Adderall detailed information



Adderall  is a pharmaceutical psychostimulant comprising mixed amphetamine salts. The drug is used primarily to treat attention-deficit/hyperactivity disorder and narcolepsy. Adderall has also been used successfully to manage severe cases of treatment-resistant depression. It is a Schedule II controlled substance, meaning that it has been deemed to have a high potential for abuse and addiction despite genuine medical uses.

Use
Brand-name Adderall was introduced in 1996 in the form of a multi-dose, instant-release, tablet derived from the original formula used in the weight management drug Obetrol. It has since become available in a generic formulation of "mixed amphetamine salts." The active ingredients of Adderall include a combination of dextroamphetamine and racemic d/l-amphetamine salts. Shire Pharmaceuticals later introduced an extended-release preparation of these ingredients in a variety of dosages, under the brand name "Adderall XR" (e x tended  r elease), on which Shire still retains exclusive patent rights until 2019.

Chemistry
Specifically, Adderall XR is composed of the following proportions of active ingredients:


 * 1/4 dextroamphetamine saccharate
 * 1/4 dextroamphetamine sulfate
 * 1/4 aspartate (racemic d/l-amphetamine)
 * 1/4 sulfate  (racemic d/l-amphetamine)

These four salts are metabolized at different rates and possess diverse half lives, therefore resulting in a less dramatic onset and termination of therapeutic action; as compared to single salt amphetamine preparations.

The average elimination half-life in adults for dextroamphetamine is 10 hours and 13 hours for l-amphetamine. Breakdown rates are affected by urinary and stomach pH, weight, gender, other medications, and age in the direction of +/- roughly 2 hours. Its effects are similar to other CNS stimulants of the same class and preparation (see amphetamine for details.).

Urinary and stomach pH levels can significantly affect (d,l)-amphetamine excretion and absorption. Co-administration of acidic substances (eg; citric acid) causes an accelerated excretion of (d,)-amphetamine while co-administration of alkaline agents (eg; antacids) causes a marked increase in both retention and absorption of amphetamines sometimes resulting in dangerously high amphetamine levels.

Dosing and administration
Adderall is marketed as either an immediate-release tablet, Adderall, or an extended-release capsule, Adderall XR ("eXtended Release"). Doses for both forms come in 5, 10, 12.5, 15, 20, 25, and 30mg strengths.

Adderall XR utilizes the Microtrol® extended-release delivery system. This system incorporates two types of beads: the first dissolves immediately, releasing half of the medication, while the second type dissolves much more slowly releasing the remaining medication four hours later. Maximum plasma concentration is achieved in seven hours, compared to regular Adderall, 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, 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.

Manufacturer's claims of instant release have been disputed. A 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 dextro-amphetamine was less effective in the first few hours.

Mechanism of Action
Amphetamine, both as dextroamphetamine and levoamphetamine (or a racemic mixture of the two enantiomers), 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).

Amphetamine also possesses the ability to inhibit the enzymes MAO-A and MAO-B, or "Monoamine Oxidase A and B" in high doses. MAO-A is responsible for the break down of serotonin, dopamine, norepinephrine and epinephrine. MAO-B is responsible for breaking down dopamine (more potently than MAO-A) and phenylethylamine, or "PEA". Phenylethylamine has actions similar to amphetamine itself and is thought to be involved in feelings of lust, confidence, obsession and sexuality. Some of the first antidepressants successfully marketed are in fact Monoamine Oxidase inhibitors. However, MAO inhibition seen with amphetamine is neither substantial enough in duration and quantity to entail the need for a tyramine limited diet, unlike the more potent and long lived MAO inhibiting antidepressants.

Amphetamine's ability to cause the inhibition of MAO results in the accumulation of monoamines while amphetamine also directly stimulates the release of these neurochemicals, resulting in a potent elevation in monoamine neurotransmission.

Double-blind, placebo-controlled studies of dextroamphetamine in prepubertal 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 breastfeeding 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

Side effects in overdose
These symptoms require immediate medical assistance:
 * symptoms of tourettism
 * aggression
 * symptoms of depression
 * seizures or abnormal EEGs
 * high blood pressure
 * tachycardia
 * swelling of hands/feet/ankles (notice for example finger tips getting numb)
 * delusions
 * sweating
 * vomiting
 * Dehydration
 * Unexplained muscle pain

Adderall abuse
Tolerance, extreme psychological dependence, and severe social disability can occur when amphetamines are abused. The manufacturer warns against exceeding the prescribed dosage, injecting the drug, or insufflation of the drug. Prolonged high doses of amphetamines followed by an abrupt cessation can result in extreme fatigue and mental depression. Chronic abuse of amphetamines can manifest itself as psychosis, often indistinguishable from schizophrenia.

Contraindications, interactions, and precautions
The following provides only general guidelines and is not comprehensive. Please refer to a more comprehensive list for further information regarding co-administration of amphetamine with other substances.


 * SSRIs (selective serotonin reuptake inhibitors) — While rare, the possibility for serotonin syndrome exists with this combination. Use only when it is directed. eg; Fluoxetine, Citalopram, Paroxetine, etc.
 * NRIs (norepinephrine reuptake inhibitors) — NRI medications and amphetamine both enhance noradrengic activity. Possible augmentation/potentiation of effects. Use only when directed. eg; Atomoxetine (Strattera)
 * SNRIs (selective serotonin-norepinephrine reuptake inhibitors) — See SSRIs and NRIs.
 * Bupropion — Both bupropion and amphetamine have noradrengic and dopaminergic activity. Possible augmentation/potentiation of effects. Bupropion has pro-convulsant properties that may be enhanced or cumulatively potentiated by amphetamine.(eg; bupropion (Wellbutrin IR, SR, XL) and (Zyban) etc.) Use only when directed.
 * MAOIs (monoamine oxidase inhibitors) — Do not administer amphetamine's for a minimum of 2 weeks after last use of MAOI type drug. Possible hypertensive crises, dangerously elevated amphetamine levels. (eg; Phenelzine (Nardil), Selegiline (Emsam), Iproniazid (Iprozid) etc.) There are preliminary trials of low dose amphetamine and MAOIs being administered together; however, this is to only be done under strict supervision of the prescribing parties.
 * Tricyclics (tricyclic antidepressants) — See SNRIs and SSRIs. Possible potentiation of 5htp (serotonin), dopamine and norepinephrine related drug effects. Use only when indicated. (eg; Imipramine (Tofranil, Janamine) etc.)

Performance-enhancing use
Adderall is a stimulant which taken at the right dose helps with concentration. Research done by the National Institute of Drug Abuse (NIDA) shows the more competitive the college, the higher the incidence of stimulant use. The abuse of Adderall among college students may lead to a psychological dependence that may cause students to lose faith in their own ability to perform well and the dependence on the drug.

Adderall has also 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. 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 U.S. 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.