Beyond stimulants: a systematic review of randomized controlled trials assessing novel compounds for ADHD

Beyond stimulants: a systematic review of randomized controlled trials assessing novel compounds for ADHD

Nageye F, Cortese S.


Expert Rev Neurother. 2019 Jun 5.

doi: 10.1080/14737175.2019.1628640.


Commentary* by Dr. Margaret Weiss: The pipeline for medication treatment of ADHD includes novel compounds. Real life effectiveness may mean that this will allow us to treat some patients who were otherwise non-responsive.




Despite stimulants being highly efficacious in short-term randomized controlled trials (RCTs), not all patients respond or can successfully tolerate them. A number of novel non-stimulant options are currently in the pipeline for the treatment of ADHD.


Areas covered

The authors conducted a systematic review of RCTs registered in in the past five years (January 2014 and February 2019), supplemented by searches in PubMed, Web of Science, and drug manufacturers websites to find recent RCTs on novel non-stimulant ADHD medications.


Expert opinion

 The authors found 28 pertinent RCTs of compounds acting on a variety of biological targets, including Dasotraline, Viloxazine (SPN-812), Centanafadine SR (CTN SR), OPC-64005, Fasoracetam (NFC-1, AEVI-001), Metadoxine (MDX), Vortioxetine, Tipepidine Hibenzate, Oxytocin, Sativex (delta-9-tetrahydrocannabinol (THC) plus cannabidiol), Mazindol, and Molindone hydrochloride (SPN-810). Given the high effect size found in RCTs of stimulants in terms of efficacy on ADHD core symptoms, it is unlikely that these novel agents will show better efficacy than stimulants, at the group level. However, they may offer comparable or better tolerability. Additionally, agents acting on etiopathophysiological targets disrupted in specific subgroups of patients with ADHD will move forward the pharmacotherapy of ADHD from a “one size fits all” to a “precision medicine” approach.


* Abstracts are selected for their clinical relevance by Dr. Margaret Weiss, Director of Clinical Research, Child Psychiatry, Cambridge Health Alliance, Harvard University. Her commentary reflects her own opinion, is not approved, or necessarily representative, of the opinion of the CADDRA board.


The website is hand-crafted in ZippyHippo online marketing studio.