Dextroamphetamine and Amphetamine

The combination of dextroamphetamine and amphetamine, marketed as Adderall, is used for the treatment of Attention Deficit-Hyperactivity Disorder (ADHD) and narcolepsy. The combination of dextroamphetamine/amphetamine is in a class of medications called central nervous system stimulants. Adderall is a combination of racemic (d,l-)amphetamine aspartate monohydrate, dextroamphetamine saccharate, dextroamphetamine sulfate and racemic (d,l-)amphetamine sulfate.

Uses
In the U.S., dextroamphetamine and amphetamine is approved by the Food and Drug Administration FDA for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy in patients three years of age and older. In most European countries, dextroamphetamine and amphetamine is not approved for use in children.

Attention Deficit Hyperactivity Disorder (ADHD)
40 mg per day is the maximum recommended dose. The first dose is taken on wakening; the additional doses are taken every 4-6 hours thereafter.

The starting dose depends on the age:
 * In children from 3-5 years of age, the starting dose is 2.5 mg daily; the daily dosage may be raised in increments of 2.5 mg at weekly intervals thereafter.
 * In children 6 years of age and older, the starting dose is 5 mg once or twice daily; the daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained.

Narcolepsy
The typical dose is a wide range, from 5 mg to 60 mg per day in divided doses. The exact dose depends on the individual.

How Works
The set of amphetamines in dextroamphetamine/amphetamine are drugs that stimulate the central nervous system.

Amphetamines stimulate the central nervous system by blocking the reuptake of the neurotransmitters norepinephrine and dopamine into brain cells, thereby increasing the levels of these neurotransmitters in the space between brain cells.

How the Body Affects
The liver enzyme CYP2D6 metabolizes some dextroamphetamine/amphetamine component amphetamines into 4-hydroxy-amphetamine, but that is all that is known about the metabolism of Adderall at this time.

Approximately 50% of the original dose of amphetamine is excreted in the urine as derivatives of alpha-hydroxy-amphetamine and approximately another 30%-40% of the original dose is recoverable in urine as the parent drug amphetamine itself.

Benefits
One head-to-head study comparing Adderall to Ritalin demonstrated that Adderall is at least as effective as Ritalin in improving the behavior and academic productivity of children with ADHD.

Side Effects
The most common side effects incident with dextroamphetamine/amphetamine use are:


 * Headache or Dizziness
 * Insomnia
 * Dry mouth or unpleasant tastes
 * Diarrhea
 * Constipation
 * Loss of appetite
 * Weight loss
 * Loss of interest in sex, impotence, or difficulty having an orgasm

Complications
Dextroamphetamine/amphetamine may produce allergic reactions to patients with known allergies to amphetamine and dextroamphetamine

Dextroamphetamine/amphetamine is not to be used in patients with hardened arteries, heart disease or congential heart defects, high blood pressure, an overactive thyroid gland, glaucoma, severe anxiety or agitation, or a history of drug or alcohol addiction.

Interactions
The following drugs may interact with dextroamphetamine and amphetamine:
 * Antidepressant substrates of 2D6 such as amitriptyline (Elavil), amoxapine (Ascendin), clomipramine (Anafranil), desipramine (Norpramin), imipramine (Tofranil), or nortriptyline (Pamelor) may interact through competitive inhibition of Cytochrome p450 2D6
 * Use special caution: Antidepressant blockers of 2D6 such as fluoxetine (Prozac), paroxetine (Paxil), will  significantly block 2D6 over time and create accumulation of AMP with significant toxic implications
 * Blood pressure medications
 * Diuretics
 * Antihistamines
 * Acetazolamide (Diamox)
 * Chlorpromazine (Thorazine)
 * Ethosuximide (Zarontin)
 * Guanethidine (Ismelin)
 * Haloperidol (Haldol)
 * Lithium (Eskalith, Lithobid)
 * Methenamine (Hiprex, Mandelamine, Urex)
 * Phenytoin (Dilantin)
 * Phenobarbital (Luminal, Solfoton)
 * Propoxyphene (Darvon, Darvocet)
 * Reserpine
 * Sodium bicarbonate (Alka-Seltzer)

Overdose
Adderall is a Schedule II controlled substance, subject to abuse and addiction. College students at a Northeastern U.S. University reported it as their drug of abuse of choice in 2006.

History
Dextroamphetamine/amphetamine is marketed by Shire Pharmaceuticals since 1996 in the U.S. and is also available in an extended release version called Adderall XR. An alert was released in Canada in 2005 warning against the use of the drug in patients with structural cardiac abnormalities. In 2007, the FDA directed all manufacturers of ADHD drugs to warn users in the U.S. of the risk of sudden death among patients with cardiac abnormalities, and the risk of mania and psychosis among long-term users, including those with no history of psychiatric problems.

Research
Research studies recently concluded involving Strattera include:
 * A comparison between Adderall and Strattera for the treatment of ADHD.
 * The use of Adderall XR in the treatment of ADHD in adolescents (ages 13-17).
 * Comparing dextroamphetamine and amphetamine to methylphenidate for the treatment of memory, thinking and attention problems and depression in children after cancer treatment.
 * Evaluating the possibility of genetic damage caused by treatment with methylphenidate and Adderall.

Clinical Trials
ClinicalTrials.gov: Adderall clinical trials