Potential treatments for attention-deficit/hyperactivity disorder: a focus on Phase III trials

Stimulant medications, such as methylphenidate and amphetamine derivatives, and non-stimulant medications, such as atomoxetine, guanfacine, clonidine, and viloxazine, are considered the cornerstones of pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD). However, a significant number of individuals respond partially to these treatments or are concerned about side effects. This creates a need for new treatment strategies that target alternative neurobiological mechanisms and offer improved tolerability and efficacy profiles.

This review examines pharmacological agents currently in phase III clinical development or recently completed trials for the treatment of ADHD. We highlight four promising candidates: centanafadine, solriamfetol, CTx-1301, and NRCT-101SR. We discuss their pharmacological mechanisms, clinical efficacy, safety profiles, and regulatory status, with an emphasis on how these agents may address existing therapeutic gaps and the potential clinical implications. A literature search was conducted using PubMed and ClinicalTrials.gov databases for articles published between January 2018-July 2025.

Recent advances in ADHD pharmacotherapy suggest that approaches targeting monoaminergic systems beyond dopamine and noradrenaline reuptake inhibition may provide therapeutic benefits. Additionally, multi-phase extended-release formulations may improve adherence and enhance symptom control throughout the day. As phase III data become available, these agents have the potential to redefine ADHD treatment paradigms.