Lisdexamfetamine: A Review in ADHD in Adults
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Lisdexamfetamine dimesylate (lisdexamfetamine) is a long-acting amfetamine prodrug with a convenient once-daily oral regimen that offers the potential for improved adherence and reduced abuse compared with short-acting preparations of amfetamines. Lisdexamfetamine (as Elvanse Adult®; Tyvense Adult™) has been approved for use in adults with attention-deficit hyperactivity disorder (ADHD) under the EU decentralization procedure, with the first approvals in the UK, Sweden and Denmark. This approval reflects the results of three short-term trials in adults with ADHD in which fixed- or flexible-dose lisdexamfetamine produced significantly greater improvements than placebo in ADHD symptoms, overall functioning, executive functioning (including in patients with significant pre-existing impairment) and quality of life. Of note, a post hoc analysis of one of these studies suggested that the response to lisdexamfetamine was generally similar in treatment-naïve patients and those who had already received—and not responded satisfactorily to—previous ADHD therapies, including methylphenidate (MPH). Two further studies demonstrated the longer-term effectiveness of flexible-dose lisdexamfetamine in reducing ADHD symptoms, albeit maintenance of efficacy required ongoing treatment with the drug. Lisdexamfetamine was generally well tolerated in clinical trials, with an adverse event profile typical of that reported for other long-acting stimulants. Head-to-head comparisons with other long-acting agents, notably MPH and atomoxetine, are lacking. Nonetheless, on the basis of the available data, lisdexamfetamine provides a useful alternative option for the treatment of adults with ADHD, including those who have not responded adequately to previous ADHD therapies, including MPH.
KeywordsADHD Symptom Executive Functioning Atomoxetine Pittsburgh Sleep Quality Index Hippuric Acid
During the peer review process, the manufacturer of lisdexamfetamine was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
Compliance with Ethical Standards
The preparation of this review was not supported by any external funding.
Conflicts of interest
James Frampton is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.
- 3.National Institute for Health and Care Excellence. Attention deficit hyperactivity disorder: diagnosis and management of ADHD in children, young people and adults. NICE guidelines [CG72]. 2008. https://www.nice.org.uk/guidance/cg72. Accessed 7 Dec 2015.
- 4.All Wales Therapeutics and Toxicology Centre. AWMSG secretariat assessment report: Lisdexamfetamine dimesylate (Elvanse Adult®) 30 mg, 50 mg and 70 mg hard capsules. Reference number: 2534. 2015. http://www.awmsg.or. Accessed 14 Dec 2015.
- 13.Adler LA, Dirks B, Deas PF, et al. Lisdexamfetamine dimesylate in adults with attention-deficit/ hyperactivity disorder who report clinically significant impairment in executive function: results from a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2013;74(7):694–702.CrossRefPubMedGoogle Scholar
- 19.Shire. Elvanse 30 mg, 50 mg and 70 mg capsules, hard. UK summary of product characteristics 2015. https://www.medicines.org.uk. Accessed 24 Feb 2016.
- 20.Shire Pharmaceuticals Limited. Elvanse Adult 30 mg, 50 mg and 70 mg capsules, hard: UK summary of product characteristics. 2015. https://www.medicines.org.uk. Accessed 25 Feb 2016.
- 21.Shire Pharmaceutical Contracts Limited. Elvanse vuxen 30, 50, 70 mg kapslar,hårda. Swedish summary of product characteristics 2015. https://lakemedelsverket.se. Accessed 25 Feb 2016.
- 22.Shire Sweden AB. Elvanse (Lisdexamfetamin). Danish summary of product characteristics. 2015. http://pro.medicin.dk. Accessed 25 Feb 2016.
- 23.Shire US Inc. Vyvanse® (lisdexamfetamine dimesylate) capsules, for oral use. US prescribing information. 2015. http://pi.shirecontent.com. Accessed 25 Feb 2016.
- 25.Ermer J, Haffey MB, Richards C, et al. Double-blind, placebo-controlled, two-period, crossover trial to examine the pharmacokinetics of lisdexamfetamine dimesylate in healthy older adults. Neuropsychiatr. 2013;9:219–29.Google Scholar
- 30.Pennick M. Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine. Neuropsychiatr. 2010;6:317–27.Google Scholar
- 35.Wigal T, Brams M, Gasior M, et al. Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design. Behav Brain Funct. 2010;6:34.CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Fridman M, Hodgkins PS, Kahle JS, et al. Predicted effect size of lisdexamfetamine treatment of attention deficit/hyperactivity disorder (ADHD) in European adults: estimates based on indirect analysis using a systematic review and meta-regression analysis. Eur Psychiatry. 2015;30(4):521–7.CrossRefPubMedGoogle Scholar
- 38.US National Institutes of Health. ClinicalTrials.gov identifier NCT00697515. 2011. https://www.clinicaltrials.gov. Accessed 18 Nov 2015.
- 39.US National Institutes of Health. ClinicalTrials.gov identifier NCT00334880. 2009. https://www.clinicaltrials.gov. Accessed 18 Nov 2015.
- 40.US National Institutes of Health. ClinicalTrials.gov identifier NCT01101022. 2014. https://www.clinicaltrials.gov. Accessed 18 Nov 2015.
- 42.Babcock T, Dirks B, Adeyi B, et al. Efficacy of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder previously treated with amphetamines: analyses from a randomized, double-blind, multicenter, placebo-controlled titration study. BMC Pharmacol Toxicol. 2012;13:18.CrossRefPubMedPubMedCentralGoogle Scholar
- 45.Adler L, Wu J, Madhoo M, et al. Post hoc analyses of the efficacy of lisdexamfetamine dimesylate in adults previously treated with attention-deficit/hyperactivity disorder medication [poster]. In: 23rd European Congress of Psychiatry. 2015.Google Scholar
- 46.Adler LA, Dirks B, Deas P, et al. Self-Reported quality of life in adults with attention-deficit/hyperactivity disorder and executive function impairment treated with lisdexamfetamine dimesylate: a randomized, double-blind, multicenter, placebo-controlled, parallel-group study. BMC Psychiatry. 2013;13:253.CrossRefPubMedPubMedCentralGoogle Scholar
- 54.Lopez FA, Leroux JR. Long-acting stimulants for treatment of attention-deficit/hyperactivity disorder: a focus on extended-release formulations and the prodrug lisdexamfetamine dimesylate to address continuing clinical challenges. Atten Deficit Hyperact Disord. 2013;5(3):249–65.CrossRefGoogle Scholar
- 56.Goodman DW. Lisdexamfetamine dimesylate. The first prodrug stimulant. Psychiatry (Edgemont). 2007;4(8):39–45.Google Scholar
- 57.Medicines and Healthcare Products Regulatory Agency. Public assessment report decentralized procedure. Elvanse adult 30, 50 and 70 mg capsules, hard (lisdexamfetamine dimesylate). Procedure no.: UK/H/5567/001-03/DC. http://www.mhra.gov.uk. Accessed 15 Nov 2015.