Recent advances in pharmacological management of attention-deficit/hyperactivity disorder: moving beyond stimulants

ABSTRACT

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder characterized by impairing inattention and/or hyperactivity and impulsivity in children and adults. Although medications have been available to treat ADHD symptoms for decades, many are stimulant formulations. Stimulants, such as amphetamine and methylphenidate, are available in more than two dozen formulations, but all have similar adverse effects and carry a risk of misuse and dependence.

Areas covered

In the United States (US), several nonstimulants are available to treat ADHD. Two, including atomoxetine and viloxazine extended-release (ER), are approved by the Food and Drug Administration for the treatment of ADHD in children and adults. Two others, clonidine ER and guanfacine ER, are only approved for children and adolescents in the US. Several other compounds are under investigation. Drugs in Phase 3 trials include centanafadine, solriamfetol, and L-threonic acid magnesium salt. Efficacy and safety data for nonstimulants is presented.

Expert opinion

Although many effective formulations for the treatment of ADHD are available, more than 33% of children and 50% of adults discontinue treatment during the first year. The lack of individual drug response and tolerability are reasons many stop treatment. The development of new nonstimulants may offer hope for patients who need medication alternatives.

KEYWORDS:

• ADHD
• attention-deficit/hyperactivity disorder
• nonstimulant
• atomoxetine
• viloxazine
• clonidine
• guanfacine
• centanafadine

Article highlights

• In the United States (US) all Food and Drug Administration (FDA) approved medications, including stimulants and nonstimulants, can be used as first-line treatments, while the National Institute for Health and Care Excellence (NICE) guidelines recommend stimulants as first-line for children and adults.

• Atomoxetine and viloxazine extended-release (ER) are norepinephrine reuptake inhibitors approved to treat ADHD in children and adults in the US.

• Clonidine ER and guanfacine ER are norepinephrine α2A-adrenergic receptor (α_2A-AR) agonists.

• The efficacy and side effect profiles for nonstimulants differ from stimulants.

• Despite the availability of multiple medications for the treatment of ADHD, more than 50% of adults discontinue treatment within 12 months of initiation, often due to tolerability or lack of effect.

• To fill unmet patient needs, three drugs are in late-stage development for the treatment of ADHD and include centanafadine, solraimfetol, and l-threonic acid magnesium salt.

Declaration of interest

A Childress has received research support, served on an advisory board, has been a consultant or speaker, or has received writing support from the following: Aardvark, Acadia, Adlon, Akili, Allergan, Attentive, Axial, Axsome, Cingulate, Corium, Emalex, Ironshore, Kempharm, Lumos, Neurocentria, Noven, Otsuka, Purdue, Receptor Life Sciences, Sunovion, Supernus, Takeda, Tris, and Tulex during the past 3 years.

The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.