Lisdexamfetamine: Difference between revisions

[[Subjective effects]] are essentially identical to that of dextroamphetamine except with a slower onset and a longer duration. These include [[stimulation (in a small percent of the population paradoxal sedation)]], [[focus enhancement]], [[motivation enhancement]], [[euphoria]], and in a smaller population . However, unlike dextroamphetamine, lisdexamfetamine was specifically designed to prevent non-oral forms of administration (marketed as an anti-abuse design). This means that [[insufflation]], [[Route of administration#Smoked|smoking]] or [[Route of administration#Injection|injection]] do not provide faster absorption or onset. It is sometimes sold and used illicitly as a "study drug" as well as a recreational substance.  

Despite the marketed anti-abuse design, many users report that lisdexamfetamine is capable of producing dependence and addiction like other [[euphoric]] stimulants, particularly when it is taken above the recommended dosage. As a result, it is highly advised to use [[harm reduction practices]] if using this substance.

Lisdexamfetamine was developed by New River Pharmaceuticals as a longer-lasting and less-easily abused version of [[Amphetamine#Enantiomers|<small>d</small>-amphetamine]] (dextroamphetamine). <ref name="CNS Spectrums">{{cite journal | vauthors = Mattingly G | title = Lisdexamfetamine dimesylate: a prodrug stimulant for the treatment of ADHD in children and adults | journal = CNS Spectrums | volume = 15 | issue = 5 | pages = 315–325 | date = May 2010 | pmid = 20448522 | doi = 10.1017/S1092852900027541 | s2cid = 46435024 | url = https://digitalcommons.wustl.edu/open_access_pubs/3506 }}</ref>

The FDA approved lisdexamfetamine for ADHD treatment in adults on the 23th of April 2008 <ref name="FDAAdultApproval">{{Cite web|url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/021977s001ltr.pdf|title=FDA Adult Approval of Vyvanse – FDA Label and Approval History|website=Accessdate.fda.gov|access-date=12 March 2022}}</ref>, followed by an approval binge eating disorder in adults in January 2015. <ref>{{cite press release | title=FDA expands uses of Vyvanse to treat binge-eating disorder | website=U.S. [[Food and Drug Administration]] (FDA) | date=30 January 2015 | url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm432543.htm | archive-url=https://web.archive.org/web/20180126103215/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm432543.htm | archive-date=26 January 2018 | url-status=dead | access-date=19 March 2023}}</ref>

As a [[prodrug]], lisdexamfetamine is inactive in the form administered. Once ingested, it is enzymatically cleaved into two parts: L-lysine, a naturally occurring essential amino acid, and <small>d</small>-amphetamine, a central nervous system stimulant. Thus lisdexamfetamine functions as an extended release version of dexamphetamine. Because <small>d</small>-amphetamine needs to be liberated from lysine via contact with red blood cells, effects are independent of route of administration. Conversion of lisdexamfetamine into active <small>d</small>-amphetamine is enzymatically [[Rate-Limiting Step|rate-limited]], slowing down the time to achieve peak concentrations and decreasing its magnitude and dampening consequent striatal dopamine release, which is thought to be responsible for its euphoric and [[compulsive redosing]] effects.

While the subjective effects are almost identical to that of [[amphetamine]], lisdexamfetamine is significantly longer in its duration and more consistent in its intensity due to the slow release metabolism. Although this drug is rate-limited in its metabolism, sufficiently high doses are comparable to its instant release counterparts once the peak has been reached.

Addiction is a serious risk with heavy recreational amphetamine use but is unlikely to arise from typical long-term medical use at therapeutic doses. Lisdexamfetamine has been posited to have less potential for abuse and addiction than other pharmaceutical amphetamines due to the slower onset and the self-limiting metabolism, which puts a cap on the maximum peak plasma concentration and consequent dopamine release. Caution is nonetheless advised, as with other drugs in the amphetamine class.  

Tolerance develops rapidly in amphetamine abuse (i.e. a recreational amphetamine overdose), so periods of extended use require increasingly larger doses of the drug in order to achieve the same effect. Repeated use of lisdexamfetamine will result in a gradual tolerance proportional to the dosage taken. Patients prescribed this drug often must increase their dosage after a time to maintain its efficacy.

===Overdose===

A severe amphetamine overdose can result in a [[stimulant psychosis]] that may involve a variety of symptoms, such as paranoia, delusions, and hallucinations, including the infamous [[Shadow people]]. A Cochrane Collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine psychosis states that about 5–15% of users fail to recover completely. According to the same review, there is at least one trial that shows antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis. Psychosis very rarely arises from therapeutic use. The combination of prolonged use of high doses combined with sleep deprivation significantly increases the risk of stimulant psychosis.

*[https://www.drugbank.ca/drugs/DB01255 Lisdexamfetamine (DrugBank)]