Adderall
Encyclopedia
Adderall is a brand name of amphetamine
salts–based medication used for attention-deficit hyperactivity disorder
and narcolepsy
. It is a brand-name psychostimulant medication composed of racemic
amphetamine
aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine
saccharide, and dextroamphetamine sulfate, which are all amphetamine salts. It is thought to work by increasing the amount of dopamine
and norepinephrine
in the brain. In addition, the drug also acts as a potent dopamine reuptake inhibitor
and norepinephrine reuptake inhibitor
. It is available in two formulations: IR (Instant Release) and XR (Extended Release). The immediate release formulation is indicated
for use in Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy
, while the XR formulation is approved for use only with ADHD.
Like other stimulant prescription drugs, Adderall directly affects the mesolimbic reward pathway in the brain. Amphetamine salts preparations are considered to have high abuse potential, and it is classified as Schedule II by the US DEA
.
and narcolepsy
. It has been used to treat obesity, but The American Society of Health-System Pharmacists does not recommend this use.
(ADHD), and in many patients it presents minimal side-effects. Depending on dosage, the beneficial effects of stimulant medications can last several hours, allowing improved performance throughout the day. Compared to the similar medication methylphenidate
(sold under the brand name Ritalin and others), studies have suggested that Adderall is slightly more potent and has a longer period of efficacy, especially at lower doses. For those who experience adverse side-effects to Ritalin or for whom Ritalin has become ineffective, Adderall is often recommended as a substitute.
For adolescents and adults, there is not adequate evidence that doses greater than 20 mg/day confer additional benefit,
although higher doses may be necessary due to variations in body weight.
obesity
.
Adderall XR utilizes the Microtrol
extended-release delivery system, incorporating 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 instant-release 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 900-calorie standard high-fat meal as the control). Medications that alter urinary pH will cause variations in the 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 US patent granted 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 35 children ages 5–12 indicated that patients behaved similarly to those having taken other immediate-release amphetamines. The authors found that sustained-release dexamphetamine (the main isomeric-amphetamine component of Adderall) had a longer duration of action, however -amphetamine was less effective in the first few hours.
Studies of long-term use of Adderall and methylphenidate in children have shown a temporary decrease in growth rate that does not affect final adult height. Stimulant medications also decrease appetite in some people, leading to weight loss, and this effect is more common with methylphenidate than Adderall methylphenidate or atomoxetine. Changes in vision have been reported with both Adderall and methylphenidate.
Women who are pregnant should avoid taking Adderall, especially during early pregnancy. Studies on rats show long-term neurological and behavioral changes resulting from prenatal and early postnatal exposure to amphetamines.
suspended all sales of Adderall XR after data collected by manufacturer Shire Pharmaceuticals linked the drug to 12 sudden deaths in American children. Further research found data suggesting use of Adderall resulted in an increased risk of cardiac defect. Although more than 37 million prescriptions for Adderall were filled during the four years prior, the U.S. Food and Drug Administration
could find no increased risk of sudden death among Adderall users.
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. In September 2008, Britain's National Institute for Health and Clinical Excellence urged physicians not to prescribe Adderall or similar drugs to children under 5, and to exhaustively consider other approaches to behavioral modification before prescribing such drugs to children 5 and up.
, irritability, and mental depression. Chronic abuse of amphetamines can result in the manifestation of amphetamine psychosis
.
stimulants of the same class and preparation. (See amphetamine for details.)
Urinary and stomach pH levels can have a strong effect on -amphetamine excretion and absorption. An acidic stomach and GI pH will decrease the absorption of Adderall, and acidic urine levels will decrease the reabsorption of the drug through the renal system. Co-administration of acidic substances (e.g., citric acid
) causes decreased renal reabsorption of -amphetamine; whereas, alkaline agents (e.g., antacids) may cause a marked increase in renal tubular reabsorption. The increased reabsorption can increase the retention of amphetamines, with potential to result in dangerously high serum
levels.
compounds in equal proportions: dextroamphetamine
saccharate, dextroamphetamine
sulfate, racemic amphetamine
aspartate monohydrate, and racemic amphetamine
sulfate. Breakdown rates are affected by many factors including urinary and stomach
pH
, weight, gender, other medications being taken, and age. Alkalinity increases bioavailability, while acidity causes the drug to be excreted more quickly. Manufacturers claim that the mixture of salts in Adderall XR makes its effects smoother (that is, makes softer highs and lows). The mixture of salts and their ratios are as follows:
These four salts are metabolized
at different rates and possess diverse half lives
, thereby resulting in a less dramatic onset and termination of therapeutic action, as compared to single-salt amphetamine preparations.
elimination half-life
for d-amphetamine
is 10 hours in adults; 11 hours in adolescents aged 13–17 years and weighing less than or equal to 75 kg/165 lbs; and 9 hours in children aged 6 to 12 years. For the l-amphetamine
, the mean elimination half-life in adults is 13 hours; 13 to 14 hours in adolescents; and 11 hours in children aged 6 to 12 years. On a mg/kg body weight basis children have a higher clearance than adolescents or adults."
The generic version of Adderall IR is available as generic drugs but the generic version of Adderall XR is only available as authorized generics
. Authorized generics are still manufactured by the brand name manufacturer but marketed and sold by a different company. Authorized generics are exactly the same as the brand name product both in active and inactive ingredients—they go through exactly the same brand manufacturing line, yet different labels are put on at the end of the manufacturing process.
With respect to central stimulant actions, the S(+) isomer (i.e., dextroamphetamine) is several times more potent than its R(-)enantiomer (i.e., levoamphetamine); this is not necessarily the case with other actions produced by amphetamine, in particular those produced in the periphery such as its cardiovascular actions. Dextroamphetamine induces more euphoria, whereas levoamphetamine induces more depression. The overall greater potency of the dextro form to central actions suggests that this form may have a higher potential for abuse.
Adderall’s inclusion of levoamphetamine provides the pharmaceutical with a quicker onset and longer clinical effect compared to pharmaceuticals formulated exclusively of dextroamphetamine.
Although it seems the human brain has a preference for dextroamphetamine over levoamphetamine, it has been reported that certain children have a better clinical response to levoamphetamine. Amphetamines are believed to exert their effects by binding to the monoamine transporters and increasing extracellular levels of the biogenic amines dopamine
, norepinephrine
, and serotonin
.
It is hypothesized that -amphetamine acts primarily on the dopaminergic (DA) systems, while -amphetamine is comparatively norepinephrinergic (NE). The primary reinforcing and behavioral-stimulant effects of amphetamine, however, are linked to enhanced dopaminergic activity, primarily in the mesolimbic dopaminergic pathway
. Amphetamine binds to the dopamine transporter (DAT) and blocks the transporter's 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 monoamine oxidase
-A and -B (MAO-A and MAO-B) in high doses. MAO-A is responsible for the breakdown of serotonin, dopamine, norepinephrine, and epinephrine. MAO-B is responsible for breaking down dopamine (more potently than MAO-A) and phenylethylamine (PEA), which has actions similar to those of 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 not 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: Amphetamine directly stimulates the release of these neurochemicals, resulting in a potent elevation in monoamine neurotransmission. In sum, the effect of amphetamines is to increase neurotransmitter
availability in the synapse
, by both releasing more neurotransmitters and prolonging their availability in the synapse by slowing their removal.
Many athletic organizations have restricted the usage of Adderall by athletes. The NCAA has banned the use of Adderall for its collegiate athletes without a prescription and adequate records of evaluation and diagnosis of ADHD. Nevada State Athletic Commission has also banned athletes in the state from using Adderall. Tim Credeur
was removed from a UFC fight on the finale of The Ultimate Fighter 7 because of a positive drug test due to his use of it. In the National Football League
, New Orleans Saints
kicker Garrett Hartley
served a four-game suspension when the 2009 NFL regular season began because he tested positive for the banned stimulant. The Arizona Cardinals
tight end Ben Patrick
received a four-game suspension as a result of using Adderall.
Shire introduced the Adderall brand in 1996 in the form of a multi-dose, instant-release tablet derived from an original formula of the weight management drug Obetrol
. In 2006, Shire agreed to sell rights to the Adderall name for this instant-release medication to Duramed Pharmaceuticals DuraMed Pharmaceuticals was acquired by Teva Pharmaceuticals in 2008 when Teva completed its acquisition of Barr Pharmaceuticals
(including Barr's Duramed division). Therefore, following its acquisition of Duramed, Teva is in the somewhat unusual position of manufacturing both a generic formulation of Adderall instant-release (under its Barr Division) as well as "brand name" Adderall (under its DuraMed division.)
Reflecting the change in manufacturers from Shire Pharmaceuticals to Teva's DuraMed Pharmaceuticals, the "imprint" on Adderall instant-release tablets has changed. One side of the instant-release tablets now bears the DuraMed Pharmaceuticals imprint, a lowercase letter "d" over a lowercase letter "p". This is a change from the previous uppercase "AD" imprint on the tablets.
The active ingredients of Adderall include a combination of dextroamphetamine
and racemic
-amphetamine salts. In 2001, Shire introduced an extended-release preparation of these ingredients in a variety of dosages under the brand name "Adderall XR," on which Shire retains exclusive patent rights until the patent expires, expected in 2018. However, due to issues with Shire's inability to evergreen (extend the patent life by obtaining either a new FDA indication or application of other patent life) the patent
for Adderall XR, the drug has become available in a generic form. In 2009, Barr and Shire reached a settlement agreement permitting Barr to offer a generic form of the drug beginning April 1, 2009.
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
salts–based medication used for attention-deficit hyperactivity disorder
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...
and narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
. It is a brand-name psychostimulant medication composed of racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...
amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
saccharide, and dextroamphetamine sulfate, which are all amphetamine salts. It is thought to work by increasing the amount of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
and norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
in the brain. In addition, the drug also acts as a potent dopamine reuptake inhibitor
Dopamine reuptake inhibitor
A dopamine reuptake inhibitor is a type of drug that acts as a reuptake inhibitor for the neurotransmitter dopamine by blocking the action of the dopamine transporter...
and norepinephrine reuptake inhibitor
Norepinephrine reuptake inhibitor
A norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...
. It is available in two formulations: IR (Instant Release) and XR (Extended Release). The immediate release formulation is indicated
Indication (medicine)
In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. The opposite of indication is contraindication.-Drugs:...
for use in Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
, while the XR formulation is approved for use only with ADHD.
Like other stimulant prescription drugs, Adderall directly affects the mesolimbic reward pathway in the brain. Amphetamine salts preparations are considered to have high abuse potential, and it is classified as Schedule II by the US DEA
DEA
DEA is the commonly used acronym for the Drug Enforcement Administration, a United States law enforcement agency.DEA or Dea may also refer to:- Organizations :* DEA , UK development education charity...
.
Medical uses
Adderall is used for attention-deficit hyperactivity disorderAttention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...
and narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
. It has been used to treat obesity, but The American Society of Health-System Pharmacists does not recommend this use.
Attention deficit hyperactivity disorder
Adderall has been shown to significantly reduce symptoms associated with attention-deficit hyperactivity disorderAttention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...
(ADHD), and in many patients it presents minimal side-effects. Depending on dosage, the beneficial effects of stimulant medications can last several hours, allowing improved performance throughout the day. Compared to the similar medication methylphenidate
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
(sold under the brand name Ritalin and others), studies have suggested that Adderall is slightly more potent and has a longer period of efficacy, especially at lower doses. For those who experience adverse side-effects to Ritalin or for whom Ritalin has become ineffective, Adderall is often recommended as a substitute.
For adolescents and adults, there is not adequate evidence that doses greater than 20 mg/day confer additional benefit,
although higher doses may be necessary due to variations in body weight.
Other
Apart from the FDA-approved indications for the treatment of ADHD and narcolepsy, Adderall has also been used off-label to manage cases of treatment-resistant depression and exogenousExogenous
Exogenous refers to an action or object coming from outside a system. It is the opposite of endogenous, something generated from within the system....
obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
.
Dosing and administration
Adderall is marketed as either an immediate-release tablet Adderall, or an extended-release capsule Adderall XR.Adderall XR utilizes the Microtrol
Microtrol
Microtrol is an extended-release drug delivery system. It is used in certain medications like Adderall and 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...
extended-release delivery system, incorporating 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
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
concentration is achieved in seven hours, compared to instant-release Adderall, which reaches maximum plasma concentration within three hours. As a result of its high bioavailability
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
, 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 900-calorie standard high-fat meal as the control). Medications that alter urinary pH will cause variations in the 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 US patent granted 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
Double-blind
A blind or blinded experiment is a scientific experiment where some of the people involved are prevented from knowing certain information that might lead to conscious or subconscious bias on their part, invalidating the results....
, placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
-controlled crossover study
Crossover study
A crossover study is a longitudinal study in which subjects receive a sequence of different treatments . While crossover studies can be observational studies, many important crossover studies are controlled experiments, which are discussed in this article...
conducted among 35 children ages 5–12 indicated that patients behaved similarly to those having taken other immediate-release amphetamines. The authors found that sustained-release dexamphetamine (the main isomeric-amphetamine component of Adderall) had a longer duration of action, however -amphetamine was less effective in the first few hours.
Adverse effects
Studies of long-term use of Adderall and methylphenidate in children have shown a temporary decrease in growth rate that does not affect final adult height. Stimulant medications also decrease appetite in some people, leading to weight loss, and this effect is more common with methylphenidate than Adderall methylphenidate or atomoxetine. Changes in vision have been reported with both Adderall and methylphenidate.
Women who are pregnant should avoid taking Adderall, especially during early pregnancy. Studies on rats show long-term neurological and behavioral changes resulting from prenatal and early postnatal exposure to amphetamines.
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.- MAOIs (monoamine oxidase inhibitorMonoamine oxidase inhibitorMonoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
s, e.g., phenelzinePhenelzinePhenelzine is a non-selective and irreversible monoamine oxidase inhibitor of the hydrazine class which is used as an antidepressant and anxiolytic...
, selegilineSelegilineSelegiline is a drug used for the treatment of early-stage Parkinson's disease, depression and senile dementia. In normal clinical doses it is a selective irreversible MAO-B inhibitor, however in larger doses it loses its specificity and also inhibits MAO-A...
, iproniazidIproniazidIproniazid is a hydrazine drug used as an antidepressant. It acts as an irreversible and nonselective monoamine oxidase inhibitor . Though it has been widely discontinued in most of the world, it is still used in France.- History :Iproniazid was the first antidepressant ever marketed...
, etc.) — Do not administer amphetamine for a minimum of two weeks after last use of MAOI type drug. High risk for hypertensive crisis. Preliminary trials of low-dose amphetamine and MAOIs being administered together are in progress. However, this is to be done only under strict supervision of the prescribing parties. - SSRIs (selective serotonin reuptake inhibitorSelective serotonin reuptake inhibitorSelective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...
s, e.g., fluvoxamineFluvoxamineFluvoxamine is an antidepressant which functions as a selective serotonin reuptake inhibitor . Fluvoxamine was first approved by the U.S. Food and Drug Administration in 1993 for the treatment of obsessive compulsive disorder . Fluvoxamine CR is approved to treat social anxiety disorder...
, citalopramCitalopramCitalopram brand names: Celexa, Cipramil) is an antidepressant drug of the selective serotonin reuptake inhibitor class. It has U.S...
, paroxetineParoxetineParoxetine is an SSRI antidepressant. Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline...
, etc.) — While a common combination, and although rare, the risk for serotonin syndromeSerotonin syndromeSerotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs...
exists. (Use only when directed) - NRIs (norepinephrine reuptake inhibitorNorepinephrine reuptake inhibitorA norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...
s, e.g., atomoxetine, etc.) — NRI medications and amphetamineAmphetamineAmphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
both enhance noradrenergic activity. Possible augmentation/potentiation of effects. (Use only when directed) - SNRIs (selective serotonin-norepinephrine reuptake inhibitorSerotonin-norepinephrine reuptake inhibitorSerotonin–norepinephrine reuptake inhibitors are a class of antidepressant drugs used in the treatment of major depression and other mood disorders...
s) — See SSRIs and NRIs. - BupropionBupropionBupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
— Both bupropion and amphetamine have noradrenergic and dopaminergic activity. Possible augmentation/potentiation of effects. Bupropion has pro-convulsant properties that may be enhanced or cumulatively potentiated by amphetamine. (Use only when directed) - Tricyclics and related compounds (tricyclic antidepressantTricyclic antidepressantTricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
) — See SNRIs and SSRIs. Possible potentiation of serotonin-, dopamine-, and norepinephrine-related drug effects. The combination of tricyclic and amphetamine compounds/other direct-acting sympathomimetics has been associated with increased sympathetic action. Adjustments to dose may be required. Concurrent use not generally recommended due to interaction between direct-acting sympathomimetics such as amphetamine and tricyclics. Indirect-acting sympathomimetics may have decreased efficacy when combined with tricyclics (tricyclic blockade may inhibit the action of some indirect-acting sympathomimetics). - CYP2D6 (liver enzyme) inhibitors, e.g., most SSRIs such as fluoxetine, citalopram, paroxetine, etc. Some anti-psychotics such as thioridazineThioridazineThioridazine is a piperidine typical antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis...
, haloperidolHaloperidolHaloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
, and levomepromazineLevomepromazineLevomepromazine in Germany and Methotrimeprazine in America is an aliphatic phenothiazine neuroleptic drug...
. The stimulantStimulantStimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
cocaineCocaineCocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
. The opioid agonist methadoneMethadoneMethadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
. There are additional drugs that inhibit CYP2D6. It is important to determine if any medication or drug taken is a CYP2D6 inhibitor. Taking a CYP2D6-inhibiting drug along with amphetamine will lead to an elevated level of amphetamine in the system, resulting in the drug's remaining in the body for a longer period, which can lead to undesirable and possibly serious side effects.
Pregnancy
FDA pregnancy category C. It is not known whether Adderall will harm an unborn baby. It could cause premature birth, low birth weight, or withdrawal symptoms in a newborn if the mother takes this medication during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.Government warnings
On February 9, 2005, Health CanadaHealth Canada
Health Canada is the department of the government of Canada with responsibility for national public health.The current Minister of Health is Leona Aglukkaq, a Conservative Member of Parliament appointed to the position by Prime Minister Stephen Harper.-Branches, regions and agencies: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. Further research found data suggesting use of Adderall resulted in an increased risk of cardiac defect. Although more than 37 million prescriptions for Adderall were filled during the four years prior, the U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
could find no increased risk of sudden death among Adderall users.
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
Black box warning
In the United States, a black box warning is a type of warning that appears on the package insert for prescription drugs that may cause serious adverse effects...
, 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. In September 2008, Britain's National Institute for Health and Clinical Excellence urged physicians not to prescribe Adderall or similar drugs to children under 5, and to exhaustively consider other approaches to behavioral modification before prescribing such drugs to children 5 and up.
Prolonged use
Prolonged high doses of amphetamines followed by an abrupt cessation can result in extreme fatigue, insomniaInsomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, irritability, and mental depression. Chronic abuse of amphetamines can result in the manifestation of amphetamine psychosis
Amphetamine psychosis
Stimulant psychosis is a psychotic disorder that appears in some people who use stimulant drugs. Most commonly, stimulant psychosis occurs in drug abusers who take very large doses but, in rare cases, it can also present in patients taking therapeutic doses under medical supervision...
.
Chemistry
Adderall's effects are similar to other CNSCentral nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
stimulants of the same class and preparation. (See amphetamine for details.)
Urinary and stomach pH levels can have a strong effect on -amphetamine excretion and absorption. An acidic stomach and GI pH will decrease the absorption of Adderall, and acidic urine levels will decrease the reabsorption of the drug through the renal system. Co-administration of acidic substances (e.g., citric acid
Citric acid
Citric acid is a weak organic acid. It is a natural preservative/conservative and is also used to add an acidic, or sour, taste to foods and soft drinks...
) causes decreased renal reabsorption of -amphetamine; whereas, alkaline agents (e.g., antacids) may cause a marked increase in renal tubular reabsorption. The increased reabsorption can increase the retention of amphetamines, with potential to result in dangerously high serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
levels.
Adderall XR
Adderall XR consists of the following amphetamineAmphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
compounds in equal proportions: dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
saccharate, dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
sulfate, racemic amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
aspartate monohydrate, and racemic amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
sulfate. Breakdown rates are affected by many factors including urinary and stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
, weight, gender, other medications being taken, and age. Alkalinity increases bioavailability, while acidity causes the drug to be excreted more quickly. Manufacturers claim that the mixture of salts in Adderall XR makes its effects smoother (that is, makes softer highs and lows). The mixture of salts and their ratios are as follows:
- 1/4 dextroamphetamine saccharate
- 1/4 dextroamphetamine sulfate
- 1/4 (racemic dextro/levo-)amphetamine aspartate monohydrate
- 1/4 (racemic dextro/levo-)amphetamine sulfate
These four salts are metabolized
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
at different rates and possess diverse half lives
Pharmacokinetics
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism...
, thereby resulting in a less dramatic onset and termination of therapeutic action, as compared to single-salt amphetamine preparations.
Metabolism
"The meanMean
In statistics, mean has two related meanings:* the arithmetic mean .* the expected value of a random variable, which is also called the population mean....
elimination half-life
Biological half-life
The biological half-life or elimination half-life of a substance is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity, as per the MeSH definition...
for d-amphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
is 10 hours in adults; 11 hours in adolescents aged 13–17 years and weighing less than or equal to 75 kg/165 lbs; and 9 hours in children aged 6 to 12 years. For the l-amphetamine
Levoamphetamine
Levoamphetamine is a psychostimulant known to increase wakefulness and focus in association with decreased appetite and fatigue. Levoamphetamine is the levorotary stereoisomer of the amphetamine molecule...
, the mean elimination half-life in adults is 13 hours; 13 to 14 hours in adolescents; and 11 hours in children aged 6 to 12 years. On a mg/kg body weight basis children have a higher clearance than adolescents or adults."
Generic forms
Both Adderall IR and Adderall XR are available in generic forms.The generic version of Adderall IR is available as generic drugs but the generic version of Adderall XR is only available as authorized generics
Authorized generics
Authorized generics are prescription drugs produced by brand pharmaceutical companies and marketed under a private label, at generic prices. Authorized generics compete with generic products in that they are identical to their brand counterpart in both active and inactive ingredients; whereas...
. Authorized generics are still manufactured by the brand name manufacturer but marketed and sold by a different company. Authorized generics are exactly the same as the brand name product both in active and inactive ingredients—they go through exactly the same brand manufacturing line, yet different labels are put on at the end of the manufacturing process.
Mechanism of action
Adderall’s inclusion of levoamphetamine provides the pharmaceutical with a quicker onset and longer clinical effect compared to pharmaceuticals formulated exclusively of dextroamphetamine.
Although it seems the human brain has a preference for dextroamphetamine over levoamphetamine, it has been reported that certain children have a better clinical response to levoamphetamine. Amphetamines are believed to exert their effects by binding to the monoamine transporters and increasing extracellular levels of the biogenic amines dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
, and serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
.
It is hypothesized that -amphetamine acts primarily on the dopaminergic (DA) systems, while -amphetamine is comparatively norepinephrinergic (NE). The primary reinforcing and behavioral-stimulant effects of amphetamine, however, are linked to enhanced dopaminergic activity, primarily in the mesolimbic dopaminergic pathway
Dopaminergic pathways
Dopaminergic pathways are neural pathways in the brain which transmit the neurotransmitter dopamine from one region of the brain to another.The neurons of the dopaminergic pathways have axons which run the entire length of the pathway...
. Amphetamine binds to the dopamine transporter (DAT) and blocks the transporter's ability to clear DA from the synaptic
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
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 monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...
-A and -B (MAO-A and MAO-B) in high doses. MAO-A is responsible for the breakdown of serotonin, dopamine, norepinephrine, and epinephrine. MAO-B is responsible for breaking down dopamine (more potently than MAO-A) and phenylethylamine (PEA), which has actions similar to those of 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 not substantial enough in duration and quantity to entail the need for a tyramine
Tyramine
Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent...
-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: Amphetamine directly stimulates the release of these neurochemicals, resulting in a potent elevation in monoamine neurotransmission. In sum, the effect of amphetamines is to increase neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
availability in the synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
, by both releasing more neurotransmitters and prolonging their availability in the synapse by slowing their removal.
Performance-enhancing use
Adderall is widely used as a "study drug" at many universities, due to Adderall's reported ability to help focus energy and concentration to a much higher level than normal. It enables the user to focus and stay awake. Stories of students writing papers continuously for an unusually long time or "cramming" all night for an exam with no loss of energy or concentration are common. College campuses known to be highly competitive or have a high rate of binge drinking had up to 25% of students use an ADHD medication within one year, a survey of students at 119 colleges across the country concluded.Many athletic organizations have restricted the usage of Adderall by athletes. The NCAA has banned the use of Adderall for its collegiate athletes without a prescription and adequate records of evaluation and diagnosis of ADHD. Nevada State Athletic Commission has also banned athletes in the state from using Adderall. Tim Credeur
Tim Credeur
Timothy Wallace Credeur II is an American mixed martial artist. He was a cast member of SpikeTV's The Ultimate Fighter 7 and was defeated by fellow cast member Jesse Taylor in the semi-finals. He was then brought back into the competition following the disqualification of Taylor. He fought C.B...
was removed from a UFC fight on the finale of The Ultimate Fighter 7 because of a positive drug test due to his use of it. In the National Football League
National Football League
The National Football League is the highest level of professional American football in the United States, and is considered the top professional American football league in the world. It was formed by eleven teams in 1920 as the American Professional Football Association, with the league changing...
, New Orleans Saints
New Orleans Saints
The New Orleans Saints are a professional American football team based in New Orleans, Louisiana. They are members of the South Division of the National Football Conference of the National Football League ....
kicker Garrett Hartley
Garrett Hartley
Garrett Hartley is an American football placekicker for the New Orleans Saints of the National Football League. He was signed by the Denver Broncos as an undrafted free agent in 2008...
served a four-game suspension when the 2009 NFL regular season began because he tested positive for the banned stimulant. The Arizona Cardinals
Arizona Cardinals
The Arizona Cardinals are a professional American football team based in Glendale, Arizona, a suburb of Phoenix. They are currently members of the Western Division of the National Football Conference in the National Football League...
tight end Ben Patrick
Ben Patrick
Ben Patrick is an American football tight end who is currently a free agent. He was drafted by the Arizona Cardinals in the seventh round of the 2007 NFL Draft. He played college football at Duke and Delaware....
received a four-game suspension as a result of using Adderall.
Detection of use
Amphetamine is frequently measured in hair, oral fluid, sweat, or urine as part of a drug abuse testing program. Techniques such as immunoassay may cross-react with a number of sympathomimetics drugs, so chromatographic methods specific for amphetamine should be employed to prevent false-positive results. Chiral techniques may be employed to help distinguish the source of the drug, whether obtained legally (by prescription) or illegally or possibly as a result of formation from a prodrug such as lisdexamfetamine or selegiline. Chiral separation can be used to differentiate Adderall use from use of another prescription form of amphetamine or from use of illicit amphetamine, since Adderall is unique in having a 3:1 mixture of the d- and l-isomers.History
Adderall is available as an instant-release (IR) and an extended-release (XR) drug. Adderall instant-release is manufactured today by Teva and Barr Pharmaceuticals. Shire Pharmaceuticals, the creator of Adderall IR, no longer produces it. However, Shire does continue to manufacture the extended-release version of Adderall ("Adderall XR").Shire introduced the Adderall brand in 1996 in the form of a multi-dose, instant-release tablet derived from an original formula of the weight management drug Obetrol
Obetrol
Obetrol is a pharmaceutical stimulant, amphetamine, used as an anorexiant to treat exogenous obesity with racemic amphetamine and methamphetamine salts...
. In 2006, Shire agreed to sell rights to the Adderall name for this instant-release medication to Duramed Pharmaceuticals DuraMed Pharmaceuticals was acquired by Teva Pharmaceuticals in 2008 when Teva completed its acquisition of Barr Pharmaceuticals
Barr Pharmaceuticals
Barr Pharmaceuticals was a global specialty pharmaceutical company that operated in more than 30 countries worldwide. Barr were engaged in the development, manufacture and marketing of generic and proprietary pharmaceuticals, biopharmaceuticals and active pharmaceutical ingredients.-History:Barr...
(including Barr's Duramed division). Therefore, following its acquisition of Duramed, Teva is in the somewhat unusual position of manufacturing both a generic formulation of Adderall instant-release (under its Barr Division) as well as "brand name" Adderall (under its DuraMed division.)
Reflecting the change in manufacturers from Shire Pharmaceuticals to Teva's DuraMed Pharmaceuticals, the "imprint" on Adderall instant-release tablets has changed. One side of the instant-release tablets now bears the DuraMed Pharmaceuticals imprint, a lowercase letter "d" over a lowercase letter "p". This is a change from the previous uppercase "AD" imprint on the tablets.
The active ingredients of Adderall include a combination of dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
and racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...
-amphetamine salts. In 2001, Shire introduced an extended-release preparation of these ingredients in a variety of dosages under the brand name "Adderall XR," on which Shire retains exclusive patent rights until the patent expires, expected in 2018. However, due to issues with Shire's inability to evergreen (extend the patent life by obtaining either a new FDA indication or application of other patent life) the patent
Patent
A patent is a form of intellectual property. It consists of a set of exclusive rights granted by a sovereign state to an inventor or their assignee for a limited period of time in exchange for the public disclosure of an invention....
for Adderall XR, the drug has become available in a generic form. In 2009, Barr and Shire reached a settlement agreement permitting Barr to offer a generic form of the drug beginning April 1, 2009.
Legal status
- JapanJapanJapan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
: Any medicine containing Methamphetamine or Amphetamine is defined as one of “Prohibited Stimulants” and strictly restricted in Japan. Nobody can bring any medicine containing Methamphetamine or Amphetamine (Adderall and so on) into Japan. - South KoreaSouth KoreaThe Republic of Korea , , is a sovereign state in East Asia, located on the southern portion of the Korean Peninsula. It is neighbored by the People's Republic of China to the west, Japan to the east, North Korea to the north, and the East China Sea and Republic of China to the south...
: Non-prescribed Amphetamine-based medications are banned in South Korea. They are illegal to import without a doctor's prescription. Adderall is not currently prescribed inside Korea, but other stimulant medications such as Ritalin are. - ThailandThailandThailand , officially the Kingdom of Thailand , formerly known as Siam , is a country located at the centre of the Indochina peninsula and Southeast Asia. It is bordered to the north by Burma and Laos, to the east by Laos and Cambodia, to the south by the Gulf of Thailand and Malaysia, and to the...
: Amphetamine and dextroamphetamine are classified as Type 1 Narcotics.