New Drugs to Treat ADHD: Opportunities and Challenges in Research and Development

David J. Heal, Jane Gosden, Sharon L. Smith

Research output: Chapter or section in a book/report/conference proceedingChapter or section

4 Citations (SciVal)


Since the landmark MTA (Multimodal Treatment of ADHD) trial unequivocally demonstrated the efficacy of methylphenidate, catecholaminergic drugs, especially stimulants, have been the therapeutic mainstay in treatment of Attention-Deficit Hyperactivity Disorder (ADHD). We review the new drugs which have entered the ADHD formulary. The lessons learned from drug-candidates that have succeeded in clinical trials together with those that have not have also been considered. What emerges confirms and consolidates the hypothesis that clinically effective ADHD drugs indirectly or directly increase catecholaminergic neurotransmission in the prefrontal cortex (PFC). Attempts to enhance catecholaminergic signalling through modulatory neurotransmitter systems or cognitive-enhancing drugs have all failed. New drugs approved for ADHD are catecholaminergic reuptake inhibitors and releasing agents, or selective noradrenaline reuptake inhibitors. Triple reuptake inhibitors with preferential effects on dopamine have not been successful. The substantial number of failures probably accounts for a continued focus on developing novel catecholaminergic and noradrenergic drugs, and a dearth of drug-candidates with novel mechanisms entering clinical development. However, substantial improvements in ADHD pharmacotherapy have been achieved by the almost exclusive use of once-daily medications and prodrugs, e.g. lisdexamfetamine and Azstarys®, which improve compliance, deliver greater efficacy and reduce risks for diversion and abuse.

Original languageEnglish
Title of host publicationCurrent Topics in Behavioral Neurosciences
EditorsS. C. Stanford, E. Sciberras
Place of PublicationCham, Switzerland
PublisherSpringer Science and Business Media Deutschland GmbH
Number of pages48
ISBN (Electronic)9783031118029
ISBN (Print)9783031118012
Publication statusE-pub ahead of print - 30 Apr 2022
Externally publishedYes

Publication series

NameCurrent Topics in Behavioral Neurosciences
ISSN (Print)1866-3370
ISSN (Electronic)1866-3389


  • ADHD drugs
  • Attention-deficit hyperactivity disorder
  • Treatments

ASJC Scopus subject areas

  • Behavioral Neuroscience


Dive into the research topics of 'New Drugs to Treat ADHD: Opportunities and Challenges in Research and Development'. Together they form a unique fingerprint.

Cite this