More Drugs To Treat Hyperactivity

By Alice Park

Back in the 1930s, a physician in Providence, R.I., trying to figure out what caused delinquent behavior in boys stumbled upon a relatively easy way to calm the boys' rowdy tendencies. Giving them stimulants like amphetamines, Dr. Charles Bradley found, actually helped them focus their attention in school, and the first generation of drugs to treat hyperactivity was born.

Since then, the universe of medications to treat attention-deficit/hyperactivity disorder (ADHD) has broadened significantly, ranging from vintage antidepressants known as tricyclics to various drugs for high blood pressure. Both groups seek to restore the balance of brain chemicals that appears to have gone awry in those with ADHD. Doctors generally start with stimulants like Ritalin; if these fail, as happens in about one-fifth of all patients, they move on to other drugs. Here's how each category works:

STIMULANTS

While it seems counterintuitive to give a stimulant to a hyperactive child, those with ADHD actually need to rev up activity in the part of their brain responsible for functions like organization and concentration. Methylphenidates (Ritalin, Concerta, Metadate) and amphetamines (Adderall) will do that by bathing the brain's nerve cells in certain chemicals--dopamine, norepinephrine or serotonin--that promote nerve activity.

Ritalin, the first of the methylphenidates to be approved, works for three to four hours and requires two to three doses a day. The newest generation of drugs in this class does better: Novartis, Ritalin's maker, is waiting to hear whether the FDA will approve its new version, Ritalin LA, which has double the current drug's effective time. Concerta, available since last summer, is effective for 12 hours; Metadate, approved in 1999, lasts about eight hours. A Concerta capsule acts as a minipump, gradually pushing methylphenidate out through tiny, laser-drilled holes in its coating. With Metadate, about one-third of each tablet consists of drug-filled beads that dissolve immediately after swallowing; the other two-thirds contain longer-lived beads that leak their contents over the next four to eight hours.

The required dosage of amphetamines is about half that of methylphenidates, but amphetamines still carry the risk of becoming habit forming. Doctors are hesitant to give them to patients, particularly teens, with a history of substance abuse or addictive behavior. But stimulants are usually well tolerated. The most common side effects are insomnia and loss of appetite.

ANTIDEPRESSANTS

For the 20% of ADHD patients who don't respond to stimulants, doctors prescribe an older class of antidepressants known as tricyclic amines such as Wellbutrin.

These keep levels of serotonin and norepinephrine high but are only about 60% effective in reducing ADHD symptoms. Tricyclics have also been associated with more troubling side effects, including fatal heart attacks in those with a history of heart-rhythm disturbances.

BLOOD-PRESSURE DRUGS

Alpha-adrenergic agents, originally used to treat high blood pressure, have been effective in reducing ADHD symptoms in some children. They work primarily by keeping up levels of norepinephrine and are particularly effective in treating ADHD youngsters who also show signs of impulse or anxiety disorders.

In the coming months, pharmaceutical companies will be releasing even more variations on the Ritalin theme. Novartis has received the FDA's preliminary approval to market another, more refined form of methylphenidate that requires a smaller dosage than the current formulation. Unlike Ritalin LA, however, this drug is not a long-acting medication but addresses the concerns some parents have about giving too much medication to their young children. Eli Lilly, on the other hand, is taking a cue from the blood-pressure medications with a new product called Atomoxetine that boosts norepinephrine. The drug is still being tested, but results so far are promising. The upshot of all these developments will be to make ADHD treatments more customized and ultimately more effective.

--By Alice Park