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

Abstract

Introduction: 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.

Area covered: 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.

Expert opinion: 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.