Stimulant medications or cerebral stimulants have been used in the treatment of ADHD for a very long time. Although the exact mechanism of action is not fully understood, several theories have been proposed. Stimulants are believed to inhibit the reuptake of dopamine and norepinephrine and thereby increase release of these transmitters from the neuron. Reuptake means that the neurotransmitters are taken back into the chemical system, and therefore they do not function properly. Stimulants allow these actions of reuptake to be stopped or slowed down to various degrees and channel the neurotransmitter to work. Individuals appear to react to stimulants in various ways. For this reason, failure of therapy with one agent does not mean the class is not effective and another agent within the class may work. If responses are ineffective, a stronger dose may be used, allowing for sufficient times between these doses. The word titration is used to refer to the different doses.

The most common stimulants are d-amphetamine and methyphenidate (MPH). d-Amphetamines have several trade names, the most common being Dexedrine; Ritalin is the trade name for MPH. Amphetamine was first used for the treatment of ADHD children in 1937; MPH has been used since the 1960s. A common drug pemoline (Cylert) was introduced in Europe a number of years before being approved in the United States. Pemoline was removed from the Canadian market in 1999 because of safety consideration; the U.S. FDA removed it from the market in 2005 because of liver toxicity.

Extensive experience with these medications is one of the advantages of using them; long-term information of their safety and efficacy is available. Currently there are 10 commonly used stimulant medications that are distinguished by their mode of delivery to the body. Medications can either be short- or long-acting; short-acting formulations are effective for 2 to 4 hours; long-acting formulations can last 8 to 12 hours. Also, long-acting formulations differ in how much drug is released into the body immediately compared to what is released over time. For example, one formulation may release 50 percent of the medication immediately, with the remaining 50 percent slowly entering the blood stream. Another formulation releases only 30 percent immediately with a slow release of the remaining 70 percent. The value of answering the questions about the time of difficulty can be seen here. Choosing the right medication often means finding the delivery system that works best for the individual.

Longer-acting formulations of both MPH and amphetamine have entered the market. One newdelivery systemis based on a ''bead'' technology, in which longand short-acting beads release the drug, mimicking twice-daily dosing and allowing for extended duration of effect. Another long-acting formulation uses an osmotic release oral system (OROS), in which an immediate release of part of MPH is contained in the capsule's overcoat, with the remainder of the drug osmotically released over the course of several hours. A formulation of mixed amphetamine salts (MAS) contains both d- and l-amphetamine isomers (forms of the drug) and is designed to give a double-pulsated delivery of amphetamines that prolongs its release. A new transdermal system delivers the drug in a discreet, clear patch that is applied once daily and releases a consistent amount of drug while the patch is worn and for about 3 hours after the patch is removed. Extended release formulations provide longer durations of action of 8 to 10 hours, resulting in the need for fewer daily administrations and eliminating the need to take medication while at school.

Adderall, approved in 1996 as a treatment of ADD/ADHD, is a cocktail or mixture of four drugs from the amphetamine family, which includes dextroamphetamine saccharate, amphetamine aspartate USP, and dextroamphetamine sulfate USP. Adderall is classified as a respiratory and cerebral stimulant. As a result, it has a broad spectrum of symptom coverage. It tends to last for about 6 hours per dose and can cover the entire school day. Some physicians say that it appears to be less harsh than Ritalin. However, concerns of the possibility of cardiovascular problems caused sales of Adderall XR to be suspended for 6 months in 2005. Similar concerns with Concerta related to psychiatric problems evoked further investigations by the FDA in July 2005, but the agency was not convinced there was enough evidence to declare a cause-effect relationship and decided more investigation was needed.

Researchers at the University of California, San Diego, researched a patch containing MPH, the ingredient found in Ritalin. The patch provides a steady level of drug through the skin to the blood stream and offers an alternative to twice-daily pills. The patch may reduce some of Ritalin's side effects, such as jitteriness and stomachaches because the effects are often due to fluctuations of MPH blood levels associated with taking the shortacting oral form of the drug several times a day.

Stimulants enhance the availability of dopamine, the neurotransmitter, to allow greater control over sustained attention.

Bibliography:

1) Faraone, S. V. et al. 2004. Attention-deficit/hyperactivity disorder in adults: A survey of current practice in psychiatry and primary care. Archives of Internal Medicine 164:1221-26.

2) Gibson, Aaron P. et al. 2006. Atmoxetine versus stimulants for treatment of attention deficit/hyperactivity disorder. Annals of Pharmacotherapy 40:1134-42.

3) Katusic, S. K. et al. 2005. Case definition in epidemiologic studies of ADHD. Annals of Epidemiology 15:430-37.

4) Oatis, M. D. ''Treatment-pharmacology.'' Discussion presented at the Attention Deficit Hyperactive Disorder (ADHD) AMA Media Briefing; September 9; New York, NY, 2004.

5) Swanson et al. 2007. Effects of stimulant medication on growth rates across 3 years in the MTA follow-up. Journal of American Academy of Child and Adolescent Psychiatry 46:1014-26.

6) Wender, Paul. 1987. The hyperactive child, adolescent, and adult: Attention deficit disorder through the lifespan. New York: Oxford University Press.

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