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Consumer Health

Ped Med: ADHD drug paradoxes
By Lidia Wasowicz Apr 19, 2006, 10:48 GMT
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SAN FRANCISCO, CA, United States (UPI) -- Even after decades of discussion and debate, scientists have yet to unravel many of the paradoxical puzzles presented by pharmaceuticals used to treat attention-deficit/hyperactivity disorder.

Why, many wonder, do stimulants settle down children who already appear to be overstimulated? And why do prone-to-abuse Schedule II controlled substances not only not get hyperactive children hooked but also apparently lessen their risk of future addictions, as most studies suggest and most mainstream practitioners contend?

Researchers say the compounds appear to help suppress certain behaviors by altering one or more of three chemical messengers in the brain, the neurotransmitters dopamine, norepinephrine and serotonin, which the prevailing, though far from proven, theory implicates in ADHD comportment. In a counterintuitive twist, the chemical change somehow leads to improved self-control -- provided the dose is right, investigators say.

Too much drug, and the hyperactivity revs up into even higher gear, while attention span sputters.

In one of the first studies to probe the mystery in humans, government researchers observed in lab experiments how the stimulant Ritalin boosts levels of dopamine, the brain chemical associated with feelings of reward and pleasure, stimulating attention and motivational circuits that fire up the ability to focus and complete tasks.

These circuits do not work at full capacity in those with ADHD, who stray off focus with the slightest distraction, the controversial theory goes. By normalizing the chemical levels, Ritalin should get them back on the attention track, scientists speculate.

The researchers also gleaned a clue as to why users with the disorder do not appear to get 'high' from the drug, a kissing-cousin of cocaine, chemically speaking.

In contrast to the immediacy of an injected drug shooting its way to the brain, in pill form, it takes a stimulant like Ritalin at least an hour to raise the mood-enhancing dopamine levels in the brain, apparently too long a lag to present much of an addiction threat, they conjecture.

Recent research by Dr. George Bartzokis of the University of California, Los Angeles, also seems to point to the distribution and dose of the drug reaching the brain as key factors in its effects. His experiments indicate the greater the chemical`s speed and substance, the more severe the toxic shock to the system.

'The toxicity is often related to rate of delivery to the brain and amount,' explained Bartzokis, a professor of neurology. 'For example, a glass of wine drank over dinner is likely good for you. Drinking an entire bottle of wine in one minute on an empty stomach is an entirely different and likely toxic proposition.'

His research shows alcohol and other substances of abuse can poison the production process of a critical fatty shield, called myelin, that protects cells from damage, bamboozling treatment efforts and aggravating co-existing psychiatric disorders.

Could these troublemaking substances include the very stimulants used to treat conditions like ADHD but which studies show are rampantly abused by those not prescribed the drugs? Could this effect also occur in children misdiagnosed with ADHD and erroneously treated with the drugs?

'It`s a very interesting and complex question,' mused Bartzokis, a pioneer in the neuroscience of brain development and degeneration.

'The brain responds differently in childhood than in adulthood,' he noted. 'In childhood, for example, there is a greater effort to myelinate (coat with the fatty sheath) new circuits.'

'There have been some studies examining the impact of these medications in children, and the overall result is that they are beneficial or have no untoward effects in children with the diagnosis,' he continued. 'There was a recent (laboratory study) that suggests increasing dopamine stimulation (as amphetamines used to treat ADHD do) may actually protect the cells that make myelin.'

The effects of the stimulants in children not diagnosed with ADHD have not been studied, and will likely remain a mystery. Such research could not be conducted, for ethical reasons, except in cases of substance abuse, scientists say. Studies of abusers show cognitive decline, but most of those have been limited to adult participants, they say.

Interruptions in the formation of the myelin shield -- be it by misused substances or other disrupters -- may contribute to or worsen disorders such as autism, ADHD and schizophrenia, the research suggests.

If the insulation of the brain`s 'stop' circuits is incomplete, these brakes cannot act to forestall any runaway effect of the 'go' wiring, which starts functioning earlier in development, the investigators postulate. Hence, if the wrapping of the inhibitory wiring in protective myelin stalls, the mechanisms are not on line to restrain the high-risk behaviors prevalent in adolescence and early adulthood, they propose.

Might the finding explain why the behavioral symptoms of ADHD often resolve themselves over time, with or without treatment -- as these circuits start kicking in?

'Yes, that may be an explanation for that phenomenon,' Bartzokis speculated. 'The advantage of treatment (if indicated) is that it is absolutely necessary for the more severe cases.'

For the less serious cases, the treatment options are less straightforward and far more controversial.

'There is no psychoactive drug that does not injure the brain short- and long-term and impair perception, learning and adaptation. So a drug abolishes ADHD behaviors, conduct disorder behaviors, oppositional defiant disorder behaviors. They do nothing but abolish,' neurologist Dr. Fred Baughman, a long-time critic of the use of psychiatric drugs in children, wrote in an April 18 infomail sent to his Website subscribers. 'When is the child to learn to control these behaviors with the normal brain God gave him?'

The answers aren`t easy, specialists say.

'It is a very complex problem,' Bartzokis said. 'For kids with mild ADHD that are sent to school, it may be quite traumatic to try to function in the increasingly structured environment as they move up in grades. It is difficult to find optimal solutions, and the highest levels of expertise and resources are needed.'

Next: Playing hit and miss with treatments..

UPI Consumer Health welcomes comments on this column. E-mail Lidia Wasowicz at lwasowicz@upi.com

Copyright 2006 by United Press International