View source for Lisdexamfetamine

{{Short description|Central nervous system stimulant prodrug}}
{{Distinguish|Levoamphetamine}}
{{Use dmy dates|date=March 2024}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 418022579
| image = Lisdexamfetamine structure.svg
| image_class = skin-invert-image
| width = 200
| alt = 
| caption = 
| image2 = Lisdexamfetamine ball-and-stick model.png
| alt2 = <!-- Clinical data -->
| pronounce = 
| tradename = Vyvanse, Elvanse, Tyvense, others
| Drugs.com = {{drugs.com|monograph|lisdexamfetamine-dimesylate}}
| MedlinePlus = a607047
| DailyMedID = Lisdexamfetamine
| pregnancy_AU = B3
| pregnancy_AU_comment = 
| pregnancy_category = 
| dependency_liability = Moderate<ref name="drugs.com">{{Cite web|url=https://www.drugs.com/medical-answers/adderall-vs-vyvanse-3013810/|title=Adderall vs Vyvanse - What's the difference between them?|website=Drugs.com|access-date=12 March 2022}}</ref><ref name="ReferenceA">{{cite journal | vauthors = Goodman DW | title = Lisdexamfetamine dimesylate (vyvanse), a prodrug stimulant for attention-deficit/hyperactivity disorder | journal = P & T | volume = 35 | issue = 5 | pages = 273–287 | date = May 2010 | pmid = 20514273 | pmc = 2873712 }}</ref>
| addiction_liability = Moderate<ref name="drugs.com"/><ref name="ReferenceA"/>
| routes_of_administration = [[Oral administration|By mouth]]
| class = 
| ATC_prefix = N06
| ATC_suffix = BA12
| ATC_supplemental = <!-- Legal status -->
| legal_AU = S8
| legal_AU_comment = <ref>{{cite web |title=Australian Product Information Vyanse® (Lisdexamfetamine dimesilate) |url=https://www.tga.gov.au/sites/default/files/auspar-lisdexamfetamine-dimesilate-180515-pi.pdf |website=[[Department of Health and Aged Care]] |archive-url=https://web.archive.org/web/20230122165157/https://www.tga.gov.au/sites/default/files/auspar-lisdexamfetamine-dimesilate-180515-pi.pdf |archive-date=22 January 2023 |url-status=live}}</ref>
| legal_BR = Class A3
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=3 August 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023}}</ref>
| legal_CA = 
| legal_CA_comment = Schedule G (CDSA I) <ref>{{cite web | title=Vyvanse Product information | website=[[Health Canada]] | date=15 December 2021 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=98033 | access-date=18 March 2024}}</ref>
| legal_DE = Anlage III
| legal_DE_comment = 
| legal_NZ = Class B
| legal_NZ_comment = 
| legal_UK = Class B
| legal_UK_comment = 
| legal_US = Schedule II
| legal_US_comment = <ref name="Vyvanse FDA label">{{cite web | title=Vyvanse- lisdexamfetamine dimesylate capsule; Vyvanse- lisdexamfetamine dimesylate tablet, chewable | website=DailyMed | date=10 March 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=704e4378-ca83-445c-8b45-3cfa51c1ecad | access-date=19 December 2022}}</ref>
| legal_EU = Rx-only
| legal_EU_comment = <ref>{{cite web|url=https://www.ema.europa.eu/documents/psusa/lisdexamfetamine-list-nationally-authorised-medicinal-products-psusa/00010289/202002_en.pdf|title=List of nationally authorised medicinal products : Active substance(s): lisdexamfetamine : Procedure No. PSUSA/00010289/202002|website=Ema.europa.eu|access-date=12 March 2022}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = SE: Förteckning II<ref>{{cite web |url=https://www.lakemedelsverket.se/sv/sok-lakemedelsfakta/substans/v2va9rlain4srv01/lisdexamfetamindimesilat|title=Lisdexamfetamindimesilat|access-date=23 January 2025}}</ref>

<!-- Pharmacokinetic data -->| bioavailability = [[Oral administration|Oral]]: 96.4%<ref>{{cite web| title=Public Assessment Report Decentralised Procedure | url=http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con261790.pdf | archive-url=https://web.archive.org/web/20140826115717/http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con261790.pdf|archive-date=26 August 2014|publisher=MHRA |access-date=23 August 2014 | page=14}}</ref>
| protein_bound = 20% (as [[dextroamphetamine]])<ref name="Drugbank-amph">{{cite DrugBank|drug=Amphetamine|id=DB00182}}</ref>
| metabolism = [[Hydrolysis]] by enzymes in [[red blood cell]]s initially, subsequent metabolism follows
| metabolites = [[Dextroamphetamine]] (and its metabolites) and [[lysine|<small>L</small>-lysine]]
| onset = [[Oral administration|Oral]]: <2&nbsp;hours<ref name="Millichap: onset, peak, and duration">{{cite book | vauthors = Millichap JG |  veditors = Millichap JG | title = Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD | year = 2010 | publisher = Springer | location = New York, USA | isbn = 978-1-4419-1396-8 | pages = 112 | edition = 2nd | chapter = Chapter 9: Medications for ADHD | quote = <br />Table 9.2 Dextroamphetamine formulations of stimulant medication<br />Dexedrine [Peak:2–3&nbsp;h] [Duration:5–6&nbsp;h]&nbsp;...<br />Adderall [Peak:2–3&nbsp;h] [Duration:5–7&nbsp;h]<br />Dexedrine spansules [Peak:7–8&nbsp;h] [Duration:12&nbsp;h]&nbsp;...<br />Adderall XR [Peak:7–8&nbsp;h] [Duration:12&nbsp;h]<br />Vyvanse [Peak:3–4&nbsp;h] [Duration:12&nbsp;h]}}</ref><ref name="XR onset-duration">{{cite journal | vauthors = Brams M, Mao AR, Doyle RL | title = Onset of efficacy of long-acting psychostimulants in pediatric attention-deficit/hyperactivity disorder | journal = Postgraduate Medicine | volume = 120 | issue = 3 | pages = 69–88 | date = September 2008 | pmid = 18824827 | doi = 10.3810/pgm.2008.09.1909 | quote = Onset of efficacy was earliest for d-MPH-ER at 0.5 hours, followed by d, l-MPH-LA at 1 to 2 hours, MCD at 1.5 hours, d, l-MPH-OR at 1 to 2 hours, MAS-XR at 1.5 to 2 hours, MTS at 2 hours, and LDX at approximately 2 hours.&nbsp;... MAS-XR, and LDX have a long duration of action at 12 hours postdose | s2cid = 31791162 }}</ref>
| elimination_half-life = Lisdexamfetamine: <1&nbsp;hour<ref name="pmid27021968" /><br />Dextroamphetamine: 10–12&nbsp;h<ref name="pmid27021968" /><ref name="Vyvanse FDA label" />
| duration_of_action = 10–14&nbsp;hours<ref name="Stahl's Essential Psychopharmacology - Lisdexamfetamine">{{cite book | vauthors=Stahl SM | title=Prescriber's Guide: Stahl's Essential Psychopharmacology | date=March 2017 | publisher=Cambridge University Press | location=Cambridge, United Kingdom | isbn=978-1-108-22874-9 | pages=379–384 | edition=6th | chapter=Lisdexamfetamine }}</ref><ref name="Millichap: onset, peak, and duration" /><ref name="XR onset-duration" />
| excretion = [[Kidney]]: ~2%

<!-- Identifiers -->| index2_label = as salt
| CAS_number_Ref = {{cascite|correct|IUPHAR}}
| CAS_number = 608137-32-2
| CAS_supplemental = 
| PubChem = 11597698
| IUPHAR_ligand = 7213
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01255
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 9772458
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = H645GUL8KJ
| KEGG = D08130
| KEGG2 = D04747
| ChEBI = 
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1201222
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = <small>L</small>-Lysine-d-amphetamine; (2''S'')-2,6-Diamino-''N''-[(2''S'')-1-phenylpropan-2-yl]hexanamide<br />''N''-[(2''S'')-1-Phenyl-2-propanyl]-<small>L</small>-lysinamide

<!-- Chemical data -->| IUPAC_name = (2''S'')-2,6-Diamino-''N''-[(1''S'')-1-methyl-2-phenylethyl]hexanamide
| C = 15
| H = 25
| N = 3
| O = 1
| chirality = [[Dextrorotatory]] [[enantiomer]]
| SMILES = O=C(N[C@H](Cc1ccccc1)C)[C@@H](N)CCCCN
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C15H25N3O/c1-12(11-13-7-3-2-4-8-13)18-15(19)14(17)9-5-6-10-16/h2-4,7-8,12,14H,5-6,9-11,16-17H2,1H3,(H,18,19)/t12-,14-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = VOBHXZCDAVEXEY-JSGCOSHPSA-N

<!-- Physical data -->| density = 
| density_notes = 
| melting_point = 
| melting_high = 
| melting_notes = 
| boiling_point = 
| boiling_notes = 
| solubility = 
| sol_units = 
| specific_rotation = 
}}

<!-- Definition and medical uses -->
'''Lisdexamfetamine''', sold under the brand names '''Vyvanse''' and '''Elvanse''' among others, is a [[stimulant]] medication that is used as a treatment for [[attention deficit hyperactivity disorder]] (ADHD) in children and adults and for moderate-to-severe [[binge eating disorder]] in adults.<ref name=AHFS2019/> Lisdexamfetamine is taken [[by mouth]]. Its effects generally begin within 90 minutes and last for up to 14 hours.<ref name=AHFS2019/>

<!-- Mechanism and chemistry -->
Common side effects of lisdexamfetamine include [[Anorexia (symptom)|loss of appetite]], [[anxiety]], [[diarrhea]], [[insomnia|trouble sleeping]], [[irritability]], and [[nausea]].<ref name="AHFS2019" /> Rare but serious side effects include [[mania]], [[sudden cardiac death]] in those with [[cardiovascular disease|underlying heart problems]], and [[stimulant psychosis|psychosis]].<ref name=AHFS2019/> It has a high potential for [[substance abuse]].<ref name="Vyvanse FDA label" /><ref name=AHFS2019/> [[Serotonin syndrome]] may occur if used with certain other medications.<ref name=AHFS2019/> Its use during [[pregnancy]] may result in harm to the baby and use during [[breastfeeding]] is not recommended by the manufacturer.<ref name="BNF76">{{cite book |title=British national formulary: BNF 76 |date=2018 |publisher=Pharmaceutical Press |isbn=978-0-85711-338-2 |edition=76 |pages=348–349}}</ref><ref name=AHFS2019/><ref name="Drugs.com pregnancy">{{cite web |title=Lisdexamfetamine (Vyvanse) Use During Pregnancy |url=https://www.drugs.com/pregnancy/lisdexamfetamine.html |website=Drugs.com |access-date=16 April 2019 }}</ref>

Lisdexamfetamine is an inactive [[prodrug]] that works after being converted by the body into [[dextroamphetamine]], a [[central nervous system]] (CNS) [[stimulant]].<ref name=AHFS2019/><ref name=Amp2013>{{cite journal | vauthors = Heal DJ, Smith SL, Gosden J, Nutt DJ | title = Amphetamine, past and present--a pharmacological and clinical perspective | journal = Journal of Psychopharmacology | volume = 27 | issue = 6 | pages = 479–496 | date = June 2013 | pmid = 23539642 | pmc = 3666194 | doi = 10.1177/0269881113482532 }}</ref> Chemically, lisdexamfetamine is [[codrug|composed of]] the [[amino acid]] [[Lysine|<small>L</small>-lysine]], [[covalently bonded|attached to]] dextroamphetamine.<ref name="pmid17407369">{{cite journal | vauthors = Blick SK, Keating GM | title = Lisdexamfetamine | journal = Paediatric Drugs | volume = 9 | issue = 2 | pages = 129–135; discussion 136–138 | date = 2007 | pmid = 17407369 | doi = 10.2165/00148581-200709020-00007 | s2cid = 260863254 }}</ref>

<!-- Society and culture -->
Lisdexamfetamine was approved for medical use in the United States in 2007 and in the European Union in 2012.<ref name=AHFS2019>{{cite web |title=Lisdexamfetamine Dimesylate Monograph for Professionals |url=https://www.drugs.com/monograph/lisdexamfetamine-dimesylate.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=15 April 2019 }}</ref><ref>{{cite news |title=Shire's ADHD amphetamine wins British backing
|url=https://www.reuters.com/article/us-shire-adhd-idUKBRE8BH0X820121218/ |date=12 December 2012 |work=Reuters |access-date=14 December 2023 }}</ref> In 2022, it was the 69th most commonly prescribed medication in the United States, with more than 9{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Lisdexamfetamine Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Lisdexamfetamine | access-date = 30 August 2024 }}</ref> It is a [[Controlled Drug in the United Kingdom#Schedule 2 - CD|Class B controlled substance]] in the United Kingdom, a [[Standard for the Uniform Scheduling of Medicines and Poisons#Schedule 8|Schedule 8 controlled drug]] in Australia, and a [[Schedule II controlled substance]] in the United States.<ref name=BNF76/><ref name=DEA2017>{{cite book |title=Drugs of Abuse |date=2017 |publisher=Drug Enforcement Administration • U.S. Department of Justice |page=22 |url=https://www.dea.gov/sites/default/files/2018-06/drug_of_abuse.pdf |access-date=16 April 2019}}</ref>
{{TOC limit}}

== Uses ==
<!-- Part of this section is transcluded from the Amphetamine article - please edit that article or make a request on Talk:Amphetamine to change the text here. -->

=== Medical ===
[[File:30mg Vyvanse capsules.JPG|thumb|30mg Vyvanse capsules]]
{{transcluded section|source=amphetamine|part=yes}}
Lisdexamfetamine is used primarily as a treatment for [[attention deficit hyperactivity disorder]] (ADHD) and [[binge eating disorder]].<ref name="Vyvanse FDA label" /> It has similar {{nowrap|[[off-label]]}} uses as those of other pharmaceutical amphetamines,<ref name="Stahl's Essential Psychopharmacology - Lisdexamfetamine" /> such as the treatment of [[narcolepsy]].<ref name="pmid31859793">{{cite journal | vauthors = Aguilar AC, Frange C, Pimentel Filho LH, Reis MJ, Tufik S, Coelho FM | title = Lisdexamfetamine to improve excessive daytime sleepiness and weight management in narcolepsy: a case series | journal = Brazilian Journal of Psychiatry | volume = 43 | issue = 3 | pages = 314–316 | date = 2020 | pmid = 31859793 | pmc = 7236164 | doi = 10.1590/1516-4446-2019-0544 }}</ref> Individuals over the age of 65 were not commonly tested in clinical trials of lisdexamfetamine for ADHD.<ref name="Vyvanse FDA label" /> According to a 2019 systematic review, lisdexamfetamine was the most effective treatment for [[adult ADHD]].<ref>{{cite journal | vauthors = Stuhec M, Lukić P, Locatelli I | title = Efficacy, Acceptability, and Tolerability of Lisdexamfetamine, Mixed Amphetamine Salts, Methylphenidate, and Modafinil in the Treatment of Attention-Deficit Hyperactivity Disorder in Adults: A Systematic Review and Meta-analysis | journal = The Annals of Pharmacotherapy | volume = 53 | issue = 2 | pages = 121–133 | date = February 2019 | pmid = 30117329 | doi = 10.1177/1060028018795703 | s2cid = 52019992 }}</ref>
{{trim|{{#section-h:Amphetamine|Medical}}}}

=== Enhancing performance ===
{{transcluded section|source=Amphetamine}}
{{trim|{{#section-h:Amphetamine|Enhancing performance}}}}

=== Available forms ===
Lisdexamfetamine is available as the [[mesylate|dimesylate]] [[salt (chemistry)|salt]] in the form of both [[oral administration|oral]] [[capsule (pharmacy)|capsule]]s and chewable [[tablet (pharmacy)|tablet]]s.<ref name="Vyvanse FDA label" /> A dose of 50&nbsp;mg of lisdexamfetamine dimesylate is approximately [[equimolar]] to a 20&nbsp;mg dose of [[dextroamphetamine sulfate]] or to 15&nbsp;mg dextroamphetamine free-base in terms of the amount of [[dextroamphetamine]] contained.<ref name="pmid27021968">{{cite journal | vauthors = Ermer JC, Pennick M, Frick G | title = Lisdexamfetamine Dimesylate: Prodrug Delivery, Amphetamine Exposure and Duration of Efficacy | journal = Clinical Drug Investigation | volume = 36 | issue = 5 | pages = 341–356 | date = May 2016 | pmid = 27021968 | pmc = 4823324 | doi = 10.1007/s40261-015-0354-y }}</ref><ref name="pmid28936175" /><ref name="EMC-SmPC-Elvanse">{{cite web | title = Elvanse Adult 30mg Hard Capsules | url = https://www.medicines.org.uk/emc/product/6828/smpc | access-date = 26 February 2022 | quote = 2. Qualitative and quantitative composition. 30 mg Capsules: Each capsule contains 30 mg lisdexamfetamine dimesylate, equivalent to 8.9 mg of dexamfetamine. 50 mg Capsules: Each capsule contains 50 mg lisdexamfetamine dimesylate, equivalent to 14.8 mg of dexamfetamine. 70 mg Capsules: Each capsule contains 70 mg lisdexamfetamine dimesylate, equivalent to 20.8 mg of dexamfetamine.}}</ref> Lisdexamfetamine capsules can be swallowed intact, or they can be opened and mixed into water, yogurt, or applesauce and consumed in that manner.<ref name="Vyvanse FDA label" /><ref name="pmid27661399">{{cite journal | vauthors = Ermer J, Corcoran M, Lasseter K, Martin PT | title = Relative Bioavailabilities of Lisdexamfetamine Dimesylate and D-Amphetamine in Healthy Adults in an Open-Label, Randomized, Crossover Study After Mixing Lisdexamfetamine Dimesylate With Food or Drink | journal = Ther Drug Monit | volume = 38 | issue = 6 | pages = 769–776 | date = December 2016 | pmid = 27661399 | pmc = 5158093 | doi = 10.1097/FTD.0000000000000343 }}</ref>

== Contraindications ==
Pharmaceutical lisdexamfetamine is [[contraindication|contraindicated]] in people with [[hypersensitivity]] to amphetamine products or any of the formulation's [[inactive ingredients]].<ref name="Vyvanse FDA label" /> It is also contraindicated in patients who have used a [[monoamine oxidase inhibitor]] (MAOI) within the last 14&nbsp;days.<ref name="Vyvanse FDA label" /><ref name="International">{{cite web | vauthors = Heedes G, Ailakis J | title=Amphetamine (PIM 934) | url=http://www.inchem.org/documents/pims/pharm/pim934.htm | website=INCHEM | publisher=International Programme on Chemical Safety | access-date=24 June 2014 }}</ref> Amphetamine products are contraindicated by the [[United States Food and Drug Administration]] (USFDA) in people with a history of [[drug abuse]], [[heart disease]], or severe [[Irritability|agitation]] or anxiety, or in those currently experiencing [[arteriosclerosis]], [[glaucoma]], [[hyperthyroidism]], or severe [[hypertension]].<ref name="FDA Adderall XR label" /> However, a [[Europe]]an [[medical consensus|consensus statement]] on adult ADHD noted that stimulants do not worsen substance misuse in adults with ADHD and comorbid [[substance use disorder]] and should not be avoided in these individuals.<ref name="pmid30453134">{{cite journal | vauthors = Kooij JJ, Bijlenga D, Salerno L, Jaeschke R, Bitter I, Balázs J, Thome J, Dom G, Kasper S, Nunes Filipe C, Stes S, Mohr P, Leppämäki S, Casas M, Bobes J, Mccarthy JM, Richarte V, Kjems Philipsen A, Pehlivanidis A, Niemela A, Styr B, Semerci B, Bolea-Alamanac B, Edvinsson D, Baeyens D, Wynchank D, Sobanski E, Philipsen A, McNicholas F, Caci H, Mihailescu I, Manor I, Dobrescu I, Saito T, Krause J, Fayyad J, Ramos-Quiroga JA, Foeken K, Rad F, Adamou M, Ohlmeier M, Fitzgerald M, Gill M, Lensing M, Motavalli Mukaddes N, Brudkiewicz P, Gustafsson P, Tani P, Oswald P, Carpentier PJ, De Rossi P, Delorme R, Markovska Simoska S, Pallanti S, Young S, Bejerot S, Lehtonen T, Kustow J, Müller-Sedgwick U, Hirvikoski T, Pironti V, Ginsberg Y, Félegyházy Z, Garcia-Portilla MP, Asherson P | title = Updated European Consensus Statement on diagnosis and treatment of adult ADHD | journal = European Psychiatry | volume = 56 | issue = | pages = 14–34 | date = February 2019 | pmid = 30453134 | doi = 10.1016/j.eurpsy.2018.11.001 | s2cid = 53714228 | doi-access = free | hdl = 10067/1564410151162165141 | hdl-access = free }}</ref> In any case, the statement noted that immediate-release stimulants should be avoided in those with both ADHD and substance use disorder and that slower-release stimulant formulations like {{Abbrlink|OROS|osmotic-controlled release oral delivery system}} [[methylphenidate]] (Concerta) and lisdexamfetamine should be preferred due to their lower misuse potential.<ref name="pmid30453134" /> Prescribing information approved by the Australian [[Therapeutic Goods Administration]] further contraindicates [[anorexia nervosa|anorexia]].<ref>{{cite web|title=Dexamphetamine tablets|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-00828-3|website=Therapeutic Goods Administration|access-date=12 April 2014}}</ref>

== Adverse effects ==
Products containing lisdexamfetamine have a comparable [[drug safety]] profile to those containing [[amphetamine]].<ref name="pmid17407369" /> The major [[side effect]]s of lisdexamfetamine in short-term [[clinical trial]]s (≥5% incidence) have included [[decreased appetite]], [[insomnia]], [[dry mouth]], [[weight loss]], [[irritability]], [[upper abdominal pain]], [[nausea]], [[vomiting]], [[diarrhea]], [[constipation]], [[increased heart rate]], [[anxiety]], [[dizziness]], and [[feeling jittery]].<ref name="Vyvanse FDA label" /><ref name="AHFS2019" /> Rates of side effects may vary in adults, adolescents, and children.<ref name="Vyvanse FDA label" /> Rare but serious side effects of lisdexamfetamine may include [[mania]], [[sudden cardiac death]] in those with [[cardiovascular disease|underlying heart problems]], [[stimulant psychosis]], and [[serotonin syndrome]].<ref name=AHFS2019/><ref name="Vyvanse FDA label" />

== Interactions ==
* [[Acidifiers|Acidifying agents]]: Drugs or foods that acidify the urine, such as [[ascorbic acid]], increase urinary excretion of dextroamphetamine, thus decreasing the [[half-life]] and effectiveness of dextroamphetamine in the body.<ref name="Vyvanse FDA label" /><ref name="FDA Adderall XR label" />
* [[Alkalinizing agent]]s: Drugs or foods that alkalinize the urine, such as [[sodium bicarbonate]], decrease urinary excretion of dextroamphetamine, thus increasing the half-life and effectiveness of dextroamphetamine in the body.<ref name="Vyvanse FDA label" /><ref name="FDA Adderall XR label" />
* [[CYP2D6 inhibitor]]s: [[Hydroxylation]] via the [[cytochrome P450]] enzyme [[CYP2D6]] is the major pathway of [[metabolism]] of dextroamphetamine.<ref name="pmid31776871">{{cite journal | vauthors = Schoretsanitis G, de Leon J, Eap CB, Kane JM, Paulzen M | title = Clinically Significant Drug-Drug Interactions with Agents for Attention-Deficit/Hyperactivity Disorder | journal = CNS Drugs | volume = 33 | issue = 12 | pages = 1201–1222 | date = December 2019 | pmid = 31776871 | doi = 10.1007/s40263-019-00683-7 | s2cid = 208330108 }}</ref> Potent CYP2D6 inhibitors, such as [[paroxetine]], [[fluoxetine]], [[bupropion]], and [[duloxetine]], among others, may inhibit the metabolism of dextroamphetamine and thereby increase exposure to it.<ref name="pmid31776871"/><ref name="Vyvanse FDA label" /> Studies characterizing this potential interaction are currently lacking.<ref name="pmid31776871" /> Concomitant use of lisdexamfetamine with CYP2D6 inhibitors may increase the risk of [[serotonin syndrome]] due to greater drug exposure.<ref name="Vyvanse FDA label" />
* [[Monoamine oxidase inhibitor]]s: Concomitant use of MAOIs and central nervous system stimulants such as lisdexamfetamine can cause a hypertensive crisis.<ref name="Vyvanse FDA label" />
* [[Norepinephrine reuptake inhibitor]]s (NRIs) like [[atomoxetine]] prevent [[norepinephrine]] release induced by amphetamines and have been found to reduce the [[stimulant]], [[euphoriant]], and [[sympathomimetic]] effects of [[dextroamphetamine]] in humans.<ref name="TreuerGauMéndez2013">{{cite journal | vauthors = Treuer T, Gau SS, Méndez L, Montgomery W, Monk JA, Altin M, Wu S, Lin CC, Dueñas HJ | title = A systematic review of combination therapy with stimulants and atomoxetine for attention-deficit/hyperactivity disorder, including patient characteristics, treatment strategies, effectiveness, and tolerability | journal = J Child Adolesc Psychopharmacol | volume = 23 | issue = 3 | pages = 179–193 | date = April 2013 | pmid = 23560600 | pmc = 3696926 | doi = 10.1089/cap.2012.0093 | url = }}</ref><ref name="HealSmithFindling2012">{{cite book | vauthors = Heal DJ, Smith SL, Findling RL | title = Behavioral Neuroscience of Attention Deficit Hyperactivity Disorder and Its Treatment | chapter = ADHD: current and future therapeutics | series = Current Topics in Behavioral Neurosciences | volume = 9 | pages = 361–390 | date = 2012 | pmid = 21487953 | doi = 10.1007/7854_2011_125 | isbn = 978-3-642-24611-1 | chapter-url = | quote = Adjunctive therapy with DL-methylphenidate in atomoxetine partial responders has been successful (Wilens et al. 2009), but this also increases the rates of insomnia, irritability and loss of appetite (Hammerness et al. 2009). This combination therapy has not included amphetamine because blockade of NET by atomoxetine prevents entry of amphetamine into presynaptic noradrenergic terminals (Sofuoglu et al. 2009). }}</ref><ref name="SofuogluPolingHill2009">{{cite journal | vauthors = Sofuoglu M, Poling J, Hill K, Kosten T | title = Atomoxetine attenuates dextroamphetamine effects in humans | journal = Am J Drug Alcohol Abuse | volume = 35 | issue = 6 | pages = 412–416 | date = 2009 | pmid = 20014909 | pmc = 2796580 | doi = 10.3109/00952990903383961 | url = }}</ref>

== Pharmacology ==
{{hatnote|Main section: {{section link|Amphetamine|Pharmacodynamics}}}}

=== Mechanism of action ===
{{amphetamine pharmacodynamics}}
Lisdexamfetamine is an [[inactive prodrug]] that is converted in the body to dextroamphetamine, a pharmacologically active compound that is responsible for the drug's activity.<ref name="Vyvanse" /> After oral ingestion, lisdexamfetamine is broken down by enzymes in red blood cells to form [[lysine|<small>L</small>-lysine]], a naturally occurring essential amino acid, and dextroamphetamine.<ref name="Vyvanse FDA label" /> The half-life of this conversion is roughly 1 hour. The conversion of lisdexamfetamine to dextroamphetamine is not affected by gastrointestinal [[pH]] and is unlikely to be affected by alterations in normal gastrointestinal transit times.<ref name="Vyvanse FDA label" /><ref name="Jasinski 2009" /> Studies show a linear relationship between peak plasma concentration of dextroamphetamine and lisdexamfetamine dose up to lisdexamfetamine doses of 250&nbsp;mg.<ref>{{cite journal | vauthors = Ermer J, Homolka R, Martin P, Buckwalter M, Purkayastha J, Roesch B | title = Lisdexamfetamine dimesylate: linear dose-proportionality, low intersubject and intrasubject variability, and safety in an open-label single-dose pharmacokinetic study in healthy adult volunteers | journal = Journal of Clinical Pharmacology | volume = 50 | issue = 9 | pages = 1001–1010 | date = September 2010 | pmid = 20173084 | doi = 10.1177/0091270009357346 }}</ref>

The [[enantiomers|optical isomers]] of [[amphetamine]], i.e., [[dextroamphetamine]] and [[levoamphetamine]], are [[TAAR1 agonist]]s and [[vesicular monoamine transporter 2]] inhibitors that can enter [[monoamine]] neurons;<ref name="Miller">{{cite journal | vauthors = Miller GM | title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity | journal = Journal of Neurochemistry | volume = 116 | issue = 2 | pages = 164–176 | date = January 2011 | pmid = 21073468 | pmc = 3005101 | doi = 10.1111/j.1471-4159.2010.07109.x }}</ref><ref name="E Weihe">{{cite journal | vauthors = Eiden LE, Weihe E | title = VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse | journal = Annals of the New York Academy of Sciences | volume = 1216 | issue = 1 | pages = 86–98 | date = January 2011 | pmid = 21272013 | pmc = 4183197 | doi = 10.1111/j.1749-6632.2010.05906.x | quote = VMAT2 is the CNS vesicular transporter for not only the biogenic amines DA, NE, EPI, 5-HT, and HIS, but likely also for the trace amines TYR, PEA, and thyronamine (THYR)&nbsp;... [Trace aminergic] neurons in mammalian CNS would be identifiable as neurons expressing VMAT2 for storage, and the biosynthetic enzyme aromatic amino acid decarboxylase (AADC). | bibcode = 2011NYASA1216...86E }}</ref> this allows them to release monoamine [[neurotransmitter]]s ([[dopamine]], [[norepinephrine]], and [[serotonin]], among others) from their [[synaptic vesicles|storage sites]] in the [[presynaptic neuron]], as well as prevent the [[reuptake|reuptake of these neurotransmitters]] from the [[synaptic cleft]].<ref name="Miller" /><ref name="E Weihe" />

Lisdexamfetamine was developed to provide a long-duration effect that is consistent throughout the day, with reduced potential for abuse. The attachment of the amino acid lysine slows down the relative amount of dextroamphetamine available in the bloodstream. Because no free dextroamphetamine is present in lisdexamfetamine capsules, dextroamphetamine does not become available through mechanical manipulation, such as crushing or simple extraction. A relatively sophisticated biochemical process is needed to produce dextroamphetamine from lisdexamfetamine.<ref name="Jasinski 2009"/> As opposed to [[Adderall]], which contains amphetamine salts in a 3:1 dextro:levo ratio, lisdexamfetamine is a single-[[enantiomer]] dextroamphetamine formula.<ref name="Vyvanse">{{cite DrugBank|id= DB01255|drug=Lisdexamfetamine}}</ref><ref name="FDA Adderall XR label">{{cite web | title=Adderall XR- dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine sulfate and amphetamine aspartate capsule, extended release | website=DailyMed | date=25 October 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aff45863-ffe1-4d4f-8acf-c7081512a6c0 | access-date=18 March 2024}}</ref> Studies conducted show that lisdexamfetamine dimesylate may have less abuse potential than dextroamphetamine and an abuse profile similar to [[diethylpropion]] at dosages that are FDA-approved for treatment of [[attention deficit hyperactivity disorder|ADHD]], but still has a high abuse potential when this dosage is exceeded by over 100%.<ref name="Jasinski 2009">{{cite journal | vauthors = Jasinski DR, Krishnan S | title = Abuse liability and safety of oral lisdexamfetamine dimesylate in individuals with a history of stimulant abuse | journal = Journal of Psychopharmacology | volume = 23 | issue = 4 | pages = 419–427 | date = June 2009 | pmid = 19329547 | doi = 10.1177/0269881109103113 | s2cid = 6138292 }}</ref>

=== Pharmacokinetics ===
[[File:Dextroamphetamine concentration-time curves after oral administration of equimolar doses of dextroamphetamine and lisdexamfetamine in adults.png|class=skin-invert-image|thumb|right|400px|Dextroamphetamine concentrations after oral administration of a single equimolar dose of dextroamphetamine sulfate immediate-release (IR) (40 mg; equivalent to 30 mg dextroamphetamine free-base) and lisdexamfetamine dimesylate (100 mg) in healthy adults.<ref name="pmid28936175" /><ref name="pmid30381248">{{cite journal | vauthors = Strajhar P, Vizeli P, Patt M, Dolder PC, Kratschmar DV, Liechti ME, Odermatt A | title = Effects of lisdexamfetamine on plasma steroid concentrations compared with d-amphetamine in healthy subjects: A randomized, double-blind, placebo-controlled study | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 186 | issue = | pages = 212–225 | date = February 2019 | pmid = 30381248 | doi = 10.1016/j.jsbmb.2018.10.016 | s2cid = 53183893 | url = https://edoc.unibas.ch/69588/1/20190220112204_5c6d2a4cdf9fd.pdf }}</ref> [[Cmax (pharmacology)|C<sub>max</sub>]], [[elimination half-life|t<sub>1/2</sub>]], and [[Area under the curve (pharmacokinetics)|AUC<sub>∞</sub>]] were all similar between the two drugs, while [[tlag (pharmacokinetics)|t<sub>lag</sub>]] (1.5 hours vs. 0.8 hours) and [[Tmax (pharmacology)|t<sub>max</sub>]] (4.6 hours vs. 3.3 hours) were longer for lisdexamfetamine than with dextroamphetamine.<ref name="pmid28936175" />]]
{{transcluded section|source=Amphetamine}}
{{trim|{{#section-h:Amphetamine|Pharmacokinetics}}}}

== Chemistry ==
Lisdexamfetamine is a [[substituted amphetamine]] with an [[amide]] linkage formed by the [[condensation reaction|condensation]] of [[dextroamphetamine]] with the [[carboxylic acid|carboxylate group]] of the [[essential amino acid]] [[Lysine|<small>L</small>-lysine]].<ref name="pmid17407369" /> The reaction occurs with retention of [[stereochemistry]], so the product lisdexamfetamine exists as a single [[stereoisomer]]. There are many possible names for lisdexamfetamine based on [[IUPAC nomenclature]], but it is usually named as {{nowrap|''N''-[(2''S'')-1-phenyl-2-propanyl]-<small>L</small>-lysinamide}} or {{nowrap|(2''S'')-2,6-diamino-''N''-[(1''S'')-1-methyl-2-phenylethyl]hexanamide}}.<ref name = ChemSpider>{{cite web|year = 2015|title = Lisdexamfetamine|url = http://www.chemspider.com/Chemical-Structure.9772458.html|website = [[ChemSpider]]|publisher = [[Royal Society of Chemistry]]|access-date = 22 April 2019}}</ref> The condensation reaction occurs with loss of water:

:[[dextroamphetamine|(''S'')-{{chem|PhCH|2|CH(CH|3|)NH|2}}]] &nbsp; + &nbsp; [[lysine|(''S'')-{{chem|HOOCCH(NH|2|)CH|2|CH|2|CH|2|CH|2|NH|2}}]] &nbsp; → &nbsp; (''S'',''S'')-{{chem|PhCH|2|CH(CH|3|)NHC(O)CH(NH|2|)CH|2|CH|2|CH|2|CH|2|NH|2}} &nbsp; + &nbsp; {{chem|H|2|O}}

[[Amine]] [[functional group]]s are vulnerable to oxidation in air and so pharmaceuticals containing them are usually formulated as [[salt (chemistry)|salts]] where this [[moiety (chemistry)|moiety]] has been [[protonated]]. This increases stability, water solubility, and, by converting a [[molecular compound]] to an [[ionic compound]], increases the melting point and thereby ensures a solid product.<ref>{{cite book| veditors = Stahl PH, Wermuth DG |editor-link2 = Camille G. Wermuth |title = Pharmaceutical Salts: Properties, Selection, and Use|edition = 2nd|publisher = [[John Wiley & Sons]]|year = 2011|isbn = 978-3-906390-51-2}}</ref> In the case of lisdexamfetamine, this is achieved by reacting with two equivalents of [[methanesulfonic acid]] to produce the di[[mesylate]] salt, a [[water-soluble]] (792&nbsp;mg&nbsp;mL<sup>−1</sup>) powder with a white to off-white color.<ref name="Vyvanse FDA label" />

:{{chem|PhCH|2|CH(CH|3|)NHC(O)CH(NH|2|)CH|2|CH|2|CH|2|CH|2|NH|2}} &nbsp; + &nbsp; 2&nbsp;[[methanesulfonic acid|{{chem|CH|3|SO|3|H}}]] &nbsp; → &nbsp; {{chem|[PhCH|2|CH(CH|3|)NHC(O)CH(NH|3|+|)CH|2|CH|2|CH|2|CH|2|NH|3|+|]}}{{chem|[CH|3|SO|3|-|]|2}}

=== Comparison to other formulations ===
Lisdexamfetamine dimesylate is one marketed formulation delivering dextroamphetamine. The following table compares the drug to other amphetamine pharmaceuticals.

{{Amphetamine base in marketed amphetamine medications}}

== History ==
{{See also|History and culture of substituted amphetamines}}

Lisdexamfetamine was [[drug development|developed]] by [[Robert Oberlender]] at New River Pharmaceuticals, under the name NRP104, before being bought by [[Takeda Pharmaceuticals]] through its acquisition of [[Shire Pharmaceuticals]], prior to market release.<ref>{{Cite web |title=Robert A. Oberlender, PhD |url=https://www.michaeljfox.org/researcher/robert-oberlender-phd |access-date=2025-02-17 |website=Michael J. Fox Foundation |language=en}}</ref> It was developed to create a longer-lasting and less-easily abused version of dextroamphetamine, as the requirement of conversion into dextroamphetamine via enzymes in the [[red blood cells]] delays its onset of action, regardless of the route of administration.<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 | url-access = subscription }}</ref>

In February 2007, the US [[Food and Drug Administration]] (FDA) approved lisdexamfetamine for the treatment of ADHD.<ref name="FDAAdultApproval">{{cite web | title=Drug Approval Package: Vyvanse (Lisdexamfetamine Dimesylate) NDA #021977 | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021977s000TOC.cfm | access-date=18 March 2024}}</ref> In August 2009, [[Health Canada]] approved the marketing of lisdexamfetamine for prescription use.<ref>{{cite web | title=Summary Basis of Decision (SBD) for Vyvanse | website=[[Health Canada]] | date=10 June 2010 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailOne.php?linkID=SBD00311 | access-date=18 March 2024}}</ref>

In January 2015, lisdexamfetamine was approved by the FDA for the treatment of [[binge eating disorder]] in adults.<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>

The FDA gave tentative approval to [[generic drug|generic formulation]]s of lisdexamfetamine in 2015.<ref name="FDA2015">{{Cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/202802Orig1s000TAltr.pdf|title=Tentative approval|date=3 March 2023|access-date=24 April 2022|archive-date=3 March 2023|archive-url=https://web.archive.org/web/20230303055201/https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/202802Orig1s000TAltr.pdf|url-status=dead}}</ref> The expiration date for [[patent protection]] of lisdexamfetamine in the US was 24 February 2023.<ref name="FDA2015" /> The Canadian patent expired 20 years from the filing date of 1 June 2004.<ref>{{Cite web |title=Canadian Patent Database / Base de données sur les brevets canadiens |url=https://www.ic.gc.ca/opic-cipo/cpd/eng/patent/2527646/summary.html |access-date=4 May 2023 |website=www.ic.gc.ca }}</ref>

Production quotas for 2016 in the United States were 29,750&nbsp;kg.<ref>{{cite web |title=DEA Office of Diversion Control |url=http://www.deadiversion.usdoj.gov/quotas/quota_history.pdf |url-status=dead |archive-url=https://web.archive.org/web/20160527045141/http://www.deadiversion.usdoj.gov/quotas/quota_history.pdf |archive-date=27 May 2016 |access-date=7 November 2023 |publisher=DEA}}</ref>

== Society and culture ==

=== Name ===
[[Image:Elvanse.jpg|thumb|Elvanse Adult capsules 50mg and 70mg laid on the packaging (German)]]

''Lisdexamfetamine'' is the [[International Nonproprietary Name]] (INN) and is a contraction of [[lysine|<small>L</small>-lysine]]-[[dextroamphetamine]].<ref name="pmid26693882">{{cite journal | vauthors = Buoli M, Serati M, Cahn W | title = Alternative pharmacological strategies for adult ADHD treatment: a systematic review | journal = Expert Review of Neurotherapeutics | volume = 16 | issue = 2 | pages = 131–144 | date = 2016 | pmid = 26693882 | doi = 10.1586/14737175.2016.1135735 | s2cid = 33004517 }}</ref>

As of November 2020, lisdexamfetamine is sold under the following brand names: Aduvanz, Elvanse, Juneve, Samexid, Tyvense, Venvanse, and Vyvanse.<ref>{{cite web |title=Lisdexamfetamine international brands |url=https://www.drugs.com/international/lisdexamfetamine.html |publisher=Drugs.com |access-date=11 November 2020 |archive-url=https://web.archive.org/web/20201111173315/https://www.drugs.com/international/lisdexamfetamine.html |archive-date=11 November 2020 |url-status=dead}}</ref>

== Research ==

=== Depression ===
Amphetamine was used to treat [[depression (mood)|depression]] starting in the 1930s and has been described as the first [[antidepressant]].<ref name="Rasmussen2006">{{cite journal | vauthors = Rasmussen N | title = Making the first anti-depressant: amphetamine in American medicine, 1929-1950 | journal = J Hist Med Allied Sci | volume = 61 | issue = 3 | pages = 288–323 | date = July 2006 | pmid = 16492800 | doi = 10.1093/jhmas/jrj039 | url = }}</ref> In clinical studies in the 1970s and 1980s, psychostimulants, including amphetamine and [[methylphenidate]], were found to transiently improve mood in a majority of people with depression and to increase [[pro-motivational agent|psychomotor activation]] in almost all individuals.<ref name="BrownGershon1993">{{cite journal | vauthors = Brown AS, Gershon S | title = Dopamine and depression | journal = J Neural Transm Gen Sect | volume = 91 | issue = 2–3 | pages = 75–109 | date = 1993 | pmid = 8099801 | doi = 10.1007/BF01245227 | url = }}</ref>

Some clinical trials that used lisdexamfetamine as an [[adjunct therapy|add-on therapy]] with a [[selective serotonin reuptake inhibitor]] (SSRI) or [[serotonin-norepinephrine reuptake inhibitor]] (SNRI) for [[treatment-resistant depression]] indicated that this is no more effective than the use of an SSRI or SNRI alone.<ref name="LDX adjunct therapy">{{cite journal | vauthors = Dale E, Bang-Andersen B, Sánchez C | title = Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs | journal = Biochemical Pharmacology | volume = 95 | issue = 2 | pages = 81–97 | date = May 2015 | pmid = 25813654 | doi = 10.1016/j.bcp.2015.03.011 | doi-access = free }}</ref> Other studies indicated that psychostimulants potentiated antidepressants, and were under-prescribed for treatment-resistant depression. In those studies, patients showed significant improvement in energy, mood, and psychomotor activity.<ref name="Psychostimulants in the therapy of treatment-resistant depression Review of the literature and findings from a retrospective study in 65 depressed patients">{{cite journal | vauthors = Stotz G, Woggon B, Angst J | title = Psychostimulants in the therapy of treatment-resistant depression Review of the literature and findings from a retrospective study in 65 depressed patients | journal = Dialogues in Clinical Neuroscience | volume = 1 | issue = 3 | pages = 165–174 | date = December 1999 | doi = 10.31887/DCNS.1999.1.3/gstotz | pmid = 22034135 | pmc = 3181580 }}</ref> Clinical guidelines advise caution in the use of stimulants for depression and advise them only as [[second-line therapy|second-]] or [[third-line therapy|third-line]] adjunctive agents.<ref name="pmid34986373" />

In February 2014, Shire announced that two late-stage [[clinical trial]]s had found that Vyvanse was not an effective treatment for depression, and development for this indication was discontinued.<ref>{{cite news|url=http://uk.reuters.com/article/shire-vyvanse-idUKL2N0LB28F20140207 |archive-url=https://web.archive.org/web/20160310201117/http://uk.reuters.com/article/shire-vyvanse-idUKL2N0LB28F20140207 |url-status=dead |archive-date=10 March 2016 | vauthors = Hirschler B |title=UPDATE 2-Shire scraps Vyvanse for depression after failed trials|publisher=Reuters |date=7 February 2014 |access-date=13 February 2014}}</ref><ref name="AdisInsight">{{Cite web|url=https://adisinsight.springer.com/drugs/800020876|title=Lisdexamfetamine - Shionogi/Takeda |website=Adisinsight.springer.com|access-date=12 March 2022|quote=Clinical development is underway in the US, for mood disorders in children and adolescents for binge eating disorder and ADHD.}}</ref> A 2018 [[meta-analysis]] of [[randomized controlled trial]]s of lisdexamfetamine for antidepressant augmentation in people with [[major depressive disorder]]—the first to be conducted—found that lisdexamfetamine was not significantly better than placebo in improving [[Montgomery–Åsberg Depression Rating Scale]] scores, [[response rate (medicine)|response rate]]s, or [[remission rate]]s.<ref name="pmid29028590">{{cite journal | vauthors = Giacobbe P, Rakita U, Lam R, Milev R, Kennedy SH, McIntyre RS | title = Efficacy and tolerability of lisdexamfetamine as an antidepressant augmentation strategy: A meta-analysis of randomized controlled trials | journal = Journal of Affective Disorders | volume = 226 | issue = | pages = 294–300 | date = January 2018 | pmid = 29028590 | doi = 10.1016/j.jad.2017.09.041 }}</ref> However, there was indication of a small effect in improving depressive symptoms that approached trend-level significance.<ref name="pmid29028590" /> Lisdexamfetamine was well-tolerated in the meta-analysis.<ref name="pmid29028590" /> The quantity of evidence was limited, with only four trials included.<ref name="pmid29028590" /> In a subsequent 2022 [[network meta-analysis]], lisdexamfetamine was significantly effective as an antidepressant augmentation for treatment-resistant depression.<ref name="pmid34986373">{{cite journal | vauthors = Nuñez NA, Joseph B, Pahwa M, Kumar R, Resendez MG, Prokop LJ, Veldic M, Seshadri A, Biernacka JM, Frye MA, Wang Z, Singh B | title = Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis | journal = Journal of Affective Disorders | volume = 302 | issue = | pages = 385–400 | date = April 2022 | pmid = 34986373 | doi = 10.1016/j.jad.2021.12.134 | pmc = 9328668 | s2cid = 245657964 }}</ref>

Although lisdexamfetamine has shown limited effectiveness in the treatment of depression in clinical trials, a [[Phases of clinical research#Phase II|phase II]] [[clinical study]] found that the addition of lisdexamfetamine to an antidepressant improved [[executive dysfunction]] in people with mild major depressive disorder but persisting executive dysfunction.<ref name="PanGrovuMcIntyre2019">{{cite book | title = Translational Medicine in CNS Drug Development | vauthors = Pan Z, Grovu RC, McIntyre RS | chapter = Translational Medicine Strategies in Drug Development for Mood Disorders | series = Handbook of Behavioral Neuroscience | date = 2019 | volume = 29 | pages = 333–347 | publisher = Elsevier | issn = 1569-7339 | doi = 10.1016/B978-0-12-803161-2.00023-0 | isbn = 978-0-12-803161-2 | s2cid = 196561249 }}</ref><ref name="pmid24309905">{{cite journal | vauthors = Madhoo M, Keefe RS, Roth RM, Sambunaris A, Wu J, Trivedi MH, Anderson CS, Lasser R | title = Lisdexamfetamine dimesylate augmentation in adults with persistent executive dysfunction after partial or full remission of major depressive disorder | journal = Neuropsychopharmacology | volume = 39 | issue = 6 | pages = 1388–1398 | date = May 2014 | pmid = 24309905 | pmc = 3988542 | doi = 10.1038/npp.2013.334 }}</ref>

== Explanatory notes ==
{{reflist|group=note}}

== Reference notes ==
{{Reflist|group="sources"}}

== References ==
{{Reflist}}

{{Amphetamine|state=expanded}}
{{Psychostimulants, agents used for ADHD and nootropics}}
{{ADHD pharmacotherapies}}
{{Monoamine releasing agents}}
{{Phenethylamines}}
{{Portal bar|Medicine|Chemistry|Biology}}
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