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

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.

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.

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.