Talk:Lisdexamfetamine

"indicated"

I changed wording of "indicated" to "can be prescribed"..."for treatment". Although use of the word indicated is generally understood by the medical profession to mean that it has been approved for use by the FDA, I'm concerned that use in this article implies to readers that "indicated" could mean the non-medical jargon use of the word which is defined as "suggest as a desirable or necessary course of action." with synonyms to the non-medical use of "indicated", being:: "advisable, recommended, suggested, desirable, preferable, best, sensible, wise, prudent, in someone's best interests"-----which is not always the case in drug use, although again, in medical jargon, "indicated" means something else.24.0.133.234 (talk) 14:13, 13 June 2014 (UTC)

Thanks; I'll change this in all the high traffic amphetamine articles that use this language when I get a chance. Seppi333 (Insert 2¢ | Maintained) 17:23, 13 June 2014 (UTC)

Promotional and uncritical

This entry looks very promotional and uncritical, which is a concern because many critics complain that Shire is been promoting its drugs heavily and inappropriately to the public. Here's a recent article in the New York Times:
http://www.nytimes.com/2015/02/25/business/shire-maker-of-binge-eating-drug-vyvanse-first-marketed-the-disease.html?
Shire, Maker of Binge-Eating Drug Vyvanse, First Marketed the Disease
By KATIE THOMAS
FEB. 24, 2015
(Vyvanse (Shire) is an amphetamine prodrug, $1.5 billion/year sales, recently new approval for binge eating. FDA granted priority approval, without advisory committee hearings or recommendations, because there was no other drug to treat binge eating. Shire hired retired tennis player Monica Seles to make the talk show circuit to promote awareness of binge eating. Shire similarly promoted Adderall and Vyvanse for ADHD. Lawrence H. Diller, behavioral pediatrician, Walnut Creek, CA, and critic of ADHD treatment, quoted. Shire web site on binge eating disorder offers printable symptom checklist and opening lines to start conversation with doctor, tells patients “don’t give up” if a doctor initially resists. Critics say "appeared to coach patients about how to receive a diagnosis for a relatively uncommon condition, or shop for a new doctor if they were not successful.")

This entry also seems to be quoting selectively from the Cochrane reviews. Here's one that I got with a search for lisdexafetamine:
http://www.aafp.org/afp/2012/0901/p413.html
Amphetamines for Attention-Deficit/Hyperactivity Disorder in Adults
Am Fam Physician. 2012 Sep 1;86(5):413-415.
Authors' Conclusions: Amphetamines improved short-term ADHD symptom severity. Mixed amphetamine salts also increased retention in treatment. Amphetamines were associated with higher attrition due to adverse events. The short study length and the restrictive inclusion criteria limit the external validity of these findings. Furthermore, the possibility that the results of the included studies were biased was high, which could have led to an overestimation of amphetamine efficacy. --Nbauman (talk) 17:17, 25 February 2015 (UTC)

If you'd like to add something on Shire and their promotion/marketing of the Vyvanse brand of lisdexamfetamine, please feel free to do so; this material would be appropriate for the Lisdexamfetamine#History, society, and culture section if you wish to add it.
As for the Cochrane reviews, that content is transcluded from amphetamine, which is a featured article; hence, that statement is unlikely to change due to the editorial consensus on its quality. Personally, I don't think the omission of qualitative statistical information is misleading, especially when there is corroborating evidence of the underlying conclusion from other sources. Seppi333 (Insert 2¢ | Maintained) 23:06, 3 March 2015 (UTC)

why precursor?

Why would anyone take a dextroamphetamine precursor when you can buy actual dextro? Verdana♥Bøld 23:10, 22 November 2015 (UTC) — Preceding unsigned comment added by Verdana Bold (talk • contribs)

What text in the article are you referring to? Seppi333 (Insert 2¢) 23:12, 22 November 2015 (UTC)

He doesn't refer to a specific point in the text. He points out that on the entire page, there is not a single reason mentioned what the benefits are for using a prodrug. It definitely is one of the most important questions that should be answered on the page. Otherwise the page isn't any different from the regular (dex)amphetamine page.

The main of advantage of prodrugs is that they are released more slowly and evenly in the system. This could lower the plasma peak in the user and potential side-effects. That the lisdexamfetamine gets released more slowly in the usersystem can be seen from the "Onset of Action" in the general information bar on the wikipages. The onset of action is for lisdexamfetamine 2 hours. For regular (dex)amphetamine the onset of action is 30 - 60 minutes.

The lisdexamfetamine has about the same tolerability and effectiveness as extended release dexamphetamine. Lisdexamfetamine also has potentially lower abuse potential.

This article mentions a couple differences between lisdexamfetamine and dexamphetamine. Rowley, H. (2012). Lisdexamfetamine and immediate release d-amfetamine–Differences in pharmacokinetic/pharmacodynamic relationships revealed by striatal microdialysis in freely-moving rats with simultaneous determination of plasma drug concentrations and locomotor activity. Neuropharmacology, 63(6), 1064-1074."

References

Bonnom (talk) 15:55, 29 April 2016 (UTC)

Addiction

Why is the single largest section on this page a generic amphetamine addiction cut/paste? At one point it even goes into addiction recovery and opiate addiction. Amphetamine addiction is almost entirely the result of abuse. Lisdexamfetamine MOA makes it very hard (impossible?) to abuse... information that isn't even mentioned. — Preceding unsigned comment added by Billyoffland (talk • contribs) 15:55, 12 March 2016 (UTC)

LDX is an inactive prodrug for what you call "generic amphetamine", hence it shares its addiction mechanisms. If you have read in a medical review that LDX is "hard/impossible to abuse" then cite it. Seppi333 (Insert 2¢) 16:16, 12 March 2016 (UTC)

The point is being missed. Neither Water or Properties of water make any mention of drowning potential or methods of resuscitation. This article is on Lisdexamfetamine. Not Lisdexamfetamine addiction / addiction recovery. Alcohol, Nicotine and Opiate make no / limited mention of addiction / recovery. Notoriously addictive Oxycodone and Benzodiazepine (eg Alprazolam) also make appropriately limited mention of related but not necessary relevant topics. Here is an NIH report on the reduced abuse potential of Lisdexamfetamine http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873712/ that can be included in this article as it's directly related to Lisdexamfetamine specifically.

More commonly, "Generic" means generally related to. I said the cut/paste was of generic (as in relating to general) "amphetamine addiction". "LDX" (as you call it) is indeed a prodrug. "hence it shares its addiction mechanisms" is not accurate. The very information in your cut/paste on addiction talks about dependence verses addiction verses addictive behaviors.Billyoffland (talk) 15:41, 14 March 2016 (UTC)

Anything relevant to LDX's addiction liability belongs in this article per MOS:MED. The same is true for every single article that you just linked. The only difference is that the amphetamine article is much more thorough. That article content is not a "cut and paste", it's a transclusion just as the article says. My statement that it shares its addiction mechanisms is indeed accurate. The prodrug isn't addictive since it isn't even biologically active; every effect that LDX has on the brain is mediated through dextroamphetamine. Hence, it shares its addiction mechanisms.

I don't mind mentioning that it's less abusable relative to dextroamphetamine, but it's not even remotely true that the drug has no recreational potential or isn't addictive. Seppi333 (Insert 2¢) 21:55, 14 March 2016 (UTC)

I've added it under the addiction heading. Seppi333 (Insert 2¢) 22:26, 14 March 2016 (UTC)

The substance onset determines partly the addictiveness of a substance. That's why injecting drugs is more addictive than any other method of taking drugs. The lisdexamfetamine has a slower onset than regular amphetamine. I know rehab clinics that give patients(addicts) extended release variants because they think it is less addictive and it is less likely to be for abused. I don't know if this has be proven. Lisdexamfetamine is likely to be less addictive when used intravenous. I only doubt if this is a real issue. There isn't any evidence that amphetamine is addictive when used like recommended by a doctor. Bonnom (talk) 16:16, 29 April 2016 (UTC)

Lisdexamfetamine and Lisdexamphetamine

I was recently prescribed this I came here for some more info. The page is named 'Lisdexamfetamine' but it is spelled as 'lisdexamphetamine' several times throughout. I looked up this difference and it seems to be the same thing as color/colour and armor/armour where it is just the British spelling and the U.S. spelling. I know that even a two letters difference can mean wildly different chemicals. I'm posting this here because I want to give a notice before I change what I can to make it more parsimonious. I'll be changing every 'lisdexamfetamine' to 'lisdexamphetamin' to help clear the confusion of using two different words for the same thing — Preceding unsigned comment added by Sigil47 (talk • contribs) 02:50, 16 May 2016 (UTC)

The correct spelling of this drug is with an f, not a ph. That's a fairly common typo. Seppi333 (Insert 2¢) 05:34, 16 May 2016 (UTC)

Hi, can you justify why it is named that?

There doesn't seem to be any justification for what appears to be a popularized misspelling of the word "lisdexamphetamine", a non-proprietary chemical name.

Non-proprietary meaning that both it's nomenclature has etymological roots, and is particularly important to represent correctly because the name further represents it's chemical structure.

Being spelled differently implies structural differences which may exist, but should be clarified and pointed out 71.251.231.214 (talk) 22:03, 15 September 2023 (UTC)

Correct me if I'm wrong but it looks like a series of contractions rather then American vs British.

lisdexamphetamine is defined as (2S)-2,6-Diamino-N-[(1S)-1-methyl-2-phenylethyl]hexanamide

Lisdexamfetamine is noted to be a contraction of L-lysine-dextroamphetamine, which is a contraction of

(2S)-2,6- diamino-N-[(1S)-1-methyl-2-phenylethyl]hexanamide dimethanesulfonate 71.251.231.214 (talk) 23:03, 15 September 2023 (UTC)

Merge?

Is there any reason to have this article and dextroamphetamine separate from amphetamine? Jytdog (talk) 22:36, 10 July 2017 (UTC)

Amphetamine and dextroamphetamine are clearly very similar, but they're still distinct drugs. Lisdexamfetamine is an entirely different compound altogether though. There have been several merge proposals over the years about combining these pages but it has never done for various reasons. Seppi333 (Insert 2¢) 22:50, 10 July 2017 (UTC)

Yes they are but their actions are almost entirely the same.... we could have one article and just describe the different chemicals in the chemistry section, no? Jytdog (talk) 22:55, 10 July 2017 (UTC)

The main differences between the articles are their medical indications (amphetamine has more than d-amph, LDX has one that neither amphetamine nor d-amph has) and their historical/cultural aspects. That'd probably be a bit difficult to cleanly partition and cover in 1 article. I agree that it's sort of redundant to have 3 pages on this, but I don't really see the harm in keeping them apart. It's certainly simpler than trying to merge them into amphetamine and maintaining FA-quality prose in the process though. FWIW, I don't actually remember any of the past arguments for/against keeping these pages separate. Seppi333 (Insert 2¢) 23:02, 10 July 2017 (UTC)

Man these articles are incredibly intricately networked! Jytdog (talk) 23:30, 10 July 2017 (UTC)

Lol. A while back, I got really tired of updating Adderall, lisdexamfetamine, and dextroamphetamine every time I made a change to amphetamine that was relevant to those 3, so the simplest way to solve that problem was just to transclude to all of them. Seppi333 (Insert 2¢) 23:42, 10 July 2017 (UTC)

Duration of action

The article claims a duration of action of 10-12 hours which is twice as long as normal dexedrine. Considering that lisdexamphetamine is metabolised into its active ingredient dexamphetamine within one to two hours this doesn't make sense to me. I suggest someone with access to sources 2, 4 and 5 checks whether they support this claim. 12:58, 21 April 2018 (UTC) — Preceding unsigned comment added by 92.218.227.67 (talk)

The duration is correct. The longer duration reflects the extended release dosage forms of all current lisdexamfetamine pharmaceuticals, which are combined with inactive polymers that slow their absorption. The duration of action of a hypothetical "immediate release" lisdexamfetamine dosage form hasn't been published in academic literature, but I assume it would be roughly the same as IR dextroamphetamine formulations. Seppi333 (Insert 2¢) 19:05, 21 April 2018 (UTC)

Incorrect, Vyvanse/Elvanse are instant release hard capsules. It's not known yet, although this paper theorizes that it's due to reduced acute tolerance. 77.102.70.58 (talk) 19:49, 12 June 2022 (UTC)

@Seppi333, is this true? 2403:4800:3494:8D00:4511:6181:766D:2864 (talk) 14:08, 14 October 2022 (UTC)

They are indeed instant-release capsules, which is further supported by the fact that breaking open the capsules, mixing the contents in water, and drinking said solution is an officially approved alternative method for taking the drug. The time-delay attributes are present due to the fact that this is a prodrug that can only be converted into an active form through rate-limited hydrolysis within the bloodstream. Until the drug reaches the bloodstream, it remains totally inert, and even after reaching the bloodstream, the rate-limiting hydrolysis takes roughly 3 hours to process all of the prodrug into the active form.

I'm not sure where the original poster got the "one to two hours" figure from, as it doesn't align with the pharmacokinetic data in the literature.

I am highly doubtful of the claims in Seppi333's comment from 2018.

The longer duration is correct to an extent, but it stems from the LDX->DEX conversion being rate-limited by the requirement to undergo rate-limiting hydrolysis within the bloodstream to produce the active drug combined with the high initial loading dose of the prodrug. Obviously a similarly high initial loading dose of IR dex would not be tolerable.

I do not recall ever reading anything in the literature regarding the use of inactive polymers to slow absorption of the drug, and I am not sure that these would play a significant role if they even are used. I'd need to do some additional research to determine what they're referring to. I am doubtful that this is accurate.

The claim that a IR LDX dose would have a roughly identical duration of action to IR dex is complicated — on the surface, this is false, but the level of technical nuance here makes it hard to say that they're not still partially accurate in certain senses... It depends on the relative doses used. Overall, I'd say it is highly misleading at absolute best.

I hope this helps clear things up. Garzfoth (talk) 19:51, 14 October 2022 (UTC)

Re: The longer duration reflects the extended release dosage forms of all current lisdexamfetamine pharmaceuticals, which are combined with inactive polymers that slow their absorption. The duration of action of a hypothetical "immediate release" lisdexamfetamine dosage form hasn't been published in academic literature, but I assume it would be roughly the same as IR dextroamphetamine formulations. I find it a bit bizarre that I actually wrote this given that I know LDX is just formulated as an inactive prodrug and its conversion to dextroamphetamine is, as Garzfoth restated, mediated by a rate-limiting enzyme in blood. I suppose I could've conflated LDX and ER amphetamine salt formulations if I were drunk and/or half-asleep or drunk, but I honestly don't remember what I was thinking when I wrote that. In any event, what I originally wrote is, indeed, completely wrong.

As far as explaining differences in duration of action, that's a clinical measure, whereas half-life and other pharmacokinetic measures are commonly used to explain differences in it between drug formulations. It is possible that a pharmacodynamic mechanism can mediate observed differences in duration of action between formulations (e.g., daily tachyphylaxis followed by overnight sensitization to some unspecified psychoactive drug effect, as stated/implied in [1]), but that sounds a bit like nonsense in this particular case since there's no evidence of any cyclical drug effects that rapidly undergo tolerance and then sensitization; and, it could also be mediated by an entirely different system (e.g., pharmacomicrobiomic, pharmacogenomics, etc.) that impinges upon how drugs affect the body and the body affects a drug.

Regardless of what other mechanisms may be involved, saturation of the rate-limiting enzyme that converts LDX to D-amph at prescribed doses of LDX unequivocally contributes to a longer duration of action of LDX. Seppi333 (Insert 2¢) 20:19, 21 November 2022 (UTC)

Ambiguous statement

@Doc James: Can you restore this statement with clarification? I don't know what this means and I imagine neither do our readers. In what context and by whom is this less preferred? E.g., by British adults for the treatment of ADHD? By American children for the same purpose?

"It is usually less preferred than methylphenidate."

Seppi333 (Insert 2¢) 06:58, 17 April 2019 (UTC)

Sure added that this is in the UK Doc James (talk · contribs · email) 14:40, 17 April 2019 (UTC)

References

Which ref supports this

"Chemically, lisdexamfetamine belongs to the class of substituted amphetamines."

Not saying it is incorrect. But if not source makes the claim it makes one wonder how notable it is? Probably best to go in the body of the text regardless.

Doc James (talk · contribs · email) 14:40, 17 April 2019 (UTC)

That’s literally the only chemistry statement in a paragraph you’ve marked as “mechanism and chemistry”, so I’m not sure why you want to remove it. I don’t have a source on-hand, but I don’t think a source is necessary for a statement like this given that the amphetamine backbone in lisdexamfetamine’s structure diagram is clearly visible. It’s almost a “sky is blue” statement. Seppi333 (Insert 2¢) 03:35, 18 April 2019 (UTC)

No it is not a "sky is blue" statement. Please provide a source. It is not something that is obvious by just looking at it... Doc James (talk · contribs · email) 17:49, 18 April 2019 (UTC)

The first sentence in https://www.ncbi.nlm.nih.gov/pubmed/17407369 implies that it is a substituted amphetamine; however, since I am sure you are going to take that statement at face value instead of what it implies, I will opt to use the more technical language of the source and state that "Chemically, lisdexamfetamine is composed of the amino acid l-lysine covalently bonded to dextroamphetamine". Seppi333 (Insert 2¢) 07:53, 19 April 2019 (UTC)

Okay have simplified a bit. Doc James (talk · contribs · email) 17:39, 19 April 2019 (UTC)

Pregnancy and breastfeeding

Does anyone recommend its use? All the sources including the manufacturer recommend against such use. Unless someone reputable states otherwise we can just state it as fact. Doc James (talk · contribs · email) 14:45, 17 April 2019 (UTC)

We can’t do that because of WP:WikiVoice. If we don’t attribute that statement, the recommendation is implicitly coming from us. I’m sure you remember the heated discussion I had with SandyGeorgia and RexxS about assertions like this at WT:MED. Attributing it is really not a big deal. Seppi333 (Insert 2¢) 03:16, 18 April 2019 (UTC)

But everyone says the exact same thing... We can just state the facts. Do you have a single source that says use is recommended during breastfeeding?

I could easily write a page of all the sources that make this recommendations but that would be silly. Doc James (talk · contribs · email) 17:53, 18 April 2019 (UTC)

Attribution to the manufacturer I guess would be fine. Doc James (talk · contribs · email) 17:44, 19 April 2019 (UTC)

Serotonin syndrome

May occur not just in overdose but when this is used in combination with other medications per the source.[2] Doc James (talk · contribs · email) 14:45, 17 April 2019 (UTC)

Then that's not a side effect; it's a drug interaction. Seppi333 (Insert 2¢) 20:48, 17 April 2019 (UTC)

Okay clarified. Doc James (talk · contribs · email) 17:53, 18 April 2019 (UTC)

Mania versus psychosis

These are two different conditions within psychiatry and the reference deals with them separately. Ref says "Manic symptoms may occur with usual dosages in children and adolescents without prior history of mania."[3] Doc James (talk · contribs · email) 14:48, 17 April 2019 (UTC)

Fair enough. Seppi333 (Insert 2¢) 20:48, 17 April 2019 (UTC)

CNS stimulant

Lisdexamfetamine is classified as a CNS stimulant. This is despite the fact that it is converted into dextroamphetamine first. Just because something requires metabolism in the body does not mean it is not in that class of medications. Stating that it "works after being converted by the body" is how one says in common English that it is a prodrug. Technical terminology can generally go in the body. Doc James (talk · contribs · email) 14:53, 17 April 2019 (UTC)

Sigh. I suppose that'll do for now. Seppi333 (Insert 2¢) 20:49, 17 April 2019 (UTC)

Lead

Ideally, this statement in the lead - Serious side effects may include sudden cardiac death, mania, and psychosis.[3] It has a high risk of abuse.[3][dubious – discuss] - should be rephrased to mirror these statements (N.B. the prevalence of amphetamine psychosis at therapeutic doses is about 1 in 1000):

Larger doses of amphetamine may impair cognitive function and induce rapid muscle breakdown. Drug addiction is a serious risk with large recreational doses but is unlikely to arise from typical long-term medical use at therapeutic doses. Very high doses can result in psychosis (e.g., delusions and paranoia) which rarely occurs at therapeutic doses even during long-term use. Recreational doses are generally much larger than prescribed therapeutic doses and carry a far greater risk of serious side effects.
— Amphetamine lead

• The problem with stating that sudden cardiac death is a serious side effect is that it doesn't occur in individuals who do not have cardiovascular disease (re: 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 ], heart attack, and stroke) and the medical use of amphetamine or other ADHD stimulants.); cardiovascular disease is a contraindication for that reason.

• I dislike the phrase "drug abuse". Drug abuse is not a well-defined term or even a medical term; I equate that phrase with "misuse as a recreational drug", which I don't think is particularly notable given that any euphoriant can and will be "abused"/misused as such intentionally by some people. Covering lisdexamfetamine's addiction and/or dependence (i.e., amphetamine use disorder) liability is the ideal way to broach that subject IMO.

• Re pregnancy: instead of stating a recommendation, we could state why the recommendation was made; i.e., summarize "Evidence from human studies indicates that therapeutic amphetamine use does not cause developmental abnormalities in the fetus or newborns (i.e., it is not a human teratogen), but amphetamine abuse does pose risks to the fetus." Alternatively, we could attribute the recommendation; I don't care either way. All other recommendations/normative statements in this article are attributed already.

Seppi333 (Insert 2¢) 05:26, 18 April 2019 (UTC)

The reference says "High potential for abuse"[4]. Abuse potential is listed as a boxed warning even. Doc James (talk · contribs · email) 17:51, 18 April 2019 (UTC)

Have this ref Stahl SM (March 2017). "Lisdexamfetamine". Prescriber's Guide: Stahl's Essential Psychopharmacology (6th ed.). Cambridge, United Kingdom: Cambridge University Press. pp. 379–384. ISBN 9781108228749.

On page 379 it says "Schedule II drug". It does not say "moderate risk of psychological dependence"?

Doc James (talk · contribs · email) 18:19, 18 April 2019 (UTC)

I never said that it didn't have a high potential for abuse; I did not add the dubious tag to the article. What I said was the term "drug abuse" is an ill-defined non-medical term and therefore we should opt to use different language. Seppi333 (Insert 2¢) 07:58, 19 April 2019 (UTC)

Certainly. "Abuse" is the common term and is the one used by the sources. Doc James (talk · contribs · email) 17:38, 19 April 2019 (UTC)

References

Physical dependence

Appears we have decent sources saying there is no physical dependence or that their is physical dependence at high doses.

For example see [5] Doc James (talk · contribs · email) 17:40, 19 April 2019 (UTC)

The symptoms they list under physical dependence reflect psychological dependence. Seppi333 (Insert 2¢) 20:52, 19 April 2019 (UTC)

Re your other ref: https://books.google.ca/books?id=VuhGDQAAQBAJ&pg=PA374#v=onepage&q=physical%20dependence&f=false. This doesn't list any symptoms; however, see on page xiii: "Dependence as used in this book refers to physical dependence: the body' adaption to a drug upon cessation or reduction of the drug, the manifestation of withdrawal symptoms." Physical dependence is conflated with dependence in this book. Seppi333 (Insert 2¢) 21:00, 19 April 2019 (UTC)

The ref says "Chronic amphetamine use produces physical dependence".[6] Prolonged sleep is physical withdrawal not psychological. Doc James (talk · contribs · email) 01:01, 20 April 2019 (UTC)

No, it’s not; physical dependence entails visible somatic withdrawal symptoms such as seizures, tremors, or sweating. Even if it were though, why would we refer to insomnia and wakefulness as psychological side effects of this drug and hypersomnia as a physical withdrawal symptom? Seppi333 (Insert 2¢) 01:34, 20 April 2019 (UTC)

Ah the physical withdrawal symptoms are typically the opposite of the effects of the drug. So yes for depressants you have described the physical withdrawal symptoms. However for stimulants the state of physical withdrawal is a state of depressed functioning. Doc James (talk · contribs · email) 02:50, 20 April 2019 (UTC)

RfC about whether or not lisdexamfetamine has physical dependence

The following discussion is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

---

High quality sources disagree. Thus for "dependence liability: physical" we should put either "controversial" or "disputed".

We have multiple high quality sources that support physical dependence. We have the following text under the heading for "lisdexamfetamine" in this medical textbook.

Physical dependence. Chronic amphetamine use produces physical dependence. If amphetamines are abruptly withdrawn from a dependent person, an abstinence syndrome will ensue. Symptoms include exhaution, depression, prolonged sleep... Rosenthal, Laura; Burchum, Jacqueline (2017). Lehne's Pharmacotherapeutics for Advanced Practice Providers - E-Book. Elsevier Health Sciences. ISBN 9780323447799.

We also have the current source which says

cessation of cocaine use and the use of other psychostimulants in dependent individuals does not produce a physical withdrawal syndrome but may produce dysphoria, anhedonia, and an intense desire to reinitiate drug use.

Doc James (talk · contribs · email) 04:49, 22 April 2019 (UTC)

Option 1: Use "disputed"

• Support as proposer. The withdrawal syndrome seen with a substance is generally the opposite of the effects it causes. Thus stimulants result in a withdrawal syndrome that is associated with exhaution and prolonged sleep. Well depressants like alcohol result in an agitated withdrawal state. Doc James (talk · contribs · email) 04:49, 22 April 2019 (UTC)
• support per Doc James rationale--Ozzie10aaaa (talk) 11:10, 22 April 2019 (UTC)
• Support. Newer sources are increasingly indicating that it is outdated to state stimulants cause no physical dependence. Lots of evidence exists that changes in receptor numbers/sensitivity and dopamine transporter levels occurs with long-term use of psychostimulants which manifests in some susceptible people as a withdrawal syndrome. Granted the severity of physical dependence is likely much less than that of say alcohol, benzodiazepines etc., but it still exists.--Literaturegeek | T@1k? 19:02, 22 April 2019 (UTC)
  • @Literaturegeek: You are conflating physical dependence with dependence. Seppi333 (Insert 2¢) 10:06, 23 April 2019 (UTC)
    • @Seppi333: I don’t think so, the fact tolerance and partial tolerance (a need to take increased doses to achieve the same effect) as a result of chronic use of stimulants followed by a withdrawal syndrome occurs is the very definition of physical dependence.--Literaturegeek | T@1k? 13:30, 23 April 2019 (UTC)
      • @Literaturegeek: Not the one we use. Seppi333 (Insert 2¢) 03:20, 24 April 2019 (UTC)

Option 2: Use "none"

• Support as the sources provided are crap as I've explained above. Moreover, I'm baffled as to why Doc James is arguing that modulation of circadian cycles is a physical drug effect. Seppi333 (Insert 2¢) 08:23, 22 April 2019 (UTC) We just list "dependence" now. Seppi333 (Insert 2¢) 09:24, 22 April 2019 (UTC)
• Oppose per my rational expressed in my other votes here.--Literaturegeek | T@1k? 19:04, 22 April 2019 (UTC)

Option 3: Leave out physical dependence from the infobox

• Support Happy with this aswell. Agree it is controversial and likely best to reflect this in the body of the text. Doc James (talk · contribs · email) 16:53, 22 April 2019 (UTC)
• Oppose lots of things are controversial, doesn’t mean we exclude them.--Literaturegeek | T@1k? 18:58, 22 April 2019 (UTC)
• This is what we are going to end up doing. Seppi333 (Insert 2¢) 10:06, 23 April 2019 (UTC)

Option 4: Leave as "high"

• Support - Maybe I'm confusing this, but it seems like this is a debate over what is "physical" versus "psychological" dependence. I'm obviously no expert, but my initial sentiment is that the infobox doesn't really distinguish different kind of dependencies and we ought to list any kind of dependence as just dependence. NickCT (talk) 20:46, 25 April 2019 (UTC)
  • Woops! I now see I joined this discussion a little late..... Can someone close this RfC if we've reach consensus on this topic? NickCT (talk) 20:52, 25 April 2019 (UTC)

Discussion

Lots of more examples of books that mention physical dependence from stimulants

• "both indicating a form of physical dependence, occurs in heavy users"[7]
• With respect to amphetamines "physical dependence is moderate"[8]
• "the existance of tolerance and physical dependence is more controversial than with the preceding clases, though there is some evidence for a withdrawal syndrome"[9]

Doc James (talk · contribs · email) 05:05, 22 April 2019 (UTC)

• [6] is about cocaine
• re: "amphetamines" - this term reflects an enormous class of structural and functional analogs (i.e., a chemical class much larger than substituted amphetamines) with markedly varied pharmacology.
• "the existance of tolerance and physical dependence is more controversial than with the preceding classes, though there is some evidence for a withdrawal syndrome characterised by general weakness and low mood" - why did you leave out the part where they specify symptoms of psychological dependence? Is it because it contradicts your argument? I'd wager that's the reason for your omission.
• Re: the reference at the top of this RFC that says "cessation of cocaine use and the use of other psychostimulants in dependent individuals does not produce a physical withdrawal syndrome but may produce dysphoria, anhedonia, and an intense desire to reinitiate drug use. - read physical dependence and psychological dependence.

Even if any of these references actually specified physical withdrawal symptoms like seizures or tremors for cocaine, "amphetamines", or stimulants, adding it to this article to cite an assertion that this drug induces physical dependence would constitute WP:OR because the sources don't say this. Moreover, since diagnostic manuals used to conflate the term "physical dependence" with "dependence", any source which doesn't specifically list a physical withdrawal symptom is highly suspect. But, at the very least, if you want to assert that lisdexamfetamine causes physical dependence, then find a source which states that lisdexamfetamine produces physical withdrawal symptoms.
Nevermind; I have a feeling this argument is going to be drawn out and a massive waste of editing time; since discussing this will be moot if we just cut "physical" and "psychological" from the drugbox, I'm opting for this solution. Seppi333 (Insert 2¢) 08:45, 22 April 2019 (UTC)

• Yes that ref was about cocaine which is why I said that these were refs about stimulants
• No adding "characterised by general weakness" does not contradict my argument and I am happy to see it included.
• Per physical dependence first sentence says "is a physical condition caused by chronic use of a tolerance forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms." Yes generalized weakness and excessive sleeping are unpleasant physical symptoms.
• Seizures and tremors are the physical withdrawal symptoms of depressants not stimulants. No one has claimed that stimulant withdrawal results in those symptoms. But those are not the only possible physical withdrawal symptoms.
• I have provided a source that lists the physical withdrawal symptoms of lisdexamfetamine in the opening of this RfC.Doc James (talk · contribs · email) 16:42, 22 April 2019 (UTC)

I agree that Seppi's recent change makes this moot. User:Doc James, maybe this RFC should be withdrawn? WhatamIdoing (talk) 17:57, 22 April 2019 (UTC)

Yes if we have consensus to do this, for this topic. Doc James (talk · contribs · email) 18:00, 22 April 2019 (UTC)

• comment psychological symptoms such as psychosis, anxiety, depression, sleep disturbance etc., can and frequently are a consequence of physical dependence (physiological adaptations). Not sure if this is understood in the above conversation.--Literaturegeek | T@1k? 19:25, 22 April 2019 (UTC)

• I am not suggesting that we leave out discussion entirely, simple that I am okay with discussion going in the body of the text rather than the infobox. Doc James (talk · contribs · email) 19:08, 23 April 2019 (UTC)

The discussion above is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

Consensus to add a second "side effects" section

Not seeing it here. Not seeing it at WP:MEDMOS. I oppose this. Doc James (talk · contribs · email) 11:14, 23 May 2019 (UTC)

First sentence

This IMO does not belong in the first sentence "codrug composed of the amino acid L-lysine, attached to dextroamphetamin"

Doc James (talk · contribs · email) 16:09, 29 November 2019 (UTC)

Major rewrite cleanup needed

This article has a surprisingly bad noise/data ratio. Too much is transcluded or just pasted from [amphetamine] or similar articles, not directly specific to Lisdexamfetamine. The result is an essentially useless article that looks very detailed and authoritative, but requires too much effort to find out what is actually relevant to the subject matter. It might be relevant to have links to amphetamine data when there is none available that is specific to Lisdexamfetamine, but not pretend it should simply be pasted here. YamaPlos talk 19:19, 10 July 2020 (UTC)

If anything, the Pharmacology and Adverse effects sections can just link to amphetamines. Those sections just draw away from the main subject at hand. – The Grid (talk) 01:48, 12 July 2020 (UTC)

Changing “dependence liability” from “high” to “moderate”

I have revised the dependence liability of lisdexamfetamine to moderate to align with the growing body of evidence and current expert consensus that lisdexamfetamine has an appreciably lower potential for dependence compared to that of dextroamphetamine (Dexedrine) or mixed amphetamine salts (Adderall). RiMediaN (talk) 01:20, 30 March 2021 (UTC)

Drugs.com not really appropriate, but what's the relevant quote in the former article? ProcrastinatingReader (talk) 01:36, 30 March 2021 (UTC)

References

CDS & Lisdexamfetamine

On this edit, @WikiLinuz: reversed my edit mentioning cognitive disengagement syndrome (CDS) as a treatable condition by lisdexamfetamine on the basis of the secondary source being an "advocacy study" thus not gaining sufficient recognition. This criticism is unfounded. CDS has reached the threshold of recognition as a distinct syndrome as established by the International Consensus Statement on CDS, which I cited as part of my edit, in addition to the primary research it reviews. It is not a promotive idea, but rather a statement of fact, as the scientific consensus makes plain. It is not an "advocacy study". To claim it has not reached the recognition threshold is to contradict the international scientific consensus.

Please note that the current status of diagnostic manuals are quite irreverent as they are not leading the research, but follows it and often a decade or two behind where the research is at the time. And the decisions made by the APA for instance are also political, not just scientifically-based so its hard to know where this will go in the subsequent DSM version. Thus the condition not being recognised in diagnostic manuals does not preclude it from being a distinct syndrome.

Therefore, this edit should not have been redacted on this article. Please discuss/refute/or attest if my understanding of the guidelines here are misled. Димитрий Улянов Иванов (talk) 19:59, 18 February 2024 (UTC)

Responded to it here. --WikiLinuz (talk) 22:08, 18 February 2024 (UTC)

@Димитрий Улянов Иванов: Please gain consensus here before restoring. Until then the article must be in WP:STATUSQUO. --WikiLinuz (talk) 01:10, 20 February 2024 (UTC)

Narcolepsy transclusion

@Seppi333 Hey

I went ahead and wrote the narcolepsy section for medical uses on the main page (thank you for your pointers, BTW =D). That said, I'm specifically posting this on the lisdexamfetamine talk page because I'm curious to hear your thoughts on having the transclusion for narcolepsy on the article of this particular amphetamine formulation?

Obviously, narcolepsy isn't an approved indication for lisdexamfetamine and I've only come across one review that described off-label use for narcolepsy (an aside, that ref incorrectly described vyvanse as "lisamphetamine", which made me laugh). I do realise that lisdexamfetamine/vyvanse does get used off-label for narcolepsy, if only because I have a friend IRL that is prescribed that medication + IR dextroamphetamine salts for NT1. In any event, my first instinct is that the transclusion might not be relevant for this article, particualy because lisdexamfetamine is not mentioned in any of the sources I ended up citing (not including the "lisamphetamine" one that I didn't end up citing anyway, I just feel like typing it again because it sounds funny lol).

Besides getting your input, I'm also tagging you because I'm actually a novice when it comes to wiki source code. So, I wouldn't know how to remove certain sections of a selective transclusion even if I wanted to.

Thanks :3 Professional Crastination (talk) 17:30, 26 May 2024 (UTC)

Also, I'm only adding a reply to this now because I've just noticed that this article doesn't cover vyvanse's binge eating disorder indication. I'm more than happy to do a lit search and write that section sometime in the next week or two (i.e., when my university exam period ends). Unlike selectively excluding sections from transclusions, I'm at least aware how to selectively add sections to this article via "if pagename | Lisdexamfetamine=". I'm bringing this up mainly to see if it has any bearing on your thoughts regarding whether this article should keep the medical uses section on narcolepsy, or not. That said, with a BED section, the exclusion of the narcolepsy section won't result in this article having comparatively less coverage on medical uses.

In any event, no rush on getting back to me, as I understand that you're likely busy with work/off-wiki responsibilities. A lot of my time is preoccupied with exams at the moment, so I'm in no rush to proceed :). Professional Crastination (talk) 16:35, 28 May 2024 (UTC)

I'm sure LDX is used off-label for narcolepsy in the United States and perhaps on-label elsewhere, so I don't have a problem with adding it here. I haven't looked at the source code, but what you wrote and how it renders in both articles both look good. Feel free to add content on BED if you'd like. I haven't been very active lately due to off-wiki obligations. Seppi333 (Insert 2¢) 01:04, 29 May 2024 (UTC)

I went ahead a wrote/cited content for the BED section for this article. However, instead of uploading the source code directly to this article, I added it to the amphetamine article instead and intentionally wrote the source code in a manner that would only render that section's content (i.e., use in BED) on the LDX article. I chose not to also render it on the amph article because all of the sources I cited cover LDX's clinical use and efficacy in BED exclusively, relative to other amphetamine dosage-formulations.

Whilst this was mainly for cosmestic reasons in order to render medical uses in alphabetical order (i.e., ADHD > BED > NT1&2) - as I'm not aware of any way to insert non-transcluded content smack-bang in the middle of a transcluded section - in retrospect, it's probably also a bit odd to have BED content render below narcolepsy (IMO; I can't see anything about order medical uses in MOS:PHARM), given that narcolepsy technically isn't a USFDA-approved indication for LDX, whereas BED is.

With all that said, whilst this might not be that important, I did want to check with you just to be sure that, for the reasons above, it's fine to have the ~17,000 byte source code included in the amph article's source code in the event that its content is only rendered on the LDX article? I figure that I'd ask you specifically because I noticed that I'm actually ranked second on authorship attribution on the main amph article now, whereas your authorship attribution is something like 7x more characters than mine. So, if anyone originally set up these transclusions, I would take my chances on it being you.

Edit: Despite what I said above about the citations describing the clinical use and efficacy of LDX and not other amph dosage formulations, I'm personally not opposed to having the BED content render on the main amph article, in the event that you believe the content, as written, will make a meaningful contribution to that article; I'll let you be the judge of that. If it's a yes, I'll happily change the source code. If it's a no, well, ¯\_(ツ)_/¯ Professional Crastination (talk) 09:36, 16 July 2024 (UTC)

Generic

This is now available as a generic medication in Canada, if that's useful information to add. 2607:FEA8:EC5D:C00:7745:64F2:3258:44A (talk) 13:13, 17 August 2024 (UTC)