Emerging drugs for the treatment of attention-deficit hyperactivity disorder (ADHD)

Abstract

Introduction: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting up to 5.3% of children and 2.5% of adults depending on the country considered. Current pharmacological treatments for ADHD are based on stimulant or non-stimulant medications, targeting dopaminergic and noradrenergic systems in the frontal cortex and dopaminergic system in the basal ganglia. These drugs are effective and safe for the majority of patients, whereas about 20% of treated patients do not tolerate current therapies or experience insufficient efficacy. The adequate treatment of ADHD is necessary to allow a proper social placement and prevent the acquisition of additional, more severe, comorbidities. Areas covered: We conducted a review of the scientific literature and of unpublished/ongoing clinical trials to summarize the advances made in the last 10 years (2010-2020) for the pharmacological treatment of ADHD. We found many pharmacological mechanisms beyond dopaminergic and noradrenergic ones have been investigated in patients. Expert opinion: Some emerging drugs for ADHD may be promising as add-on treatment especially in children, amantadine to enhance cognitive functions and tipepidine for hyperactivity/impulsivity. Stand-alone emerging treatments for ADHD include viloxazine and dasotraline, which will soon have more clinical data available to support market access requests.

Treatment of ADHD: Drugs, psychological therapies, devices, complementary and alternative methods as well as the trends in clinical trials

“…Additionally, there are several promising drug candidates (PDC-142, centanafadine, tipepidine) that are under research and development and have been used as trial interventions during the last 3 years period. Moreover, the emergence of new drug formulations (ADAIR), presence of promising targets (HRH3), and desire to overcome such issues as short-term effectiveness, low adherence, and non-tolerability ( Pozzi et al, 2020 ) also contributes to the development of the field.…”

“…In addition, modafinil–stimulant, initially approved by the FDA as a wakefulness-promoting agent failed to become a treatment option for ADHD patients due to safety concerns ( Heal et al, 2013 ). For some medications, no results were published (e.g., CX717) ( Pozzi et al, 2020 ). Thus, only 10 unique agents are currently active, and the most promising class in this group is represented by antidepressants accounting for four agents.…”

“…Tipepidine is a small-molecule non-narcotic antitussive drug that has been used in children in Japan since 1959. It is assumed that the pharmacological effect of tipepidine on ADHD symptoms is due to the inhibition of G protein-coupled inwardly rectifying potassium (GIRK)-channel currents with the subsequent regulation and balancing of monoamines level in the brain ( Hashimoto and Sasaki, 2015 ) Tipepidine showed some promising results, regarding improvement of ADHD symptoms in several phase 2 clinical trials, however, more trials with the big sample are needed to validate the therapeutic benefits of this agent ( Pozzi et al, 2020 ). At the moment, no subsequent studies have been initiated since.…”

“…The number of unique entities in other groups ranges from two to six agents per class.Surprisingly, we can notice that the overwhelming majority of agents are discontinued, 31 out of 44 agents in total for all of the classes taken for analysis. The main reason for drug discontinuation was lack of efficacy or safety (e.g., bradanicline, vortioxetine, bavisant, PF-03654746, NS-2359, AZD1446)(Learned et al, 2012;Haig et al, 2014;Pozzi et al, 2020). It is worth noting, that all of these agents did not succeed in phase 2 clinical trials.…”

Autism and ADHD in the Era of Big Data; An Overview of Digital Resources for Patient, Genetic and Clinical Trials Information

“…While these medications are safe and effective for the majority of patients, a considerable proportion of patients have inadequate responses, poor tolerance, contraindication or experience side effects. These issues, in addition to long-term effectiveness, are the focus of nearly all drugs in development for ADHD [ 27 , 28 ]. For both disorders, non-pharmacological interventions, such as behavioral-based therapies and social skills training, are usually recommended, and in some cases are regarded as a standard addition to drug treatment.…”