Adderall



Adderall is a pharmaceutical stimulant amphetamine used to treat attention-deficit disorder/attention-deficit hyperactivity disorder and narcolepsy. Severe cases of depression may also be treated with Adderall or other stimulants. It was first prescribed in the 1920s as an anorectic (under the brand name Obetrol), but such usage is now rare. Adderall is a schedule II controlled substance, meaning it has been deemed to have a high potential for abuse.

Use
Adderall was introduced in 1997 as instant-release tablets, which has since become available as the generic formulation "mixed amphetamine salts." The active ingredients of Adderall include a combination of dextroamphetamine and racemic amphetamine salts. Shire later introduced a gradual-release preparation of these ingredients, Adderall XR (e x tended  r elease), and retains patent rights on Adderall XR that will expire in 2009.

Chemistry
In particular, Adderall XR is composed of the following proportions of active ingredients:
 * 1/4 dextroamphetamine saccharate
 * 1/4 dextroamphetamine sulfate
 * 1/4 dextro/levo-amphetamine aspartate (racemic amphetamine)
 * 1/4 dextro/levo-amphetamine sulfate (racemic amphetamine)

The four component salts are claimed to be metabolized at different rates, thereby imparting a more gradual and "smoother" build-up and decline in effect compared to amphetamine preparations comprising only a single salt.

The average elimination half-life for dextroamphetamine is 10 hours in adults, and for levoamphetamine, 13 hours. Its effects are otherwise similar to other central nervous system stimulants of the same class and preparation (see amphetamine for details.).

The manufacturer claims that the mixture of salts makes Adderall's effects smoother, with softer highs and lows, than those of other treatments for the same disorders.

There is little evidence, however, to support this claim for immediate-release. A recent patent application for Adderall was a pharmaceutical composition patent listing a rapid immediate release oral dosage form. No claim of increased or smooth drug delivery was made. A recent double-blind, placebo-controlled crossover study, conducted among children, indicated that patients behaved similarly to other immediate release amphetamines. The authors found that sustained-release dexamphetamine (the main isomeric-amphetamine component of Adderall) had a longer duration of action, though dexamphetamine was less effective in the first few hours.

Dosing and Administration
Adderall is now sold in either an immediate-release tablet or an extended-release capsule, marketed as Adderall XR (for "eXtended Release"). Doses for both immediate-release and extended-release form come in 5, 10, 15, 20, 25, 30 and 100 mg tablets.

Adderall XR utilizes the Microtrol® delivery system to achieve the extended-release mechanism. This delivery system incorporates two beads: the first type of bead dissolves immediately and the second type releases four hours later. Maximum plasma concentration is achieved in seven hours, compared to regular Adderall IR (immediate-release) which reaches maximum plasma concentration within three hours. As a result of its high bioavailability, Adderall XR's effectiveness is not altered by food absorption in the gastrointestinal tract. However, tmax (mean plasma concentration) is prolonged by 2.5 hours (using a standard high-fat meal as the control). Medications that alter urinary pH will cause variations in amount and method of excretion and usage should be monitored when taken concurrently with Adderall.

Effects
Amphetamine, both as d-amphetamine (dextroamphetamine) and l-amphetamine (or a racemic mixture of the two isomers), is believed to exert its effects by binding to the monoamine transporters and increasing extracellular levels of the biogenic amines dopamine, norepinephrine and serotonin.

It is hypothesized that d-amphetamine acts primarily on the dopaminergic systems, while l-amphetamine is comparatively norepinephrinergic. The primary reinforcing and behavioral-stimulant effects of amphetamine, however, are linked to enhanced dopaminergic activity, primarily in the mesolimbic DA system. Amphetamine binds to the dopamine transporter (DAT) and blocks the transporters ability to clear DA from the synaptic space. In addition, amphetamine is transported into the cell which leads to dopamine efflux (DA is transported out of the cell and into the synaptic space via reverse transport of the DAT).

Double-blind, placebo-controlled studies of dextroamphetamine in normal subjects have shown significant performance increases on cognitive tasks and decreased reaction time.

Amphetamines have been shown to pass through into breast milk. Because of this, mothers taking medications containing amphetamines are advised to avoid nursing during their course of treatment.

Side effects
Aggression, new abnormal thoughts/behaviors, mania, growth suppression, worsening of motion or verbal tics and Tourette’s syndrome have been associated with use of drugs of this type.

Side effects in children

 * decreased appetite
 * difficulty falling asleep
 * stomachache
 * emotional lability

Side effects in adolescents

 * loss of appetite
 * difficulty falling asleep
 * headache
 * stomachache
 * weight loss

Side effects in adults

 * dry mouth
 * loss of appetite
 * difficulty falling asleep
 * headache
 * weight loss

Rare side effects
These symptoms require immediate medical assistance:
 * symptoms of tourettism
 * aggression
 * symptoms of depression
 * seizures or abnormal EEGs
 * high blood pressure
 * swelling of feet/ankles

Dependence and addiction caused by abusing Adderall
Tolerance, psychological dependence, and social disability can occur when amphetamines are abused. The manufacturer warns against exceeding the prescribed dosage, injecting the drug, or insufflation of the drug.

Contraindications
Serotonin syndrome is a rare but potentially fatal condition which occurs when an amphetamine such as Adderall is used within 1-2 weeks of taking a monoamine oxidase inhibitor (MAOI).

Performance-enhancing use
Because Adderall uses amphetamine stimulants to help the user concentrate for extended periods of time, many students today request Adderall from doctors in order to use it as a study aid. Thus, it is increasingly popular on college campuses. The largest benefit to students is Adderall's ability to give students the power to learn and study what would usually be uninteresting material. Thus it is used extensively by students wishing to pull all-nighters to study for tests. Because of the appetite-suppressing properties of amphetamines, it is also sought after by those wishing to lose weight. Another less common use for students is to take Adderall before or during a night of heavy drinking in order to remain alert and active despite being intoxicated.

Research done by the National Institute of Drug Abuse (NIDA) shows the more competitive the college, the higher the incidence of stimulant use. An article published stated the findings of a nationwide survey of thousands of college students. The findings of this past April 2006 survey shows 5.9% use rates among the more competitive campuses, compared to 1.3% use rates among less competitive campuses. Breaking down the use pattern even further, this same sample done by NIDA reveals whites were more likely to use stimulants compared to African Americans and Asians, at rates of 4.9%, 1.6%, and 1.3% respectively. Further, students with lower grade point averages of B’s or below use stimulants at a rate of 5.2%, compared to students earning B+ or above who use this medication at rates of only 3.3%. This research also specifically identified that students involved in sororities or fraternities use stimulants at a much higher rate of 8.6% compared to nonmembers who reported use at rates of only 3.3%.

Another major concern about the use of Adderall among college students is the psychological dependence that may cause students to lose faith in their own ability to perform well and the dependence on the advantageous effects of stimulant medication. Jackie Kurta, an Alcohol and Drug Specialist at UC Santa Barbara’s Student Heath Services states, “Students start out taking study drugs one time to study. The drugs work so well that the students begin to lose confidence in their own abilities to study without them,” (Hirschey).

Aside from being used by college students as a study aid, Adderall has been used as an off label drug for weight loss. Adderall’s side effect of weight loss and appetite suppression is a desired result for those trying to lose weight. It is administered as part of a “cocktail” of other off label prescription drugs that have side effects used to treat obesity. There have not been any scientific studies performed to evaluate the effectiveness of this form of treatment and is viewed as a very risky and potentially dangerous way to shed pounds.

Government warnings
On February 9, 2005, Health Canada suspended all sales of Adderall XR after data collected by manufacturer Shire Pharmaceuticals linked the drug to 12 sudden deaths in American children between the years of 1999 to 2003. Further research, however, found little data suggesting use of Adderall resulted in an increased risk of cardiac defect. Of the twelve sudden deaths positively linked to pediatric Adderall users during the four year period, five had known pre-existing cardiac conditions, one died after strenuous exercise in 110 degree heat and two had levels suggestive of an overdose. Given the more than 37,000,000 prescriptions for Adderall filled during the four years, the US Food and Drug Administration could find no increased risk of sudden death among Adderall users beyond the normal rate of the general population. In August, 2005, Health Canada followed the committee report of three independent physicians and lifted the ban on Adderall XR. Given that persons with ADHD are more likely to engage in risky or dangerous behavior, it has been suggested that stimulant medications for persons with ADHD may actually result in lower incidence of premature death. The use of Adderall is generally not advised in those persons with pre-existing cardiac or mental illnesses. It is also not advised in persons who have a history of drug abuse. Although FDA safety advisors voted 8 to 7 to issue a Black Box Warning, the FDA's pediatric advisory committee refused to give the drug its most severe black box warning in March, 2006. A Black Box Warning regarding amphetamine abuse potential is in place, however.

Manufacturers
Adderall is manufactured by Shire Pharmaceuticals and is distributed by Catalytica Pharmaceuticals Inc. of Greenville, North Carolina. Generic equivalents (known to pharmacists as "amphetamine salts," "mixed amphetamines," or simply "amphetamines," among other things) are also distributed in the United States by Barr Pharmaceuticals, Mallinckrodt Pharmaceuticals, Eon Labs and Ranbaxy Laboratories.

Notes and references
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