughout the article.
I have just modified one external link on [[Adderall]]. Please take a moment to review [https://en.wikipedia.org/enwiki/w/index.php?diff=prev&oldid=779254594 my edit]. If you have any questions, or need the bot to ignore the links, or the page altogether, please visit [[User:Cyberpower678/FaQs#InternetArchiveBot|this simple FaQ]] for additional information. I made the following changes:
*Added archive https://web.archive.org/web/20140308001155/http://narcotic.fda.moph.go.th/faq/upload/Thai%20Narcotic%20Act%202012.doc._37ef.pdf to http://narcotic.fda.moph.go.th/faq/upload/Thai%20Narcotic%20Act%202012.doc._37ef.pdf


For those reasons, in future you need to gain consensus on this article's talk page before making a change like that. [[User:Professional Crastination|Professional Crastination]] ([[User talk:Professional Crastination|talk]]) 05:02, 7 August 2024 (UTC)
When you have finished reviewing my changes, you may follow the instructions on the template below to fix any issues with the URLs.


==Contra TAAR1 agonism as the mediator of amphetamine actions==
{{sourcecheck|checked=true}}
Requesting input on this topic [[Wikipedia_talk:WikiProject_Pharmacology#Contra_TAAR1_agonism_as_the_mediator_of_amphetamine_actions|here]] at WikiProject Pharmacology. Thanks. – [[User:AlyInWikiWonderland|AlyInWikiWonderland]] ([[User_talk:AlyInWikiWonderland|talk]], [[Special:Contributions/AlyInWikiWonderland|contribs]]) 16:00, 13 December 2024 (UTC)

Cheers.—[[User:InternetArchiveBot|'''<span style="color:darkgrey;font-family:monospace">InternetArchiveBot</span>''']] <span style="color:green;font-family:Rockwell">([[User talk:InternetArchiveBot|Report bug]])</span> 21:59, 7 May 2017 (UTC)

== Salt/enantiomer composition ==

Hi - organic chemist here. I don't want to make an edit in case I'm missing something here (I'm not necessarily familiar with pharmacological conventions), but it seems a little silly to me to include both this

:''amphetamine sulfate''
:''25% - stimulant''
:''(12.5% levo; 12.5% dextro)''

and this

:''dextroamphetamine sulfate
:''25% - stimulant''
:''(0% levo; 25% dextro)''.

Rather than taking out the latter altogether and changing the former to

:''amphetamine sulfate''
:''50% - stimulant''
:''(12.5% levo; 37.5% dextro)''.

Another alternative would be to list the ''levo'' and ''dextro'' enantiomers separately, but the aforementioned suggestion seems to follow the convention used for the aspartate salt. --[[Special:Contributions/129.10.29.29|129.10.29.29]] ([[User talk:129.10.29.29|talk]]) 00:16, 14 March 2018 (UTC)

== Generic term for Adderall? ==

Evening all. Just wondering if there is a shorter generic term for Adderall (so that there is not the need to use a proprietary brand name to refer to the compound? Perhaps Amphetamine-dextroamphetamine? Not being a chemist or a doctor not sure if this would be appropriate at all. [[User:Thunderstorm008|Thunderstorm008]] <span style="font-size:85%;">([[User talk:Thunderstorm008|talk]] &middot; [[Special:Contributions/Thunderstorm008|contributions]])</span> 17:03, 5 September 2018 (UTC)

Revision as of 09:12, 14 December 2024

Good articleAdderall has been listed as one of the Natural sciences good articles under the good article criteria. If you can improve it further, please do so. If it no longer meets these criteria, you can reassess it.
Article milestones
DateProcessResult
December 3, 2014Good article nomineeListed


Shortages

Shortages section needs a lot of work. FDA actually first reported the shortage in I think may or june, then declared it to be over in I believe September. The actual shortage started back in 2021. There are references that mention that if people look hard enough.

It needs to be noted that shortages as reported by the FDA are based on voluntary reporting by manufacturers and is not required. And therefore do not accurately represent shortages as seen by consumers. If they choose not to report then it goes without being recognized by the FDA. So, when Teva waited till late spring I think of 2022 to bother to report their shortage, there was already a profound effect on users having issues getting their script filled and they got back lash for waiting too long. Also, manufactures tend to downplay the extent of the issue and underestimate the time to the shortage being over. All this is documented in articles if people look. I don't have the time to go back and dig every thing up again.

And if putting a shortages section. If people don't know when the other shortages were over the years, should at least mention that the most recent one is not the only one. I know there was one I believe in 2012 when I think Shire redirected the API to their Vyvanse instead of distributing it to the generic companies as they were contracted to. Causing the shortage.

There is a document in 2015 to congress from an investigation into the DEA noting all their shortcomings and failures in regards to their control of the amphetamine API and quota system from the 2012 shortage. Which can also show how they impacted and again exacerbated the current shortage.

There was at least 1 other shortage but not as bad between the 2012 and current one. Forget when it was exactly. So, I think the shortages section should be renamed to "Shortage 2021 to 2023" because "Shortages" implies more than one, and only 1 is listed skipping all the others, and the info is incorrect at that to begin with. Until someone feels like putting in effort for either title, it should be removed. 2601:86:600:A85:14B1:C34D:88DA:1EF1 (talk) 05:26, 16 May 2023 (UTC)[reply]

Please correct...

(1) Please correct the following appearing content to a scholarly understanding of molecular microbiology:

"Since the total number of microbial and viral cells..."

(2) Please do the same to the source of the content, in the referenced section of the Amphetamines article.

(3) More broadly, please consider whether this article needs such a long introductory paragraph as the one containing this sentence. The shorter following paragraph is indeed relevant to the article. In this editor's opinion, there is no need to spend as much time defining a field as presenting a specific result from it; the content giving explanatory and defining information (e.g., indicating numbers of microbial cells in the microbiome, etc.) is superfluous.

The entire first paragraph here could be replaced by one sentence with a wikilink and a citation or two (serving as an introductory sentence to the content of the current second paragraph). 73.8.193.28 (talk) 00:22, 3 December 2023 (UTC)[reply]

Insufflation

Why is insufflation listen as a method of administration of adderall in the sidebar? Themckinlay (talk) 13:52, 2 August 2024 (UTC)[reply]

Article is biased.

Article is very biased. Same rhetoric propagated all too often. Negative effects are in context of abuse. Adderall can cause the same issues at prescribed levels as at the abused levels, only slower. Always stating the negative in terms of abuse is a "blame the victim" narrative for anyone with issues at therapeutic doses. Even ICD10 and ICD11 codes for side effects from amphetamine states it can occur at therapeutic prescribed doses. Although the listed number of possible side effects is quite limiting. Research, especially in adults has shown this too.

I apologize for not having all the links for all these things as this is not being written on my computer.

Article mentions young children who start on Adderall are less likely to become addicts when they get older. What they fail to mention is that starting in adolescents or adulthood, people are more likely to become addicts as they are more willing to self medicate or seek a euphoric dose.

Missing is one of the primary effects of amphetamine is the AMPA/NMDA antagonism causing glutamate release. And believed by many researchers to be the primary way amphetamine builds tolerance.

Also lacking is many of the ways amphetamine causes downregulation and damage. --adderall can be exciteotoxic to the NMDA/glutamatergic pathways. Over excitement causes downregulation of receptors and excess ion flux causes oxidative stress in the cell that can lead to disregulation or even apoptosis. Excess glutamate triggers extrasynaptic NMDA receptors which is the trigger for the apoptosis cascade. Many researchers believe this to be the primary way amphetamine builds tolerance. And why some therapist prescribe the NMDA uncompetitive antagonist memantine to prevent or reduce tolerance. --Does mention the phosphorilization of DAT and NAT. But does not mention that this is acute tolerance and causes a need for a higher blood API concentration in the afternoon just to maintain the same therapeutic efficiency as the morning. And why the standard recommended dosage is the same dose separated by about 4 hours, which nearly doubles the BAC to maintain steady therapeutic effect and how Adderall XR was designed. I do have an article for the readily available. Shows acute tolerance, therapeutic dose curve during the day. But before they understood acute tolerance is from phosphorilization of DAT and NAT and likely other pathways like NMDA. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2547091/ --VMAT2 can get downregulated or cause dysfunction. --Amphetamine can diffuse through the cell wall, doesn't just use DAT or NAT transports. And can diffuse through mitochondria wall which it can cause oxidative stress in mitochondria. --Can't recall if MOA antagonism was mentioned, but it can cause damage or downregulation too. --A lot of the catecholamines get stuck in the cytosol which auto-oxidizes leading to oxidative stress. As does excess in the synapse and extra-synaptic space. --Does regulation of tyrosine hydroxylase has been shown can happen with long term use. --A know there are other neurological factors I don't recall.

Endocrine side effects was not even mentioned. Less research but it does exist. Even the FDA approved accompanying literature mentions endocrine effects but very lacking in longer term effects. --A THE and cortisol decrease during the day. amphetamine has the opposite effect on it. --Can cause testosterone/estrogen imbalance in part due to weak estrogenic property of amphetamine. But likely due to other reasons too. Which in men has low T symptoms. --Can decrease LH and FSH which can effect fertility. --Can cause stimulant induced secondary gynecomastia. Which can be distinguished from other forms of gynecomastia by stimulant use, estrogen dominance, normal or low levels of LH and FSH. --Can increase cAMP, which I don't recall for sure but may have been a side effect of high ACTH. --There are some others I forget off the top of my head.

Only references an article in which it states higher dose users can take up to 4 weeks to recover from stopping medication. Doesn't mention that is not true for everyone and although not frequent, some people can take 6 months to a year, even from prescribed high doses. Has been shown in other studies that even at low doses there is a significant number of patients who show accumulated tolerance and stopping medication worsens ADHD symptoms for a while. Amphetamine can also cause irreversible damage for some people while addicts can also often make a full recovery.

There is some study on how adults respond differently to the medication, especially in the long run. But also acknowledge adult research is still lacking in many ways.

Many studies on CNS stimulants stunting growth say on stopping medication, growth resumes and is unaffected. While other studies show a decrease final height even after stopping medication that is statistically significant compared to placebo group. Think on average it may have been a 1/2 inch shorter but not sure. Don't recall reading studies on children who stayed on longer after stunted growth was recognized. Which doesn't mention the underlying cause but likely something in the endocrine system.

My opinion, but shared by many researchers. Pharmacology for ADHD drugs are based on short term studies in young and adolescent children to establish therapeutic efficiency, short term side effects profile, and therapeutic dosage range. Performed and paid for by drug companies to pass FDA approval to make money selling their product. These are reflected as the guidelines in the DSM-V as well as psychiatrist and neurologist curriculum. Which includes the drug companies taking points framing the narrative to their benefit. Adult dosage range was assumed from child studies. Research in adults just showed effect for the existing adolescents dosage range. None of these account for the dynamic therapeutic dosage range caused by tolerance. There is plenty of funding from big pharma for things in their interest. But a lack of funding for things that go against their narratives. If someone gets bored, they can compare the approved accompanying literature changes between releases and see how lacking info was till more recently. Which is still very lacking. Even some contradictions between Adderall and Adderall XR if you've read the XR design article

HCStymie (talk) 21:58, 5 August 2024 (UTC)[reply]

1. Can you reword your concerns as bullet point sentences instead of paragraphs? It's quite difficult to understand what content you believe violates policy a la WP:NPOV.
2. If/when rewording your concerns as bullet point sentences, can you also quote specific excerpts from the article that you believe violate policy?
Thanks. Professional Crastination (talk) 12:38, 6 August 2024 (UTC)[reply]
I will try but won't be for quite a while as I am recovering from long term damage caused by prescription Adderall. 2601:8C:4E80:7578:6138:2331:E1B3:6E99 (talk) 12:07, 13 November 2024 (UTC)[reply]
Forgot to mention, a few answers are in the actual FDA approved prescriber documentation for Adderall. This is an annoying cut and past of some notes but it is one step further. Shows toxic even at low doses, not just abused! Shows some endocrine effects and adverse reactions, again, at prescribed and even low doses. Other good documentation in the history like never established an adult dosage range, just allowed doctors to assume it etc. Also, mentions there are no long term studies which shows guidelines are from short term studies done in children. More info I didn't cover from FDA docs that is relevant to the page. Similar with Adderall XR docs where it actually contradicts some Adderall docs info unless person knows underlying context.
Official FDA approved label for adderall with excerpts
2024
https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f22635fe-821d-4cde-aa12-419f8b53db81&type=display
Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening.
—--
ADVERSE REACTIONS
Central Nervous System
Psychotic episodes at recommended doses, overstimulation, restlessness, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, motor and verbal tics, aggression, anger, logorrhea, dermatillomania.
Gastrointestinal
intestinal ischemia, and other gastrointestinal disturbances.
Endocrine
Impotence, changes in libido, frequent or prolonged erections.
Skin
Alopecia.
Musculoskeletal
Rhabdomyolysis.
—-------
Dependence
Physical Dependence
Adderall® may produce physical dependence. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.
Withdrawal signs and symptoms after abrupt discontinuation or dose reduction following prolonged use of CNS stimulants including Adderall® include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.
Tolerance
Adderall® may produce tolerance. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
—------------------------------------------------------------------------------------
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=011522
From 2017 documentation: No mention of adult dosing or indication for adult disorders.
Long-Term Use
The effectiveness of Adderall® for long-term use has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use Adderall® for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
2007
OVERDOSAGE: Individual patient response to amphetamines varies widely. Toxic symptoms may occur idiosyncratically at low doses. Symptoms:
From 2005
Drug/Laboratory Test Interactions:
• Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening.
ADVERSE REACTIONS
Endocrine:
Impotence, changes in libido.
OVERDOSAGE:
Individual patient response to amphetamines varies widely. While toxic symptoms occasionally occur as an idiosyncrasy at doses as low as 2 mg, they are rare with doses of less than 15 mg; 30 mg can produce severe reactions, yet doses of 400 to 500 mg are not necessarily fatal.
—-------
FDA doc mentions high corticosteroids from Adderall. Here are symptoms of chronically high cortisol which would also be side effects caused by Adderall.
https://www.google.com/search?q=side+effects+of+high+cortisol&rlz=1CADRLH_enUS1010&oq=side+effects+of+high+cortisol&gs_lcrp=EgZjaHJvbWUyBggAEEUYOdIBCDcyOTNqMGo3qAIAsAIA&sourceid=chrome&ie=UTF-8
Here is a list of chronically high cortisol symptoms.
–Brain fog: Difficulty concentrating, focusing, and a slower thought process
–Sleep disturbance: Lack of energy
–Decreased libido: Cortisol suppresses sex hormones and decreases testosterone
–Weight gain: Especially in the face and abdomen, and sometimes with a rounded face
–High blood pressure: Also known as hypertension
–High blood sugar: Which can lead to type 2 diabetes
–Fatty deposits: Between the shoulder blades
–Stretch marks: Wide, purple stretch marks on the abdomen
–Muscle weakness: In the upper arms and thighs
–Bone loss: Also known as osteoporosis, which can lead to fractures
–Susceptibility to infection: Cortisol can impair the immune system
–Heart palpitations: A racing heart
–Restlessness: Anxiety
–Constipation: Feeling bloated
–Headaches: 2601:8C:4E80:7578:6138:2331:E1B3:6E99 (talk) 12:39, 13 November 2024 (UTC)[reply]
I'm still not sure what you want changed in the article/what specifically violates WP:NPOV. I requested bullet point sentences and quoted examples of WP:NPOV violations, but instead you've essentially source dumped the USFDA prescribing info - which is already covered extensively in Adderall#Adverse effects (NB: much of that section is transcluded from Amphetamine#Adverse effects and happens to be featured article compliant) - and supplied a google search URL for "side effects of high cortisol", which isn't a MEDRS citation, let alone a citation that discusses side effects of pharmaceutical amphetamine. Professional Crastination (talk) 08:48, 2 December 2024 (UTC)[reply]

MAS title usage

@Gobucks821 I've reverted the changes you made Re: substituting Adderall for "MAS products" throughout the article.

Adderall is the title of this article and the usage of Adderall to refer to the specific amphetamine salt composition in both Adderall and Mydayis dosage formulations is underpinned by previous consensus on this article's talk page. Moreover, the note in the title sentence of this article clarifies the usage of Adderall throughout the article.

For those reasons, in future you need to gain consensus on this article's talk page before making a change like that. Professional Crastination (talk) 05:02, 7 August 2024 (UTC)[reply]

Contra TAAR1 agonism as the mediator of amphetamine actions

Requesting input on this topic here at WikiProject Pharmacology. Thanks. – AlyInWikiWonderland (talk, contribs) 16:00, 13 December 2024 (UTC)[reply]

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