Adderall
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Adderall 25 mg XR Capsules
Adderall 25 mg XR Capsules
Adderall® CII is a pharmaceutical stimulant amphetamine used to treat attention-deficit hyperactivity disorder and narcolepsy. Severe cases of depression may also be treated with Adderall or other stimulants. It was first prescribed in the 1920s as an anorectic (under the brand name Obetrol®), but such usage is now rare.
Use
Adderall was introduced in 1996 as instant-release tablets, which has since become available as the generic formulation "mixed amphetamine salts." The active ingredients of Adderall include a combination of dextroamphetamine and racemic amphetamine salts. Shire later introduced a gradual-release preparation of these ingredients, Adderall XR (extended release), and retains patent rights on Adderall XR that will expire in 2007.
In particular, Adderall XR is comprised of the following proportions of active ingredients:
* 1/4 Dextroamphetamine Saccharate
* 1/4 Dextroamphetamine Sulfate
* 1/4 dl-amphetamine Aspartate (racemic amphetamine)
* 1/4 dl-amphetamine Sulfate (racemic amphetamine)
The four component salts are claimed to be metabolised at different rates, thereby imparting a more gradual and "smoother" build-up and decline in effect compared to amphetamine preparations comprising only a single salt.
The average elimination half-life for dextroamphetamine is 10 hours in adults, and for levoamphetamine, 13 hours. Its effects are otherwise similar to other central nervous system stimulants (see amphetamine for details.).
The manufacturer claims that the mixture of salts makes Adderall's effects smoother, with softer highs and lows, than those of other treatments for the same disorders.
There is little evidence, however, to support this claim for immediate-release. A recent patent application for Adderall (USP #6,384,020) 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, and cost less than Adderall, though dexamphetamine was less effective in the first few hours.[1]
Adderall is now sold in either an immediate-release tablet or an extended-release capsule, marketed as Adderall XR (for "eXtended Release"). Doses for both immediate-release and extended-release form come in 5, 10, 15, 20, 25 and 30 mg increments.
Adderall XR utilizes the Microtrol® delivery system to achieve the extended-release mechanism. This delivery system incorporates two beads: the first type of bead dissolves immediately and the second type releases four hours later. Maximum plasma concentration is achieved in seven hours, compared to regular Adderall IR (immediate-release) which reaches maximum plasma concentration within three hours. As a result of its high bioavailability, Adderall XR's effectiveness is not altered by food absorption in the gastrointestinal tract. However, tmax (mean plasma concentration) is prolonged by 2.5 hours (using a standard high-fat meal as the control). Acidic beverages should not be ingested with Adderall XR as they alter the pH balance of the stomach.[2]
[edit] Effects
While the exact mechanism is unknown, it is believed that Adderall works by blocking the reuptake of dopamine and norepinephrine into the presynaptic neuron and increasing their release from the presynaptic neuron into the extraneuronal space. In other words, Adderall reverses the reuptake mechanism, turning it into a pump instead of a vacuum. Sources note that amphetamine and related compounds (ephedrine, etc.) displace noradrenaline from the presynaptic neuron and do not act as reuptake inhibitors as referenced above. [citation needed]
The increased flow of dopamine and norepinephrine into the extraneuronal space causes the patients' brain, as one psychiatrist explains,[citation needed] to experience a more intense level of concentration, causing an increased ability to focus for extended periods of time, and a heightened interest in performing focus based tasks.
Some patients feel they are less creative while taking Adderall, while others report that it can aid in creative work.[citation needed] The famous Beat generation writer Jack Kerouac, for instance, is said to have written much of his classic On The Road in a span of three weeks, aided by amphetamine (an active ingredient in Adderall) from Benzedrine inhalers; country music star Johnny Cash had a long period of amphetamine use in the 1960s; and mathematician Paul Erdős was noted for habitual use of prescription amphetamine throughout the final decades of his life; Smile was written by Brian Wilson and Van Dyke Parks with heavy amphetamine use, among others. All of these probably knew the drug by its common name, speed.
Double-blind, placebo-controlled studies of dextroamphetamine in normal subjects have shown significant performance increases on cognitive tasks and decreased reaction time. http://www.sciencemag.org/cgi/content/abstract/199/4328/560
Amphetamines have been shown to pass through into breast milk. Because of this, mothers taking medications containing amphetamines are advised to avoid nursing during their course of treatment. (http://www.fda.gov/cder/foi/label/2004/021303s005lbl.pdf)
[edit] Side effects
Common side effects of Adderall used as prescribed include: dry mouth, loss of appetite, difficulty falling asleep, headache, and weight loss.
Less common side effects
Some information in this article or section has not been verified and may not be reliable.
Please check for inaccuracies, and modify and cite sources as needed.
Less common side effects of Adderall used as prescribed include:Upset stomach,Nervousness, Mydriasis, Bruxism (teeth grinding), Urinary retention, Pyrexia, Tachycardia, Tics, Urticaria, Erectile Disorder, Increased urination, Blunted affect
[edit] Rare side effects
Some information in this article or section has not been verified and may not be reliable.
Please check for inaccuracies, and modify and cite sources as needed.
Rare side effects of Adderall used as prescribed include:Amphetamine psychosis[citation needed], high blood pressure, tourettism[citation needed], cardiomyopathy[citation needed], and hair loss[citation needed].
[edit] Contraindications
Using any amphetamine, (including Adderall, methamphetamine or MDMA) within 1-2 weeks of taking a monoamine oxidase inhibitor (MAOI) can cause a potentially fatal condition known as serotonin syndrome.
[edit] Performance-enhancing use
Because Adderall uses amphetamine stimulants to help the user concentrate for extended periods of time, many students today request Adderall from doctors in order to use it as a study aid. Thus, it is increasingly popular on college campuses. The largest benefit to students, however, is Adderall's ability to give students the power to focus on and learn what would usually be uninteresting material. Because of the appetite-suppressing properties of amphetamines, it is also sought after by those wishing to lose weight. Another less common use for students is to take Adderall before or during a night of heavy drinking in order to remain alert and active despite being intoxicated.
Research done by the National Institute of Drug Abuse (NIDA) shows the more competitive the college, the higher the incidence of stimulant use. An article published stated the findings of a nationwide survey of thousands of college students[3]. The findings of this past April 2006 survey shows 5.9% use rates among the more competitive campuses, compared to 1.3% use rates among less competitive campuses. Breaking down the use pattern even further, this same sample done by NIDA reveals whites were more likely to use stimulants compared to African Americans and Asians, at rates of 4.9%, 1.6%, and 1.3% respectively. Further, students with lower grade point averages of B’s or below use stimulants at a rate of 5.2%, compared to students earning B+ or above who use this medication at rates of only 3.3%. This research also specifically identified that students involved in sororities or fraternities use stimulants at a much higher rate of 8.6% compared to nonmembers who reported use at rates of only 3.3% (Whitten, 6).
Another major concern about the use of Adderall among college students is the psychological dependence that may cause students to lose faith in their own ability to perform well and the dependence on the advantageous effects of stimulant medication. Jackie Kurta, an Alcohol and Drug Specialist at UC Santa Barbara’s Student Heath Services states, “Students start out taking study drugs one time to study. The drugs work so well that the students begin to lose confidence in their own abilities to study without them,” (Hirschey).
The black market price of Adderall varies widely. Prices frequently range between $3 to $10 a pill. With pills ranging from 5 to 35 mg. However pills may sell for as little as $.20 or as much as $25.
Aside from being used by college students as a study aide, Adderall has been used as an off label drug for weight loss. Adderall’s side effect of weight loss and appetite suppression is a desired result for those trying to lose weight. It is administered as part of a “cocktail” of other off label prescription drugs that have side effects used to treat obesity. There have not been any scientific studies performed to evaluate the effectiveness of this form of treatment and is viewed a very risky and potentially dangerous way to shed pounds. (http://www.msnbc.msn.com/id/15385195/)
[edit] 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 1999 to 2003. [4]. Further research, however, found little data suggesting use of Adderall resulted in an increased risk of cardiac defect. Of the twelve sudden deaths positively linked to pediatric Adderall users during the four year period, five had known pre-existing cardiac conditions, one died after strenuous exercise in 110 degree heat and two had levels suggestive of an overdose. Given the more than 37,000,000 prescriptions for Adderall filled during the four years, the US Food and Drug Administration could find no increased risk of sudden death among Adderall users beyond the normal rate of the general population. [5], [6] In August, 2005, Health Canada followed the committee report of three independent physicians and lifted the ban on Adderall XR. [7], [8] Given that persons with AD/HD are a high risk group, it has been suggested that stimulant medications for persons with AD/HD will actually result in lower incidence of premature death. [9]
Currently the FDA and Health Canada advise against the use of Adderall in those persons with pre-existing cardiac or mental illnesses. They also suggest against its use in persons who have a history of drug abuse. [10] 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. [11] A Black Box Warning regarding amphetamine abuse potential is in place, however.
Indicated for:
* ADD
* ADHD
* narcolepsy
Recreational uses:
* Stimulant / "Speed" / "Uppers"
Other uses:
* treatment-resistant depression
* appetite suppressant
* antidepressant augmentation
Contraindications:
* Use of tricyclic antidepressants (e.g. desipramine), as MPH may dangerously increase their plasma concentrations, leading to potential toxic reactions (mainly, cardiovascular effects).
* Use of MAO Inhibitors, such as phenelzine (Nardil) or tranylcypromine (Parnate), and certain other drugs.
* MPH should not be given to patients who suffer from the following conditions: Severe Arrhythmia, Hypertension or Liver damage.
* Drug-seeking behaviour
* Pronounced agitation or nervousness
Side effects:
Atypical sensations:
* ?
Cardiovascular:
* Tachycardia
* Arterial hypertension
Ear, nose, and throat:
* ?
Endocrinal:
* Appetite loss
Eye:
* Blurred vision
* Pupil dilation (If snorted)
Gastrointestinal:
* Nausea/vomiting, abdominal pain
Hematological:
* ?
Musculoskeletal:
* Muscle twitches
Neurological:
* Insomnia, drowsiness, dizziness, headache
Psychological:
* Nervousness
* Euphoria
Respiratory:
* Increased respiration rate
Skin:
* ?
Urogenital and reproductive:
* ?
Miscellaneous:
* ?
Methylphenidate (MPH) is an amphetamine-like prescription stimulant commonly used to treat Attention Deficit Hyperactivity Disorder (ADHD) in children and adults. It is also one of the primary drugs used to treat symptoms of traumatic brain injury and the daytime drowsiness symptoms of narcolepsy and chronic fatigue syndrome. Brand names of drugs that contain methylphenidate include Ritalin® (Ritalina®, Rilatine®, Ritalin LA® (Long Acting)), Attenta®, Concerta® (a timed-release capsule), Metadate®, Methylin® and Rubifen®. Focalin® is a preparation containing only dextro-methylphenidate, rather than the usual racemic dextro- and levo-methylphenidate mixture of other formulations. A newer way of taking meythlphenidate is by using a patch (Daytrana®), similar to those used for birth control and nicotine release.
History
Methylphenidate was patented in 1954 by the Ciba pharmaceutical company (one of the predecessors of Novartis) and was initially prescribed as a treatment for depression, chronic fatigue, and narcolepsy, among other ailments. Beginning in the 1960s, it was used to treat children with ADHD, known at the time as hyperactivity or minimal brain dysfunction (MBD). Today methylphenidate is the medication most commonly prescribed to treat ADHD around the world. According to most estimates, more than 75 percent of methylphenidate prescriptions are written for children, with boys being about four times as likely to take methylphenidate as girls. Production and prescription of methylphenidate rose significantly in the 1990s, especially in the United States, as the ADHD diagnosis came to be better understood and more generally accepted within the medical and mental health communities. Methylphenidate has been used illegally by students for whom the drug has not been prescribed, to assist with coursework and examinations.[1]
While ADHD medication is directed for children, it has not been studied for children under the age of 6. It is also important to note that while ADHD is a condition that includes hyperactivity, problems holding still, and following directions, this is also typical of a child under the age of 6. This causes difficulty in diagnosing children under this age and should probably not be studied.[2]
Most brand-name Ritalin is produced in the United States, although methylphenidate is also produced in Mexico and Argentina by respective contract pharmaceutical manufacturers and is most commonly marketed under the brand name "Ritalin" for Novartis. In the United States, various generic forms of methylphenidate are also produced by several pharmaceutical companies (such as Methylin, etc.), and Ritalin is also sold in the United Kingdom, Germany, and other European countries (although in much lower volumes than in the United States). These generic versions of methylphenidate tend to outsell brand-name "Ritalin" four-to-one. In Belgium the product is sold under the name "Rilatine" for Novartis.
Another medicine is Concerta, a once-daily extended release form of methylphenidate, which was approved in April 2000. Studies have demonstrated that long-acting methylphenidate preparations such as Concerta are just as effective, if not more effective, than IR (instant release) formulas.[3][4][5][6] Time-release medications are also harder to misuse.
In April 2006, the FDA approved a transdermal patch for the treatment of ADHD, called Daytrana. The once-daily patch administers methylphenidate in doses of 10, 15, 20, or 30mg.[7] However, the patch must be applied several hours before the effect is desired, and the drug's effect remains for several hours after removal, making it necessary to remove the patch in the mid-to-late afternoon or else insomnia may result.
Effects
Methylphenidate is a central nervous system (CNS) stimulant. It is claimed to have a 'calming' effect on many children who have ADHD,[8] reducing impulsive behavior and the tendency to "act up", and helps them concentrate on schoolwork and other tasks. Adults who have ADHD often claim that MPH increases their ability to focus on tasks and organize their lives.
Methylphenidate has been found to have a lower incidence of side-effects compared to dextroamphetamine, a less commonly prescribed medication.[9] When prescribed at the correct dosage, methylphenidate is usually well-tolerated by patients.[3]
The means by which methylphenidate helps people with ADHD are not well understood. Some researchers have theorized that ADHD is caused by a dopamine imbalance in the brains of those affected. MPH is a dopamine reuptake inhibitor, which means that it increases the level of the dopamine neurotransmitter in the brain by partially blocking the transporters that remove it from the synapses.[10] An alternate explanation which has been explored is that the MPH affects the action of serotonin in the brain[11].
In the United States, methylphenidate is classified as a Schedule II controlled substance, the designation used for substances that have a recognized medical value but which have a high potential for abuse because of their addictive potential. Internationally, methylphenidate is a Schedule II drug under the Convention on Psychotropic Substances.[12]
[edit] Side effects
Commonly reported side effects include difficulty sleeping (which can lead in turn to other problems), loss of appetite (thus its use as an appetite suppressant), depression, irritability, nervousness, stomach aches, headaches, dry mouth, blurry vision, nausea, pupil dilation, dizziness, drowsiness, and motor tics or tremors [13][14].
Less common side effects include hypersensitivity, anorexia, palpitations, blood pressure and pulse changes, cardiac arrhythmia, anemia, scalp hair loss, bruxism (teeth grinding), jaw clenching and toxic psychosis.[citation needed]
There have also been reports of abnormal liver function, cerebral arteritis, leukopenia, and death.[citation needed]
A more comprehensive list of rare side-effects may be found on Medline.[15]
[edit] Long-term Effects
[edit] Brain and body
In a 2005 study, only "minimal effects on growth in height and weight were observed" after 2 years of treatment. "No clinically significant effects on vital signs or laboratory test parameters were observed." [16]
Still, some theoretical studies have raised questions. For example, Adriani et al (2005) found plastic changes in reward related behavior in rats after they were in a drug-free state.[17] MPH may or may not have similar effects on human cognition.
A 2006 review assessing the safety of MPH on the developing brain found that in animals with psychomotor impairments (such as ADHD), structural and functional parameters of the dopamine system were improved with treatment [18]. This indicates that in subjects with ADHD, MPH treatment may positively support brain development.
A 2003 study tested the effects of d-methylphenidate (Focalin), l-methylphenidate, and d, l-methylphenidate (Ritalin) on mice to search for any carcinogenic effects. The researchers found that all three compounds were non-genotoxic and non-clastogenic; d-MPH, d, l-MPH, and l-MPH did not cause mutations or chromosomal aberrations. They concluded that none of the compounds present a carcinogenic risk to humans.[19].
In February 2005, a team of researchers from The University of Texas M.D. Anderson Cancer Center led by R.A. El-Zein announced that a study of 12 children indicated that methylphenidate may be carcinogenic. In the study, 12 children were given standard therapeutic doses of methylphenidate. At the conclusion of the 3 month study, all 12 children displayed significant, treatment induced chromosomal aberrations. The researchers indicated that while their study was relative small, they indicated the results should be reproduced one more time in a bigger population for a definitive conclusion about the genotoxicity of methylphenidate to be drawn. [20] This is the first study of this kind ever performed in humans.
[edit] Stature
Researchers have also looked into the role of methylphenidate in affecting stature, with some studies finding slight decreases in height acceleration.[21] Other studies indicate height may normalize by adolescence.[22][23]
[edit] Risk of death
There have been at least 19 cases of sudden death in children taking methylphenidate, leading to calls by the Drug Safety and Risk Management Advisory Committee to the FDA to require the most serious type of health warning on the label, but this advice was rejected (New Scientist 18 Feb. 2006).
On February 9, 2006, the Drug Safety and Risk Management Advisory Committee of the Food and Drug Administration (FDA) voted by a margin of eight to seven to recommend a "black-box" warning describing the cardiovascular risks of stimulant drugs used to treat attention deficit/hyperactivity disorder (ADHD). On March 22, 2006 the FDA Pediatric Advisory Committee decided that the medications do not need "black box" warnings about their risks. The FDA declined to include these black box warnings upon review. According to the Merck Index Methylphenidate had an LD50 of 150mg/kg body mass.
Criticism
Methylphenidate has a role as a frequently-used treatment for ADHD, and as such criticism of methylphenidate is related to the controversy about ADHD, unless it is about alleged or real side effects of the drug. The following points are only about criticism of the drug itself, not about the discussion around ADHD and its diagnosis, the question if it is ethical to give a drug like that to children or general stances against "fixing the mind" with a drug.
[edit] Over prescription
Some have asserted that Methylphenidate is overprescribed, however, the incidence of ADHD is believed to be between three and five percent of the population, while the number of children in America taking Ritalin is estimated at one to two percent.[24] In a small study of four American communities, the incidence of ADHD varied from 1.6% to 9.4%. The study also found that 12.5% of the children meeting the DSM-III-R ADHD criteria for ADHD had been treated with stimulants during the past year.[25]
[edit] Addiction
The question of whether MPH use in children leads to future addictive tendencies has sparked many inquiries and analyses. One study examined the history of a group of adults who had used cocaine at least once, and found that those who as children had been medically diagnosed with hyperactivity and had received methylphenidate treatment for between one and ten years had a percentage of cocaine abuse twice that of either of two control groups: one group of same-age individuals who had not been diagnosed with hyperactivity, and one group of individuals who had also been diagnosed with hyperactivity but had not been treated with stimulants. This research has been described as indicating that "... methylphenidate was still capable of explaining a small but significant proportion of the variance in cocaine use even after approximately 15 years."[26]
However, the increased risk may be due to ADHD itself, because ADHD appears to increase the risk of substance abuse in adulthood [27] [28] [29]. A 2006 study found that those affected by ADHD are naturally at an increased risk of substance abuse and cigarette smoking, but treatment of ADHD decreases that risk.[30] A 2003 project also suggests that boys with ADHD who are treated with stimulants like MPH are actually less likely to abuse drugs (including alcohol) later in life.[31]
[edit] Illicit use
Some people abuse MPH by crushing the tablets and snorting them thus changing the typical theraputic delivery system. The "high" results from the rapid increased rate of dopamine transporter blockade due to quicker absorption into the bloodstream. When abused, the effect of Ritalin is similar to that of cocaine or amphetamine and such abuse can lead to addiction. When taken orally in prescribed doses, MPH has a low addiction liability and rarely produces a "high". Both the United States Drug Enforcement Administration (DEA) and the United Nations International Narcotics Control Board have expressed concern about the ease with which legally prescribed MPH is diverted to the illicit market.[32][33] According to the DEA, "The increased use of this substance [MPH] for the treatment of ADHD has paralleled an increase in its abuse among adolescents and young adults who crush these tablets and snort the powder to get high. Youngsters have little difficulty obtaining methylphenidate from classmates or friends who have been prescribed it."[34]
Volkow et al. (1995) found that the slow clearance of methylphenidate from the brain may discourage the repeated self-administration found in other addictions, reducing the addictive liability of methylphenidate.[35]
Street names for Ritalin include: vernies, diet coke, kiddie cocaine, kiddie coke, vitamin R, R-ball, poor man's cocaine, rids, skittles, R-pop, and smarties.
[edit] Scientology and Anti-Psychiatry criticism of Ritalin
According to a 1990 article by Joel Sappell and Robert W. Welkos in the Los Angeles Times, part of a series of articles about Scientology, "the uproar over Ritalin was triggered almost single-handedly by the Scientology movement."[36] The Citizens Commission on Human Rights, an anti-psychiatry group formed by Scientology in 1969, conducted a major campaign against Ritalin in the 1980s and lobbied Congress for an investigation of Ritalin. Cass Ballenger, a member of the House Education and Labor Committee who met with the Citizens Commission said that "some of the information they provided did not 'add up.'" For example, the article mentions that the Committee claimed a figure of 10-20% of students under age 10 on Ritalin in a particular school district, to which the manager of health services for the district replied, "if they are saying that is the statistic ... they are lying," stating that the percentage of students taking Ritalin or any stimulant for hyperactivity was actually under 1%.[36]
Scientology publications identified the "real target of the campaign" as "the psychiatric profession itself" and claimed the campaign "brought wide acceptance of the fact that (the commission)[sic] and the Scientologists are the ones effectively doing something about [...] psychiatric drugging".[36]
Two of the most famous Ritalin critics Fred Baughman and Peter Breggin would be considered part of the Anti-Psychiatry movement.[37] [38] [39] [40] . They both testified at the Congressional hearing on Ritalin in 2000 and both played a major role in conveying the Anti-Psychiatry message to the public in the popular media during that era and continue to do so. Breggin also played a major role in the failed Ritalin class action lawsuits. While both doctors had associations with Scientology in the past neither belongs to the church. Baughman worked as a medical expert for the CCHR and Breggin had ties to the church but cut off all associations with Scientology in 1974. Baughman, Breggin, and the CCHR share the same ideas and also share content. Breggin and Baughman have written a paper together, while Baughman contributes content to the CCHR. Breggin is also often cited as a reference on CCHR webpages and written material
*excerpts are from http://en.wikipedia.org/wiki/Ritalin*
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