Talk:Adderall

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PHARMA EDITORS TO THIS PAGE

This page paints adderall way too much more positively than is accurate. I believe pharma people may be editing this page! Please check! — Preceding unsigned comment added by 209.2.213.191 (talk) 06:57, 15 November 2016 (UTC)

You need to be a little more specific about what you believe the problem is here. Seppi333 (Insert 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: 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. I am a rock (and an island) (talk) 14:46, 18 November 2016 (UTC)

@I am a rock (and an island): I've attempted to address your concerns accordingly:

• The case report that you cited on 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: USFDA-commissioned studies from 2011 indicate that in children, young adults, and adults there is no association between serious adverse cardiovascular events (sudden death, heart attack, and stroke) and the medical use of amphetamine or other ADHD stimulants.). 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: "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 (Reviews of clinical stimulant research have established the safety and effectiveness of long-term amphetamine use for ADHD.), 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 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 ("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:

  Long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal dopamine system development or nerve damage, but, in humans with ADHD, pharmaceutical amphetamines appear to improve brain development and nerve growth. 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.

• The 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 (Performance enhancement at the cost of potential brain plasticity: neural ramifications of nootropic drugs in the healthy developing brain.) is a medical review, so it can be used to cite statements in this article; 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 (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. Seppi333 (Insert 2¢) 22:35, 18 November 2016 (UTC)

@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 first change you made balances things out with regard to the first sentence I initially mentioned, IMO. The 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 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 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.— Preceding unsigned comment added by ‎I am a rock (and an island) (talk • contribs) BallenaBlanca (Talk) 23:57, 19 November 2016 (UTC)

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. I am a rock (and an island) (talk) 03:55, 20 November 2016 (UTC)

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. Seppi333 (Insert 2¢) 22:18, 20 November 2016 (UTC)

Sorry about the delayed reply. I haven't forgotten about this. I'll follow up once I get home later tonight. Seppi333 (Insert 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 other review which cites that sentence does cover the long-term efficacy of continuous stimulant therapy for core ADHD symptoms. Per its conclusion: 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. Seppi333 (Insert 2¢) 08:02, 23 November 2016 (UTC)

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 you have uploaded, there is the following quote: 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 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.

Thanks for hearing me out on this. I am a rock (and an island) (talk) 21:12, 23 November 2016 (UTC)

@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 by tomorrow night at the latest 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. Seppi333 (Insert 2¢) 01:16, 1 December 2016 (UTC); Updated 04:44, 2 December 2016 (UTC)

@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. Seppi333 (Insert 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 (1,2,3,4) brand names are mentioned and called brand names in the introduction. I am a rock (and an island) (talk) 16:59, 4 December 2016 (UTC)

@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 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 "based upon the longest follow-up studies conducted to date, 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 (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).
  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.
• 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.
  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.

  @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. Seppi333 (Insert 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. Seppi333 (Insert 2¢) 17:36, 5 December 2016 (UTC)

@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. I am a rock (and an island) (talk) 19:58, 7 December 2016 (UTC)

Section references

Grouped references

References

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.

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).

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? 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? 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?

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.

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. 86.153.54.114 (talk) 23:54, 27 December 2016 (UTC)

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? Seppi333 (Insert 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?

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 86.153.54.114 (talk) 16:05, 29 December 2016 (UTC)

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. Garzfoth (talk) 02:39, 30 December 2016 (UTC)

@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 ≫ 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.
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 verifiability.

Re: your claim about NPOV, these two sources - [1] and [2] - 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.

I don't see anything that reads like a "disclaimer" in the side effects section. Can you be more specific? Seppi333 (Insert 2¢) 18:48, 30 December 2016 (UTC)

On a completely off-topic note, it amuses me that the author of this article used the image that I uploaded to commons. Seppi333 (Insert 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!). 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). Garzfoth (talk) 21:12, 30 December 2016 (UTC)

Yes, the taste sometimes makes me cringe if it dissolves in my mouth. Seppi333 (Insert 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. Garzfoth (talk) 21:06, 30 December 2016 (UTC)

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.
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. Seppi333 (Insert 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 ([3]), 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 (PMID 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). Garzfoth (talk) 20:34, 2 January 2017 (UTC)

I don't disagree with what you said. What you've stated and quoted (e.g., clinical practice involves as many as 20% of patients taking doses beyond monograph limits) is entirely consistent with what I've claimed (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. Seppi333 (Insert 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. Garzfoth (talk) 00:15, 3 January 2017 (UTC)

Footnotes

I like the way the footnotes are organized in this article, keeping the clutter out of the article. —PermStrump(talk) 19:03, 30 December 2016 (UTC)

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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. --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. Thunderstorm008 (talk · contributions) 17:03, 5 September 2018 (UTC)

See Special:Permalink/854757323#cite_ref-Adderall_4-0 / Special:Permalink/854757323#cite_note-Adderall-4. The most commonly used term to refer to mixture of amphetamine salts used in Adderall and Mydayis is "mixed amphetamine salts", but that's not an "official" non-proprietary name (e.g., a USAN or INN). Seppi333 (Insert 2¢) 03:45, 6 September 2018 (UTC)

Lab Rat

I was diagnosed with ADD back when I failed the 8th grade ( DOB: 10-11-1986 ) and have been takeing four 30mg pills a day since until all of a sudden the insurance company's decided they know what's best and would only cover up to only two 30mg a day...... who are they to call the shots like that? Last time I checked, they dont have the credentials to make this clame and I would like to know who can officially say they are wrong because I know. I'm a statistic with paperwork to back me up and I want answers damnit. Kevkarnes1 (talk) 11:45, 2 March 2019 (UTC)