Medication

Several medications 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)

Pemoline (Cylert), another stimulant drug, was withdrawn from the U.S. market in 2005 after several reports of liver failure.

As of 2006, all ADHD stimulant medications carry warnings that they should not be used by patients with structural heart problems or pre-existing heart conditions (high blood pressure, heart failure, or heart rhythm disturbances). 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. In February 2007, the Food and Drug Administration directed manufacturers of ADHD medications to warn all patients taking these medicines of potential cardiovascular and psychiatric risks.

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 and Dextroamphetamine. Amphetamine-dextroamphetamine (Adderall) and dextroamphetamine (Dexedrine, Dextrostat) 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.

In 2006, the manufacturer of Dexedrine updated its prescription label. In addition to strengthening the warning that Dexedrine may be fatal for children and adolescents with heart problems, the updated label also warns that stimulant drugs:

• May worsen behavior and thought disturbance in patients with a pre-existing psychotic disorder.
• May cause a mixed or manic episode in patients who have both ADHD and bipolar disorder.
• May be associated with increased aggressive behavior or hostility. Patients beginning stimulant drug treatment should be monitored for worsening of these behaviors.
• May cause slowing of growth 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.

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.
• These drugs may interfere with height and weight gain.
• Tics or jerky, disordered movements occur in about 9% of children.
• Other side effects include irritability, withdrawal, stomach pain, headache, depression, hallucinations, 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. A 2006 study reported that over 3,000 people are treated in hospital emergency rooms due to side effects from ADHD drugs. Sixty-one percent of these visits involved accidental ingestion or overdose.

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.

A major analysis in 2003 indicated that methylphenidate treatment may protect young people with ADHD from abusing alcohol or other drugs. In such cases, methylphenidates may reduce the need to self-medicate ADHD symptoms using nicotine, alcohol, or illegal drugs. (Ritalin does not protect against substance abuse in young people with ADHD and conduct disorder, however.) Dependence has not been reported in children who have taken this drug for long periods in appropriate dosages. It should be noted, however, that crushing the pills and inhaling them nasally can provide a euphoric state. The primary danger for drug abuse from stimulants appears to occur in non-ADHD young people who purchase these drugs illegally. In one study, for instance, 16% of children with ADHD reported pressure from their fellow students to sell or give them their medication. A 2006 study indicated that 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 or liver problems. Long-term effects, such as any impact on growth, are still unknown. In 2005, the FDA warned that 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

Specific antidepressants are proving to be helpful under certain conditions, and some may be reasonable alternatives to psychostimulants for some people with ADHD.

Designer Antidepressants. Bupropion (Wellbutrin), reboxetine (Edronax), and venlafaxine (Effexor) are sometimes referred to as designer antidepressants. They affect one or more neurotransmitters that are not targeted by older antidepressants. These drugs may be particularly helpful for treating patients with ADHD and accompanying disorders, including depression or conduct disorder. Most studies to date have focused on bupropion and have reported good results in both children and adults. Patients should be aware that venlafaxine carries a high risk of fatal overdose, particularly if it is taken in combination with alcohol or other drugs.

Tricyclics. Antidepressants known as tricyclics, which include desipramine (Norpramin, Pertofrane), or imipramine (Janimine, Tofranil), have been prescribed for children who do not respond to stimulants or who have accompanying problems, such as tics, anxiety, or depression. Desipramine appears to have the best results of the tricyclics and may even help control impulsivity. Tricyclics can have distressing side effects however, including dry mouth, sleepiness, and constipation. They have mild effects on blood pressure and heart rate, but such effects do not appear to be harmful in people without existing heart disease. Reports of sudden death of a few children taking tricyclics, however, have caused alarm, although these occurrences are extremely rare and the role tricyclics may have played is not clear. Reports of delirium and increased heart rate have occurred in adolescents who take tricyclics and smoke marijuana. Careful monitoring is important.

SSRIs. The antidepressant drugs known as selective serotonin reuptake inhibitors (SSRIs) -- which include fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa), and paroxetine (Paxil) -- are sometimes recommended for treating depression in ADHD patients with both conditions. They have little effect on ADHD and may increase the risk for impulsive behavior. The effects of long-term use of SSRIs in young people are not clear. Some SSRIs, such as paroxetine (Paxil), have been linked to increased risk for suicidal thoughts and behavior in children and teenagers. Fluoxetine (Prozac) is currently the only SSRI approved for treating depression in children and adolescents.

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 have a number of side effects. (Guanfacine may have fewer than clonidine.) 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.

Studies in general report that the drug is safe, including in combination with stimulants. Of concern, however, were reports of five deaths in children taking clonidine with other medications. Experts 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.

Other Medications Investigated for ADHD

Selegiline. Selegiline (Eldepryl, Movergan, Zelepar), also known as deprenyl, metabolizes into compounds found in methamphetamine and blocks monoamine oxidase B (MAO-B), an enzyme that degrades dopamine. A well-conducted study in 2003 suggested that it may be as effective as Ritalin with fewer size effects. Selegiline can cause hypertension if combined with drugs that increase serotonin levels -- such drugs include nearly every major antidepressant.

Modafinil. Modafinil (Provigil) promotes wakefulness and is used to treat patients with narcolepsy. It is being investigated for adults and children with ADHD, and is showing promising results.

Determining a Correct Regimen

Doctors still have a difficult time predicting which medications will produce beneficial results, so treatment is individualized and performed on a trial and error basis, which requires close observation and cooperation between all participants. In developing an effective medication plan, the following steps may be helpful:

• Before any drug is administered, a child should be given a thorough examination for any medical problems to be sure there are no medical conditions that interfere with the medication.
• Both the doctor and the parents should be very clear about the specific behaviors they hope the medication will target.
• The goal is to use the lowest possible dosage that produces improved behavior.
• If an initial regimen doesn't work, changing the dosage, adding another drug, or changing to a different medication often brings improvement. Some experts recommend trying a second psychostimulant if a first one fails. If the child still doesn't respond, antidepressants or other second-line drugs may be beneficial.
• Frequent follow-up visits should be scheduled to assess the response and to detect possible side effects.

Medications in Older Children. As children enter adolescence, the social stigma associated with ADHD often makes them reluctant to continue drug treatment. If the drug has proven to be effective, it is very important to keep the young person on the regimen during this critical period.

Medications for Adults. One report suggested that two-thirds of adults with ADHD may also be successfully treated with stimulants and psychotherapy. Certain antidepressants may also be effective treatments in adults.

Combination Therapy. A 2002 study reported that children with ADHD are increasingly being treated with a combinations of psychostimulants and certain antidepressants (such as tricyclic antidepressants and bupropion), and psychostimulants plus clonidine. Experts warn that there is little evidence that such combinations add any benefits, and their long-term safety is unknown. Nevertheless, combinations may be warranted in certain severe cases, such as in children who are also suffering from an accompanying psychiatric disorder, such as bipolar or anxiety disorder.