Medications:

Several types of medication are available to treat ADHD.

Psychostimulants: Methylphenidate (Ritalin) and Similar Drugs

Psychostimulants are the primary drugs used to treat ADHD. Although these drugs stimulate the central nervous system, they have a calming effect on people with ADHD.

These drugs include:

• Methylphenidate (Ritalin, Concerta, Metadate, Daytrana)
• Dexmethylphenidate (Focalin)
• Amphetamine-Dextroamphetamine (Adderall)
• Dextroamphetamine (Dexedrine, Dextrostat)
• Lisdexamfetamine (Vyvanse)

Pemoline (Cylert), another stimulant drug, was withdrawn from the U.S. market in 2005 after several reports of liver failure.

Methylphenidate and Dexmethylphenidate. Methylphenidate drugs (Ritalin, Metadate, Concerta, Daytrana) are the most commonly used psychostimulants for treating ADHD in both children and adults. Dexmethylphenidate (Focalin) is a similar drug. These drugs increase dopamine, a neurotransmitter important for cognitive functions such as attention and focus.

With the exception of Daytrana, all of these drugs are pills taken by mouth. Daytrana, approved in 2006, is the first skin patch drug for ADHD. A patch is applied to the hip each day and delivers a 9-hour dose of methylphenidate.

These drugs are available in short-acting and long-acting dosage forms. The short-acting forms need to be taken several times a day, including during school hours. As the drug wears off, a rebound effect can occur, and ADHD symptoms can intensify. For this reason, the long-acting dosage forms have become popular.

Amphetamine, Dextroamphetamine, and Lisdexamfetamine. Amphetamine-dextroamphetamine (Adderall), dextroamphetamine (Dexedrine, Dextrostat), and lisdexamfetamine (Vyvanse) work by blocking the reabsorption of the brain chemicals dopamine and norepinephrine. Side effects can include stomach problems and mood changes, including sadness, anxiety, and irritability.

Risks of Stimulants

Psychostimulant medications are associated with some significant risks. All ADHD stimulant drugs carry warnings that they should not be used by patients with structural heart problems or pre-existing heart conditions (high blood pressure, heart failure, heart rhythm disturbances, or congenital heart disease). These drugs have been associated with sudden death in children with heart problems. They have also been associated with sudden death, stroke, and heart attack in adults with a history of heart disease.

The American Heart Association (AHA) currently recommends cardiac testing prior to prescribing stimulant drugs for children. The AHA recommends that doctors:

• Get a complete patient and family history
• Conduct a physical exam to check for heart problems, including heart murmurs and high blood pressure
• Arrange a consultation with a pediatric cardiologist if necessary
• Consider ordering an electrocardiogram (ECG) to check for heart abnormalities (in contrast, the American Academy of Pediatrics does not recommend routine use of ECGs before starting stimulant therapy)
• Monitor patients on stimulant drugs for emergence of cardiac symptoms

The AHA notes that stimulant drugs remain a reasonable option for children with stable heart disease or those who are currently receiving care from a pediatric cardiologist.

Stimulant drugs may also:

• Worsen behavior and thought disturbance in patients with a pre-existing psychotic disorder. These drugs may also slightly increase the risk for auditory hallucinations, paranoia, and manic behavior even in patients who do not have a history of psychiatric problems.
• Cause a mixed or manic episode in patients who have both ADHD and bipolar disorder.
• Increase aggressive behavior or hostility. Patients beginning stimulant drug treatment should be monitored for worsening of these behaviors.
• Slow growth and weight gain in children. Children who take stimulant drugs should have their growth monitored. If they do not gain height or weight at a normal rate, they may need to stop taking the drug.

The FDA has directed manufacturers of ADHD medications to warn all patients taking these medicines of their potential cardiovascular and psychiatric risks.

Side Effects. All stimulants have a number of side effects:

• The most common side effects of any stimulant are nervousness and sleeplessness, although some parents have reported improved sleep patterns in their children after taking stimulants.
• Tics or jerky, disordered movements occur in about 9% of children.
• Other side effects include irritability, stomach pain, headache, depression, hair loss, and lack of spontaneity.

Symptoms of Overdose. Symptoms of overdose include changes in heart rhythm and rate, hypertension, confusion, breathing difficulties, sweating, vomiting, and muscle twitches. If they occur, parents should call the doctor immediately. Even among young people who abuse Ritalin, however, less than 1% experience severe side effects (rapid heart rate, hypertension), and outcomes are generally good. Side effects may be very severe, however, if Ritalin is overused and taken with other drugs.

Concerns for Abuse. Studies on both animals and humans suggest that Ritalin lacks the properties that create addiction, particularly in doses used for treating ADHD. Although methylphenidates have properties similar to amphetamines, their drug levels rise very slowly in the brain at the oral doses given for ADHD. This slow rise prevents a so-called "high" and subsequent addiction to the drug. Some stimulant drugs, such as lisdexamfetamine, may pose a lower risk for abuse than others.

The primary danger for drug abuse from stimulants appears to occur in young people without ADHD who purchase these drugs illegally. In one study, 16% of children with ADHD reported pressure from their fellow students to sell or give them their medication. While people ages 18 - 25 are more likely to use ADHD drugs for non-medical uses, children ages 12 - 17 are more likely to suffer adverse effects from medication misuse and to require treatment at an emergency room. If a child abuses another drug (alcohol, prescription medication) along with the ADHD medication, the chance for serious side effects is even greater.

Non-Stimulant: Atomoxetine

Atomoxetine (Strattera) was the first non-stimulant approved for ADHD in children and the first treatment approved for adult ADHD. The drug works by increasing levels of both norepinephrine and dopamine, which are generally lower than normal in ADHD. The most common side effect is decreased appetite. A few cases of atomoxetine-associated liver injury have been reported, and the FDA has warned doctors that the drug should be discontinued at the first signs of jaundice (yellowing of skin and eyes) and liver problems. Long-term effects, such as any impact on growth, are still unknown. Atomoxetine may cause suicidal thinking in children and adolescents, especially during the first few months of treatment. Parents should monitor children taking atomoxetine for any changes in mood or behavior, and immediately contact their doctor if changes occur.

Antidepressants

Antidepressants are not FDA-approved for ADHD treatment, but may be helpful in certain circumstances. Because antidepressants appear to work about as well as behavioral therapy, doctors recommend that patients first try psychotherapy before using antidepressants.

Bupropion (Wellbutrin) and tricyclics are the types of antidepressants used for ADHD. Bupropion affects the reuptake of the serotonin, norepinephrine, and dopamine neurotransmitters. Side effects include restlessness, agitation, sleeplessness, headache, and stomach problems. Bupropion should not be used by patients who have a seizure disorder.

Tricyclics are an older type of antidepressant that can be beneficial but have many side effects. Imipramine (Tofranil) and nortriptyline (Pamelor, Aventil) are the tricyclics most commonly prescribed for ADHD. A third tricyclic, desipramine (Norpramin) should only be used if patients are not helped by other tricyclics. (Desipramine has caused sudden death in some children and adolescents.)

Tricyclic antidepressants can cause disturbances in heart rhythm. Children should have an electrocardiogram when they first begin to take this drug, and after any dose increase.

[For more information, see In-Depth Report #8: Depression ].

Alpha-2 Agonists (Clonidine)

Alpha-2 agonists stimulate the neurotransmitter norepinephrine, which appears to be important for concentration. They include clonidine (Catapres) and guanfacine (Tenex). They are used for Tourette syndrome and may be beneficial when other drugs have failed for ADHD children with tics or those whose primary symptoms are severe impulsivity and aggression. These drugs are mainly prescribed in combination with a stimulant.

These drugs have a number of side effects. Sedation is the most common. A clonidine skin patch, which gradually releases the medication, helps reduce the sedative effect. Because clonidine slows the heart down, it can have adverse effects in some children. Going off too quickly or missing doses can cause rapid heartbeats and other symptoms that may lead to severe problems. Doctors strongly recommend that no child be given this medication without a preliminary examination for heart problems, and no child with existing heart, kidney, or circulatory problems should take it.