Current Investigational Drugs for the Treatment of Attention-Deficit/Hyperactivity Disorder

ABSTRACT

Introduction: Symptoms of attention-deficit/hyperactivity disorder (ADHD) were first described more than 100 years ago. It is a common neurobehavioral disorder that begins in childhood and often persists into adulthood. Treatment for ADHD has been available since Bradley first prescribed amphetamines for hyperkinetic boys more than 70 years ago. Although multiple effective medications for the treatment of ADHD are on the market, all have limitations. Stimulants are controlled substances and may not be effective or tolerable for all patients. The non-stimulants are not as effective as stimulants and have their own side effect profiles.

Areas Covered: In this review, the limitations of currently available medications including methylphenidates, amphetamines, atomoxetine, extended-release guanfacine and extended-release clonidine are considered and drugs in development for the treatment of ADHD are examined. Although the main focus is on phase I and II trials, drugs which may soon be marketed are also discussed.

Expert opinion: Multiple drugs are currently in development, with several targeting novel receptors originally identified using animal models. Since ADHD appears to be complex disorder associated with multiple genes, these models have often not predicted effectiveness in humans. Until there is a better understanding of the genetics of ADHD, drug development will remain challenging.

KEYWORDS:

• ADHD
• Attention-deficit/hyperactivity disorder
• stimulants
• nonstimulants

Article highlights

• Current pharmacological treatments for ADHD have significant limitations.

• Multiple stimulant and non-stimulant drugs are in development.

• Most stimulant formulations in the pipeline target patient convenience as several do not require swallowing intact capsules or tablets while others obviate the need to use a combination XR and IR compounds.

• The most novel stimulant formulations being studied are combined delayed- and extended-release drugs are designed to achieve early morning control upon awakening with continued efficacy throughout the day.

• Nonstimulants in development target unique receptors including GABA, glutamate, serotonin, and adenosine A_2A.This box summarizes key points contained in the article.

Acknowledgements

The authors thank J Schneider, an employee of the Center for Psychiatry and Behavioral Medicine, Inc for proofreading the manuscript.

Financial & competing interests disclosure

A Childress has acted as a consultant for Shire Pharmaceuticals Inc, Next Wave Pharmaceuticals, Sunovion, Ironsnhore, Rhodes, Neurovance, Neos and Arbor. She has also been a speaker for Shire Pharmaceuticals, Pfizer Inc and Arbor and is on the advisory boards of Pfizer Inc, Noven, NextWave Pharmaceuticals, Ironshore, Rhodes, Neurovance, Neos and Arbor. Furthermore, she has received research support from Shire Pharmaceuticals, Pfizer Inc, Noven, NextWave Pharmaceuticals, Lilly USA, LLC, Forest Research Institute, Otsuka, Sunovion, Ironshore, Rhodes, Theravance, Neurovance, Neos, Arbor, Tris, Purdue, Lundbeck and Alcobra. Finally, she has received writing support from Shire Pharmaceuticals Inc, Pfizer Inc, Ironshore, Rhodes and Neos. The authors have 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.