CNS Drugs

, Volume 26, Issue 3, pp 245–268 | Cite as

The Pharmacology and Clinical Outcomes of Amphetamines to Treat ADHD

Does Composition Matter?
  • Paul Hodgkins
  • Monica Shaw
  • Suzanne McCarthy
  • Floyd R. SalleeEmail author
Review Article


Attention-deficit hyperactivity disorder (ADHD) treatment options include pharmacological and nonpharmacological approaches. In North America, psychostimulants (amphetamine and methylphenidate) are considered first-line pharmacological treatments for patients (children, adolescents and adults) with ADHD. However, in the UK, National Institute for Health and Clinical Excellence (NICE) guidelines have placed short-acting d-amphetamine as a third-line treatment option due to a lack of contemporary, published clinical trials on its efficacy and the concerns from clinical and patient experts regarding the potential for increased abuse and/or misuse compared with methylphenidate. These guidelines do not account for some of the more recent amphetamine products that have been developed to alleviate some of these concerns, but that are not currently approved in the UK or other European countries. The purpose of this review is to describe the pharmacology and clinical efficacy of various amphetamine compositions, as well as to explore the apparent differences in these compositions and their associated risks and benefits. A PubMed literature search was conducted to investigate amphetamine pharmacology, clinical efficacy and safety and ADHD outcomes in the published literature from 1980 through March 2011. Search terms included the keywords ‘ADHD’ or ‘ADD’ or ‘hyperkinetic disorder’ and any of the following keywords combined with ‘or’: ‘amphetamine’, ‘dexamphetamine’, ‘mixed amphetamine salts’, ‘lisdexamfetamine’ and ‘methamphetamine’. The search included English-language primary research articles and review articles but excluded editorial articles and commentaries. The literature search resulted in 330 articles. Pertinent articles relating to amphetamine pharmacology, compositions, clinical efficacy and safety, effectiveness and tolerability, ADHD outcomes and abuse liability were included in this review. The different delivery profiles of amphetamine compositions result in pharmacological and pharmacokinetic differences that contribute to varying effects in the clinical treatment of ADHD, ADHD outcomes and abuse liability. The efficacy and safety of amphetamine compositions for the treatment of ADHD have been demonstrated in clinical trials and meta-analyses, and the long-acting amphetamine compositions have been widely studied and found efficacious without increased adverse effects. Long-acting amphetamine compositions offer the obvious advantage of enhanced duration of action over short-acting amphetamine compositions, and lisdexamfetamine has been shown to have reduced abuse liability compared with short-acting amphetamine.


Amphetamine Atomoxetine Medication Possession Ratio Abuse Liability Lisdexamfetamine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Financial support for manuscript development was provided by Shire Development, Inc. Paul Hodgkins is an employee of Shire Pharmaceuticals Inc. Monica Shaw is an employee of Shire Pharmaceuticals. Suzanne McCarthy has received research support from Shire Development, Inc. Floyd R. Sallee is a consultant for Shire PLC, Otsuka Research and Development, Shionogi Pharma, Sunovion, Nextwave Pharma and AstraZeneca. Dr Sallee is a shareholder and member of the board of directors of P2D, Inc. The authors acknowledge that, under specific direction from the authors, editorial assistance in the form of first draft preparation and subsequent revisions of this manuscript was provided by Laura Miesle, PharmD, CMPP, of The JB Ashtin Group, Inc.


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© Adis Data Information BV 2012

Authors and Affiliations

  • Paul Hodgkins
    • 1
  • Monica Shaw
    • 2
  • Suzanne McCarthy
    • 3
  • Floyd R. Sallee
    • 4
    Email author
  1. 1.Shire PharmaceuticalsWayneUSA
  2. 2.Shire PharmaceuticalsBasingstokeUK
  3. 3.School of PharmacyUniversity College CorkCorkIreland
  4. 4.Department of Psychiatry and Behavioral NeuroscienceUniversity of Cincinnati Academic Health CenterCincinnatiUSA

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