Adderall
649100
225919996
2008-07-16T00:45:53Z
69.50.51.164
/* Adderall abuse */ Amphetamine psychosis is it's own established condition, plus is much closer to psychotic mania than schizophrenic psychosis.
[[Image:AdderallXR-15mg.png|thumb|250px|Adderall XR 15 mg capsule]]
'''Adderall''' is a brand-name [[pharmacology|pharmaceutical]] [[psychostimulant]] or [[sympathomimetic amine]] composed of mixed [[amphetamine]] [[Salt (chemistry)|salts]]. The drug is used primarily to treat [[ADHD|attention-deficit hyperactivity disorder]] and [[narcolepsy]]. These are its only two approved indications. The Extended release formulation is not approved to treat narcolepsy.<ref>Shire US Inc., "Prescribing Information" sheet (PDF) for Adderall XR, March, 2007. Accessed May 1, 2008</ref>
==Other Uses==
Adderall has also been used successfully to manage severe cases of treatment-resistant [[Clinical depression|depression]]. Individuals who show little or no response to typical antidepressants--such as the SSRIs and tricyclics--are more likely to respond to psychostimulant therapy. These patients, however, are the exception, rather than the norm among those with depression and this is not an approved indication.
Other recognized uses include<ref>http://www.state.nj.us/oag/ca/pharm/pain.htm</ref>:
* Idiopathic Central Nervous System Hypersomnia established by recognized diagnostic criteria
* Drug-induced brain dysfunction
* Epilepsy
* Depression shown to be refractory to other therapeutic modalities
* Senile apathetic behavior
These above uses are not necessarily licenced in any particular country, for example they are not [[Food and Drug Administration|FDA]] approved in the USA.
==History==
[[Shire Pharmaceuticals]] 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]]<ref name="adderallxr">[http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/08-14-2006/0004416042 Press Release: Barr and Shire Sign Three Agreements], [[August 14]][[2006]], Accessed [[May 1]] [[2008]].</ref> and this instant-release medication has since become available in a [[generic formulation]] of "mixed [[amphetamine]] [[Salt (chemistry)|salt]]s"<ref name="rxlistamp">http://www.rxlist.com/cgi/generic/amphet.htm</ref>. The [[active ingredients]] of Adderall include a combination of [[dextroamphetamine]] and [[racemic]] {{sc||DL}}-amphetamine salts.<ref name=rxlistamp /> In 2001, [[Shire Pharmaceuticals]] introduced an [[extended-release]] preparation of these ingredients in a variety of dosages under the brand name "Adderall XR" (e'''<u>x</u>'''tended '''<u>r'''</u>elease), on which Shire retains exclusive patent rights until the patent expiry, expected in 2009.
==Chemistry==
Specifically, Adderall XR is composed of the following proportions of active ingredients<ref name="adderall_XR_rxinfo">Shire US Inc., "[http://www.adderallxr.com/assets/pdf/prescribing_information.pdf Prescribing Information" sheet] ([[PDF]]) for Adderall XR, March, 2007. Accessed [[May 1]], [[2008]]</ref>:
* 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 [[metabolism|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.<ref name=rxlistamp />
The average elimination half-life in adults for dextroamphetamine and levoamphetamine is 10 hours and 13 hours respectively. Breakdown rates are affected by many factors including [[urinary]] and [[stomach]] [[pH]], weight, gender, other medications being taken, and age.
Urinary and stomach pH levels can have the strongest effect on {{sc||DL}}-amphetamine excretion and absorption. Co-administration of acidic substances (e.g. [[citric acid]]) causes an accelerated excretion of {{sc||DL}}-amphetamine while co-administration of alkaline agents (e.g. [[antacids]]) causes a marked increase in both retention and absorption of amphetamines potentially resulting in dangerously high [[serum]] amphetamine levels.
Adderall's effects are similar to other [[central nervous system|CNS]] stimulants of the same class and preparation (see [[amphetamine#Effects|amphetamine]] for details).
==Dosing and administration==
Adderall is marketed as either an immediate-release tablet, Adderall, or an extended-release capsule, Adderall XR ("E'''x'''tended '''R'''elease"). Doses for both Adderall XR and Adderall are 5, 10, 15, 20, and 30 [[milligram]] strengths with instant-release Adderall having two extra ones, 7.5 and 12.5 milligrams, and Adderall XR having a 25 milligram dose.{{Fact|date=May 2008}}
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 [[Blood plasma|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 amount and method of excretion and usage should be monitored when taken concurrently with Adderall.{{Fact|date=May 2008}}
Manufacturer's claims of instant release have been disputed. A US patent granted for Adderall<ref>{{US patent reference
| number = 6384020
| y = 2002
| m = 05
| d = 07
| inventor = Flanner, Henry H., et al.
| title = A pharmaceutical composition comprising lactitol and one or more amphetamine salts in a rapid release formulation
}}</ref> 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 {{sc||D}}-amphetamine was less effective in the first few hours.<ref>http://www.healthsystem.virginia.edu/internet/pediatrics/pharma-news/v8n3.pdf</ref>
==Use as treatment for attention-deficit/hyperactivity disorder (ADHD)==
Adderall has been commonly prescribed for many years as a treatment for children and adults with attention deficit/hyperactive disorder ([[ADHD]]), a disorder that prevents children and adults from being able to focus on tasks for extended periods of time, a particularly detrimental condition for school performance. After administration of Adderall students have been shown to give higher teacher ratings and perform better in mathematics within 1.5 hours of initial dose. Depending on dosage, these beneficial effects can also last several hours allowing improved performance throughout the day.<ref>Swanson, et al., Analog Classroom Assessment of Adderall(R) in Children With ADHD, Journal of the American Academy of Child & Adolescent Psychiatry. 37(5):519-526, May 1998.</ref><ref>Biederman, et al., A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of SLI381 (Adderall XR) in Children With Attention-Deficit/Hyperactivity Disorder, PEDIATRICS Vol. 110 No. 2 August 2002, pp. 258-266</ref>
Other studies comparing Adderall with other similar medications have shown that Adderall is also more potent than [[Ritalin]] (methylphenidate) and has a longer period of efficaciousness. For many this means it is likely preferable as a medication for ADHD, and certainly a substitute for children who have adverse side effects to Ritalin, or for whom Ritalin has become ineffective.<ref>Pelham, et al., A Comparison of Ritalin and Adderall: Efficacy and Time-course in Children With Attention-deficit/Hyperactivity Disorder, PEDIATRICS Vol. 103 No. 4 April 1999, p. e43</ref><ref>Pliszka, et al., A Double-Blind, Placebo-Controlled Study of Adderall and Methylphenidate in the Treatment of Attention-Deficit/Hyperactivity Disorder, Journal of the American Academy of Child & Adolescent Psychiatry. 39(5):619-626, May 2000.</ref>
There are also other reasons for taking Adderall aside from just alleviating the symptoms of ADHD. Untreated ADHD has been linked to an increased risk of psychoactive substance abuse later in life.<ref>Biederman, et al., Is ADHD a Risk Factor for Psychoactive Substance Use Disorders? Finding From a Four-Year Prospective Follow-Up Study, FOCUS 1:196-204 (2003)</ref>Fortunately, the likelihood of a drug abuse disorder can be approximately halved by proper treatment during childhood. For many, these stimulant medications used to treat ADHD actually provide protection against developing other drug dependencies in this increased risk population. This contradicts the commonly held misconception that use of drugs like Adderall or Ritalin can cause increased drug dependency later in life.<ref>Wilens, et al., Does Stimulant Therapy of Attention-Deficit/Hyperactivity Disorder Beget Later Substance Abuse? A Meta-analytic Review of the Literature, PEDIATRICS Vol. 111 No. 1 January 2003, pp. 179-185</ref>
However, specialists also stress the need for ADHD treatments not to solely rely on drugs like Adderall. They advise a comprehensive treatment plan that includes ADHD education, coaching and support groups; regular visits to your doctor; therapy or counseling regarding ADHD; involvement in recovery programs, and family and relationship counseling when appropriate.<ref>Richardson, AD/HD and Stimulant Medication Abuse, adapted from The Link Between ADD & Addiction, Getting the Help You Deserve, (1997) Piñon Press, and When Too Much Isn't Enough, Ending The Destructive Cycle of AD/HD and Addictive Behavior, released in January (2005) Piñon Press</ref>
==Generic equivalents/alternatives==
Until recently, the closest generic equivalent to Adderall (which uses racemic mixed amphetamine salts) was [[dextroamphetamine sulfate]] also known as [[Dexadrine]] and available in a [[sustained release]] form called Dexedrine ER. As of 2008, mixed amphetamine salts are available as a generic formulation<ref name="drugstoreamp"> [http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=00555076702&trx=1Z5006 Drugstore.com Brand and Generic Prices for Adderall]</ref>. It should be noted that Dexadrine is a single salt form of D-amphetamine, therefore Dexedrine and Dexedrine ER are not strict generic equivalents for Adderall and Adderall XR, though they may, in terms of physiological and psychological effects, be a ''[[de facto]]'' generic alternative. The savings between Adderall XR and generic Dexedrine ER are significant: 90 ''dextroamphetamine extended-release'' capsules cost $20 at a retail [[pharmacy]] in the [[United States]], while the equivalent 90 Adderall XR capsules cost $270. The difference is due to the fact that Adderall XR has been protected under patent in the United States. Until this patent expires, generic versions of Adderall XR will not become available. The generic formulation of Adderall, however, marketed as "mixed amphetamine salts" or "d-amphetamine salt combo," carry a significant savings over that of branded Adderall. On average, Adderall runs about $330 per 100 doses (or $3.30 per dose), whereas the generic mixed amphetamine salts are about one third as expensive - running about $120 per 100 doses (or a little more than $1 per dose).<ref name=drugstoreamp />
[[Vyvanse]] is another alternative which is actually a [[prodrug]] (precursor) of [[Dextroamphetamine]]. It behaves differently in the body than other formulations of amphetamines due to the fact that in its parent form is is not directly biologically active as an amphetamine (see [[Dextroamphetamine#Formulations|Dextroamphetamine at "Formulations"]]). Pharmaceutical companies use strategies such as this in order to patent allegedly "improved" products that are similar to previous agents yet cannot be produced generically for the time being or offer some other "benefit".
==Mechanism of action==
{{main|Dextroamphetamine#Mixed_amphetamine_salts}}
Adderall’s inclusion of levoamphetamine provides the pharmaceutical with a quicker onset and longer clinical effect compared to pharmaceuticals exclusively formulated of dextroamphetamine<!--
-->.<ref>{{cite journal | author = Glaser, ''et al.'' | title = Differential Effects of Amphetamine Isomers on Dopamine in the Rat Striatum and Nucleus Accumbens Core | journal = Psychopharmacology | volume = 178 | pages = 250–258 (Pages: 255,256) | year = 2005 | doi = 10.1007/s00213-004-2012-6}}</ref>
Although it seems that where the human brain has a preference for dextroamphetamine over levoamphetamine, it has been reported that certain children have a better clinical response to levoamphetamine<!--
-->.<ref name="Arnold">{{cite journal | author = Arnold | title = Methylphenidate vs Amphetamine: Comparative Review | journal = Journal of Attention Disorders | volume = 3 | issue = 4 | pages = 200–211| year = 2000 | doi = 10.1177/108705470000300403}}</ref>
<!--
This section is WAAY too confusing for people who are looking to understand adderall. We must assume people looking at this page are not chemists or biologists but rather people who were just prescribed it or want to use it for whatever purpose. Thus this section needs a complete rewrite to be comprehendable to that audience. Until then, a simple [non-complete] explanation will have to do.
AND none of this is properly sourced!
Amphetamines, both as dextroamphetamine and levoamphetamine (or a racemic mixture of the two enantiomers), 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 {{sc||D}}-amphetamine acts primarily on the dopaminergic systems, while {{sc||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 [[monoamine oxidase]] A and B (MAO-A and MAO-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]] (PEA), which 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.-->
==Side effects==
====In children====
* Decreased appetite<ref name=adderall_XR_rxinfo />
* Difficulty falling asleep<ref name=adderall_XR_rxinfo />
* Stomach ache<ref name=adderall_XR_rxinfo />
* [[Emotional lability]]<ref name=adderall_XR_rxinfo />
* Premature puberty<ref name=adderall_XR_rxinfo />
====In adults====
* Dry mouth<ref name=adderall_XR_rxinfo />
* Loss of appetite<ref name=adderall_XR_rxinfo />
* Difficulty falling asleep<ref name=adderall_XR_rxinfo />
* Weight loss {{Fact|date=June 2008}}
* Symptoms of depression/anxiety {{Fact|date=June 2008}}
* Skin Peeling {{Fact|date=June 2008}}
====From overdose====
These symptoms require immediate medical assistance:
*Symptoms of [[tourettism]]<ref name=adderall_XR_rxinfo />
*[[Seizure]]s or abnormal [[Electroencephalography|EEGs]]<ref name=adderall_XR_rxinfo />
*[[Hypertension|High blood pressure]]<ref name=adderall_XR_rxinfo />
*[[Tachycardia]]
*Swelling of hands/feet/ankles (for example, numbing of the fingertips)
*Delusions
*Hallucinations
*Sweating
*Vomiting
*Intense Dehydration
*Muscle Pain
*Lower abdominal 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 result in the manifestation of [[amphetamine psychosis]].<ref name="adderall_XR_rxinfo" />
=== 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 inhibitor]]s, e.g., [[Fluoxetine]], [[Citalopram]], [[Paroxetine]], etc.) — While rare, the possibility for [[serotonin syndrome]] exists with this combination. Use only when it is directed.
*NRIs ([[norepinephrine reuptake inhibitor]]s, e.g., [[Atomoxetine]], Strattera, etc.) — NRI medications and [[amphetamine]] both enhance noradrenergic activity. Possible augmentation/potentiation of effects. Use only when directed.
*SNRIs (selective [[serotonin-norepinephrine reuptake inhibitor]]s) — See SSRIs and NRIs.
*[[Bupropion]] (Zyban, Wellbutrin IR, ~SR, ~XL, etc.) — 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. Use only when directed.
*MAOIs ([[monoamine oxidase inhibitor]]s, e.g., [[Phenelzine]], Nardil, [[Selegiline]], Emsam, [[Iproniazid]], Iprozid, etc.) — Do not administer amphetamines for a minimum of two weeks after last use of MAOI type drug. Possible hypertensive crises, dangerously elevated amphetamine levels. Preliminary trials of low dose amphetamine and MAOIs being administered together are in progress. However, this is to only be done under strict supervision of the prescribing parties.
*Tricyclics and related compounds ([[tricyclic antidepressant]]s, e.g., [[Imipramine]], Tofranil, Janamine; as well as related compounds including [[Cyclobenzaprine]]) — See SNRIs and SSRIs. Possible potentiation of 5htp (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 amphetamines and tricyclics. Indirect acting sympathomimetics may have decreased efficacy when combined with tricyclics (tricyclic blockade may inhibit the action of some indirect acting sympathomimetics).
==Performance-enhancing use==
Due to side effects including appetite suppression and weight loss, Adderall has also been used as an [[off-label use|off-label]] drug for obesity.<ref>[http://www.msnbc.msn.com/id/15385195/ Quick-fix diet drugs: Effective or harmful? - Eating Well - MSNBC.com<!-- Bot generated title -->]</ref>
Adderall is also reportedly widely used as a "study drug" at many American universities. Adderall is reported to help focus energy and concentration to a much higher level than normal. It enables the user to focus and stay awake.<ref name="twohey">Twohey, Megan. "Pills become an addictive study aid: At colleges, students take a deadly risk by abusing ADHD drug." ''Knight Rider Tribune Business News.'' 26 March 2006: 1.</ref> Stories of students writing papers for an unusual number of continuous hours [e.g., 14 hours], or cramming all night for an exam with no loss of energy or concentrations are common. However, the user reportedly can suffer from drastic side effects the following day if Adderall was used to avoid a normal sleep pattern. These reported side effects include temporary loss of vision, sleeping over 14 hours, muscle spasms, vomiting, mental confusion, etc. William Frankenberger, psychology professor at University of Wisconsin at Eau Claire, led at a study at the university in 2004 that reported 14% of the campus had abused some form of ADHD drug, including Adderall.<ref name="twohey"/>. College campuses known to be highly competitive or have a high rate of binge drinking had up to 25% of students who misused an ADHD medication within one year, a survey of students at 119 colleges across the country concluded.<ref name="twohey">. Other forms of ADHD medication used as a performance enhancing drug include Ritalin, Concerta, and Dexedrine.<ref>Monson, PharmD, Kristi and Schoenstadt, MD, Arthur. "Alternatives to Adderall." 10 April 2008. http://adhd.emedtv.com/adderall/alternatives-to-adderall-p2.html</ref>.
==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.<ref>[http://www.fda.gov/cder/drug/advisory/adderall.htm Public Health Advisory for Adderall and Adderall XR<!-- Bot generated title -->]</ref> Further research found data suggesting use of Adderall resulted in an increased risk of cardiac defect. 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.<ref> Ibid. </ref><ref>[http://www.webmd.com/content/article/100/105792.htm Sudden Death in 12 Kids on ADHD Drug Adderall<!-- Bot generated title -->]</ref>
In August 2005, Health Canada followed the committee report of three independent physicians and lifted the ban on Adderall XR.<ref>[http://hc-sc.gc.ca/dhp-mps/prodpharma/activit/new-drug-com-nouvelle-drogue/ndca_rep_cnma_rap_2005-08-25_e.html Report of the Adderall XR New Drug Committee<!-- Bot generated title -->]</ref><ref>[http://pn.psychiatryonline.org/cgi/content/full/40/19/2 Canada Reverses Ban On ADHD Medication - Rosack 40 (19): 2 - Psychiatr News<!-- Bot generated title -->]</ref> 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.<ref>[http://www.drthomasebrown.com/resources/newsletters/may06.html Resources for Information about ADD/ADHD and Related Disorders<!-- Bot generated title -->]</ref> 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.<ref>[http://www.fda.gov/cder/drug/InfoSheets/patient/adderallPT.htm Patient Information Sheet for Adderall<!-- Bot generated title -->]</ref> 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.<ref>[http://www.washingtonpost.com/wp-dyn/content/article/2006/03/22/AR2006032202079.html Dire Warning Not Urged for ADHD Drugs - washingtonpost.com<!-- Bot generated title -->]</ref> A Black Box Warning regarding amphetamine abuse potential is in place, however.
==Notes and references==
{{reflist}}
==Further reading==
*Hanna, Mohab "Making the Connection: A Parent's Guide to Medication in ADHD" Ladner-Drysdale 2006
{{stimulants}}
[[Category:Amphetamines]]
[[Category:Sulfates]]
[[Category:Nootropics]]
[[pl:Adderall]]
[[tr:Adderall]]