Adderall

Adderall XR 15 mg capsule

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

History

Brand name Adderall was introduced in 1996 in the form of a multi-dose, instant-release tablet that came from the original formula used in the weight management drug Obetrol. It has since become available in a generic formulation of "mixed amphetamine salts". The active ingredients of Adderall include a combination of dextroamphetamine and racemic d/l-amphetamine salts. Shire Pharmaceuticals later introduced an extended-release preparation of these ingredients in a variety of dosages, under the brand name "Adderall XR" (extended release), on which Shire retains exclusive patent rights until 2009.

Chemistry

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

• 1/4 dextroamphetamine saccharate
• 1/4 dextroamphetamine sulfate
• 1/4 (racemic dextro/laevo-amphetamine) aspartate monohydrate
• 1/4 (racemic dextro/laevo-amphetamine) sulfate

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

The average elimination half-life in adults for dextroamphetamine 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 (d,l)-amphetamine excretion and absorption. Co-administration of acidic substances (e.g. citric acid) causes an accelerated excretion of (d,l)-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 CNS stimulants of the same class and preparation (see amphetamine for details).

Dosing and administration

Adderall is marketed as either an immediate-release tablet, Adderall, or an extended-release capsule, Adderall XR ("Extended Release"). Doses for both Adderall XR and Adderall are 5, 10, 15, 20 30 milligram strengths with Adderall having two extra ones, 7.5 and 12.5 milligrams and Adderall XR having a 25 milligram dose.

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 regular Adderall, which reaches maximum plasma concentration within three hours. As a result of its high bioavailability, Adderall XR's effectiveness is not altered by food absorption in the gastrointestinal tract. However, mean plasma concentration is prolonged by 2.5 hours (using a standard high-fat meal as the control). Medications that alter urinary pH will cause variations in amount and method of excretion and usage should be monitored when taken concurrently with Adderall.

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

Generic equivalents/alternatives

The closest generic equivalent to Adderall is dextroamphetamine sulfate also known as Dexadrine and available in a sustained release form called Dexedrine ER. It should be noted that Adderal uses "mixed amphetamine salts" and Dexadrine is a single salt therefore Dexedrine ER is not a strict generic equivalent for Adderall XR, though it 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 Adderal is still protected under patent in the United States. Until this patent expires, generic versions of Adderal XR will not become available.

Vyvanse is a derivative of Dexedrine, yet it behaves differently in the body (see Dextroamphetamine at "Formulations"). The manufacturer has added extra ingredients (in the case of Adderall) or created a prodrug (a precursor) of dextroamphetamine (in the case of Vyvanse) in order to patent allegedly "improved" products that are similar to Dexedrine yet cannot be produced generically for the time being.

Mechanism of action

Main article: 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. 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.

Side effects

In children

• Decreased appetite
• Difficulty falling asleep
• Stomach ache
• Emotional lability
• Dry mouth

In adults

• Dry mouth
• Loss of appetite
• Difficulty falling asleep
• Weight loss
• Symptoms of depression/anxiety

Unspecified ages

• Abdominal pain
• Angina (sudden acute pain)
• Anorexia
• Asthenia (unusual weakness or tiredness)
• Blood pressure and pulse changes
• Blurred vision
• Depression
• Dizziness
• Drowsiness
• Fever
• Headaches
• Heart palpitations
• Hypersensitivity
• Impotence
• Insomnia
• Involuntary tics and twitching
• Liver problems
• Loss of appetite
• Mood disorders (including aggression, irritability, and violent behavior)
• Moodiness
• Nausea
• Nervousness
• Psychosis or toxic psychosis
• Restlessness
• Seizures
• Stomach pain
• Stunted growth
• Tachycardia (rapid heartbeat)
• Vomiting
• Weight loss

From overdose

These symptoms require immediate medical assistance:

• Symptoms of tourettism
• Aggression
• Symptoms of depression
• Seizures or abnormal EEGs
• High blood pressure
• Tachycardia
• Swelling of hands/feet/ankles (for example, numbing of the fingertips)
• Delusions
• Hallucinations
• Sweating
• Vomiting
• Dehydration
• Unexplained 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 manifest itself as psychosis, often indistinguishable from schizophrenia.

Contraindications, interactions, and precautions

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

• SSRIs (selective serotonin reuptake inhibitors, 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 inhibitors, 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 inhibitors) — 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 inhibitors, 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 (tricyclic antidepressants, e.g., Imipramine, Tofranil, Janamine, etc.) — See SNRIs and SSRIs. Possible potentiation of 5htp (serotonin), dopamine and norepinephrine related drug effects. Use only when indicated.

Performance-enhancing use

Due to side effects including appetite suppression and weight loss, Adderall has also been used as an off-label drug for obesity.

Professional poker player Paul Phillips claimed that the use of Adderall and other medications prescribed to him for ADHD treatment made him a much better player and helped him earn more than $2.3 million in poker. The drugs improved his concentration during high-stakes tournaments, he said, allowing him to better track all the action at his table.

Adderall is also reportedly widely used as a "study drug" at most major American universities; students may sell or trade the drug for other prescription drugs like oxycodone, or other illicit drugs. Adderall is reported to help focus energy and concentration to a much higher level than normal; 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.

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. 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. 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.

Further reading

• Hanna, Mohab "Making the Connection: A Parent's Guide to Medication in ADHD" Ladner-Drysdale 2006