Attention-Deficit Hyperactivity Disorder

Description

Alternative Names

Medications

Psychostimulants to date are the primary drugs used to treat ADHD; they are effective for both children and adults with severe ADHD. These drugs have been intensively studied for decades and there is little evidence for any serious concern with long-term use.

A nonstimulant, atomoxetine (Strattera), is now approved for ADHD in children and the first treatment approved for adult ADHD.

Such agents, however, may not be effective or appropriate in all patients. Some children also suffer from other disorders (e.g., anxiety disorders) that reduce the effectiveness of stimulants. Other children cannot tolerate some of the side effects (tics, insomnia, loss of appetite).

Other agents used for ADHD include certain antidepressants (e.g., tricyclic antidepressants, bupropion) and drugs called alpha agonists (clonidine). A 2002 study reported that children with ADHD are increasingly being treated with combinations of psychostimulants and some of these other agents. 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 emotional disorder, such as bipolar or anxiety disorder.

Determining a Correct Regimen

Physicians 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 physician 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.

Methylphenidate (Ritalin) and Similar Agents

Methylphenidate (Ritalin, Metadate, Concerta) is the most commonly used psychostimulant for ADHD. Its positive benefits for improving ADHD symptoms appear to be due to its actions in increasing dopamine, a neurotransmitter important for motor control. This agent is effective in both children and adults. A similar agent dexmethylphenidate (Focalin) has been approved. It is similar to in methylphenidate in effectiveness and side effects.

Regimen. The older form of Ritalin is short acting, and needs to be taken several times a day, including during school hours. As it wears off, a rebound effect can occur and ADHD symptoms intensify. Longer-acting forms (Concerta, Ritalin LA, Ritalin SR, Metadate) are now available.

Concerta is now the most commonly prescribed agent for ADHD and uses a special pump action that releases the medication gradually into the body and can be effective for 12 hours. Ritalin LA and Metadate also only need to be taken once during the entire school day. (Ritalin SR can still can wear off by early afternoon.) A patch form of methylphenidate (MethylPatch) is awaiting approval. A four-week trial in 2002 reported that it was very effective in improving attention and improving behavior.

A 2003 study of Concerta indicated that depending on the ADHD subtype, children may require different doses. In the study, children with the inattentive type responded to lower doses than those with the combined type.

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.
• Children may lose weight.
• Tics or jerky, disordered movements occur in about 9% of children. Some studies indicate they are not caused by standard doses of Ritalin. In any case, low doses are often effective in controlling impulsivity without causing tics, even in some children who also have mild to moderate Tourette's syndrome.
• Other side effects include irritability, withdrawal, stomach pain, headache, depression, hallucinations, hair loss, and lack of spontaneity.

Of note, taking Ritalin with a high-fat breakfast may delay its effects.

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 very severe, however, if Ritalin is overused and taken with other drugs.)

Long-Term Complications. Many people have taken Ritalin for years without experiencing adverse effects or loss of effectiveness. Few long-term complications have been reported, but the following warrant some caution or additional research:

• Early research had suggested that growth may be retarded during long-term treatment. Recent studies, however, have found little evidence for any significant growth suppression in boys or girls. In addition, a 2003 study found no significant effect on onset of puberty in girls.
• A 2001 study on animals suggested that there may be some long-term effects from methylphenidate that may change brain cell structure or function. Heavy abuse of other stimulants (cocaine, amphetamines) has been associated with worsening in motor skills and attention. However, more research is needed to determine if such changes occur with long-term use of Ritalin. In fact some evidence suggests that Ritalin may help increase white matter (the primary substance that makes up the core of the brain's hemispheres).

Concerns for Abuse. Studies on both animals and humans suggest that 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, in fact, indicated that methylphenidate treatment may even 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 agents. (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 agents illegally. In one study, for instance, 16% of ADHD children reported pressure from their fellow students to sell or give them their medication.

Adderall

Adderall combines four kinds of amphetamine salts. It is inexpensive and can be taken once or twice a day. (Adderall XR is designed to be taken once a day.) Adderall may also be effective for adults. In studies comparing standard forms of Adderall and Ritalin, both drugs are beneficial and the effect on behavior was similar in children. In one major 2002 analysis of comparison studies, parents and physicians reported that Adderall was superior to standard Ritalin, but teachers found no superiority of one agent over the others. Side effects include stomach problems and mood changes, including sadness, anxiety, and irritability. Studies are needed to determine long-term risks.

Other Central Nervous System Stimulants

Pemoline. Pemoline (Cylert) is an effective stimulant in children who do not respond to other drugs. It has shown promise for adults with ADHD but has not been approved for this population. The agent takes longer (sometimes weeks) to produce improvement than the other drugs, but it allows once-daily administration. Of major concern is a risk of liver damage, particularly when taken in combination with other medications or alcohol. Although the risk is small, it can be life-threatening in rare cases. Physicians should monitor liver function every two weeks in children taking the agent. Parents or patients should watch for any symptoms of liver toxicity, including tenderness of the abdomen, yellow skin or eyes, vomiting, weight loss, or malaise. The drug was withdrawn in Canada in 1999.

Dextroamphetamine. Dextroamphetamine (Dexedrine) is similar to Ritalin. Although it is commonly believed that it is both less effective and less safe than Ritalin, there is no evidence of this, and one study reported a slightly better response with dextroamphetamine. Side effects are similar. The arguments against dextroamphetamine mainly rest on widespread abuse of this drug in earlier decades. Some experts believe it may be an useful alternative for people who do not respond to Ritalin.

Atomoxetine

Atomoxetine (Strattera) is the first non-stimulant to be approved for ADHD in children and the first treatment approved for adult ADHD. The drug appears to work by increasing levels of both norepinephrine and dopamine, which are generally lower than normal in ADHD. A number of studies have now reported that atomoxetine is effective and safe. It is proving to reduce ADHD symptoms, improve well being, and even reduce problem behaviors. It appears to be as effective as methylphenidate and is well tolerated. The most common side effect to date is decreased appetite. Long-term effects, such as any impact on growth, are still unknown.

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 unique antidepressants, sometimes referred to as designer antidepressants. Such agents affect one or more neurotransmitters that are not targeted by older antidepressants. These agents 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.

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 in fact they may increase the risk for impulsive behavior. The effects of long-term use of SSRIs in young people are not clear. There have been case reports of myoclonus (uncontrolled muscle jerks) with long-term use. In addition, there is some concern that SSRIs may limit growth in children. Although there have been reports of a greater risk for suicide in young people taking Paxil, the evidence supporting such reports is weak. Intensive research is underway to determine if SSRIs pose a risk for suicide in anyone.

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's 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 agents 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 agent 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

Anticholinesterases. Drugs known as central anticholinesterases, including tacrine (Cognex) and donepezil (Aricept), are used to treat symptoms of Alzheimer's disease. Currently, they are also being investigated for ADHD. Some early studies suggest that such an agent may be effective in the same way as psychostimulants and may also have additional benefits, including improving executive functions, such as organizational capacity. All these drugs have gastrointestinal side effects, including nausea. In high doses, they can also cause liver damage.

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. Note: Selegiline can cause hypertension if combined with agents that increase serotonin levels--such agents include nearly every major antidepressant.

Modafinil. Modafinil promotes wakefulness and is used to treat patients with narcolepsy. It is being investigated for adults and children with ADHD, but studies have been mixed on its benefits.