New Drug Treatments for ADHD

Several new treatments for attention-deficit/hyperactivity disorder have been developed in recent years. For the most part, new commercial products during this time have been reformulations of existing molecules differentiated by delivery systems, with the intent of extending the duration of effect, reducing the abuse liability, or otherwise adding features of potential clinical benefit.

New stimulant packaging has been introduced with highly novel methods of delivery affecting their onset and duration. New nonstimulant preparations have evaluated the effects of alpha-2 adrenoceptor agonists as monotherapy and as treatments combined with stimulants.

In this clinically oriented review, we focus on medications that have been introduced in the past 5 years and on investigational agents not yet marketed for ADHD.

Historical Context

After many years during which the major treatments were immediate-release (IR) racemic methylphenidate hydrochloride (d, l-MPH HCl); dextroamphetamine (d-AMP); mixed amphetamine salts; and first-generation time-release products (eg, Dexadrine Spansules, Ritalin SR), an oral osmotically delivered (OROS) form of MPH HCl (Concerta) was approved in 2000.¹ The OROS system provided a consistent delivery of MPH by means of osmotic pressure at a controlled rate throughout a 12-hour duration of effect. By design, it increased the rate of release so that more drug was delivered later in the day.

From 2001-2002, there was FDA approval of two forms of biphasically released methylphenidate (Ritalin LA, which delivers equal amounts of IR and delayed-release MPH; and Metadate CD, which delivers 30% IR and 70% delayed-release MPH to achieve higher pharmacokinetics later in the day). An extended-release version of mixed AMP salts (Adderall XR); a selective norepinephrine reuptake inhibitor, atomoxetine (Strattera); and a formulation of the d-threo enantiometer of MPH HCl (Focalin) were also approved. In 2005, Focalin extended release (XR) was introduced, which, similar to Ritalin LA, uses a beaded system with 50% IR and 50% delayed delivery.

New Long-Acting Stimulant Products

Lisdexamfetamine (LDX) was approved by the FDA for treating ADHD in children in 2007 and was approved for use in adults in 2008.² Unique among attention-deficit/hyperactivity disorder (ADHD) treatments, LDX is a prodrug. A prodrug is defined as an inactive compound that depends on in vivo processes to convert the product into active medication. LDX consists of an l-lysine molecule that is bonded to a d-amphetamine...