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.

How Dextroamphetamine and Amphetamine Is Taken

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 Dextroamphetamine and Amphetamine 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 Dextroamphetamine and Amphetamine

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.^[1]

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

Risks

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. ^[2]

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. ^[3] 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. ^[4]
• The use of Adderall XR in the treatment of ADHD in adolescents (ages 13-17). ^[5]
• Comparing dextroamphetamine and amphetamine to methylphenidate for the treatment of memory, thinking and attention problems and depression in children after cancer treatment. ^[6]
• Evaluating the possibility of genetic damage caused by treatment with methylphenidate and Adderall. ^[7]

Clinical Trials

ClinicalTrials.gov: Adderall clinical trials

References

1. ↑ Pelham WE, Aronoff HR, Midlam JK, et al. A comparison of ritalin and adderall: efficacy and time-course in children with attention-deficit/hyperactivity disorder. Pediatrics. 1999 Apr;103(4):e43. Abstract | Full Text
2. ↑ Teter CJ, McCabe SE, LaGrange K, Cranford JA, Boyd CJ. Illicit use of specific prescription stimulants among college students: prevalence, motives, and routes of administration. Pharmacotherapy. 2006 Oct;26(10):1501-10. Abstract
3. ↑ U.S. Food and Drug Administration. Adderall and Adderall XR (amphetamines) Information
4. ↑ ClinicalTrials.gov web site. Analog Classroom Study Comparison of ADDERALL XR With STRATTERA in Children Aged 6-12 With ADHD
5. ↑ ClinicalTrials.gov web site. Safety and Efficacy of ADDERALL XR in the Treatment of Adolescents Aged 13-17 With Attention Deficit Hyperactivity Disorder (ADHD)
6. ↑ ClinicalTrials.gov web site. Dextroamphetamine-Amphetamine Compared With Methylphenidate in Treating Children Who Have Problems With Memory, Attention, Thinking, and Depression Caused By Cancer Treatment
7. ↑ ClinicalTrials.gov web site. Genetic Measurements in Blood Cells of Children Taking Adderall or Methylphenidate

External Links

FDA: Patient Information Sheet