SAN FRANCISCO, April 21 (UPI) -- Treating attention-deficit/hyperactivity disorder with medication can take some fiddling.
Among the difficulties is the high rate -- as many as one in three -- of children who either have no response or an intolerable one to the prescribed drug.
If a medicine fails to start subduing symptoms within a week, the doctor may begin tinkering with the dosage. If the behaviors persist, the child may be switched to a different medication. There may be an encore of this largely hit-and-miss performance if the drug effects begin to wane over time.
"Although it is true that the majority of individuals with ADHD initially respond positively to stimulants, long-term effectiveness is much more modest," noted the authors of a study looking into the viability of someday using testable genetic differences to foretell a drug's effectiveness in a particular child.
"Being able to predict which individuals are likely to respond positively or which individuals do not tolerate stimulants would alter the trial-and-error approach to stimulant treatment of ADHD," the researchers said.
Until such a crystal ball is created, doctors subscribing to pharmaceutical solutions must play medicinal musical chairs. If on the second or third go-around, no first-line stimulant -- methylphenidate or amphetamine -- has secured a place as a tried-and-true treatment, it usually yields to another class of contenders.
These may include less powerful stimulants such as benzophetamine and modafinil (trade name Provigil), antidepressants, such as the tricyclics Imipramine or Desipramine or bupropion (Wellbutrin), anti-hypertension medications like guanfacine (Tenex) or clonidine (Catapres, Clorpres or Combipres) or, less frequently, a combination of the medicines.
Most of these are controversial alternatives which critics decry as overly fraught with risks.
For example, in an analysis of ADHD drug treatments, Consumers Union noted that even though some doctors may prescribe it as such, the anti-narcolepsy drug modafinil lacks FDA sanction and, in the consumer advocates' eyes, sufficient scientific support as a remedy for ADHD.
Last month, on a non-binding 12-1 vote, a panel of U.S. medical advisers agreed, recommending a thumbs-down for now to the approval of the drug, renamed Sparlon, as an ADHD treatment for youngsters ages 6 to 17.
The experts agreed the medicine was effective but expressed concerns about its safety, among other issues. These were raised in reports of a number of possible side effects from the medication, including a rare but fatal skin disorder called Stevens Johnson syndrome and increased risk of suicidal thoughts and behaviors, aggression or psychosis.
The Food and Drug Administration advisory panel suggested the drug's maker, Cephalon Inc., further investigate the potential health risks in a month-long study of 3,000 ADHD youngsters.
In its own treatment review, the American Pediatric Association committee recommends use of tricyclics -- which carry a warning of, among other side effects, an increased risk of suicidal thoughts in adolescents -- only when children have shown no response to at least two stimulant drugs or have experienced intolerable side effects.
In 2003, amidst great hoopla, another option became available in a market stimulants had monopolized for decades: Eli Lilly and Co.'s Strattera, touted as the first new type of drug approved for children with ADHD in 30 years.
Boasting a different mechanism of action and a virtually non-existent potential for abuse, atomoxetine, to use Strattera's generic name, is classified as neither a stimulant nor a controlled substance.
That means unlike stimulants -- which under strict Drug Enforcement Administration regulations require a new, hand-delivered prescription each month -- atomoxetine can be called in on the phone, ordered in large quantities, written as refills and even handed out as samples.
Some critics, however, take issue with the drug's categorization as a non-stimulant.
"Atomoxetine meets all three of the World Health Organization's criteria of psychostimulant: 1) chemically, it is derived from a known stimulant -- phenylpropanolamine; 2) pharmacologically, it modulates catecholamine transmission in the central and peripheral nervous systems - for example, it increases heart rate and blood pressure, and 3) behaviorally, it increases focus in ADHD, enhances wakefulness in narcolepsy and suppresses appetite in obesity," said Dr. Grace Jackson, a psychiatrist, lecturer and author of "Rethinking Psychiatric Drugs: A Guide for Informed Consent," (Author House, 2005).
Scientists aren't quite sure about the exact mechanisms involved in how the drugs produce their effects. Generally speaking, stimulants like Ritalin rev up brain cells involved in paying attention and focusing.
Rather than arousing brain chemicals, Strattera works by selectively blocking their re-absorption, and specifically that of the neurotransmitter norepinephrine, which plays a part in regulating impulse control, organization and attention. Here, too, the precise details of the action remain under investigation.
The heavily advertised drug made a huge initial splash before sales started to sink under the weight of a newly ordered "black-box" warning, the strongest kind, of an increased risk of suicidal thoughts in some adolescent users.
In addition, Strattera -- which underwent nine weeks of testing for effectiveness and one year for safety in children 6 and older -- was linked to severe liver damage in rare cases.
The FDA also warns Strattera users of the potential for weight loss and perhaps slowed growth in children taking the medication for prolonged periods, as well as such less serious effects as upset stomach, decreased appetite, nausea or vomiting, dizziness, tiredness and mood swings. Some children and adolescents also may experience numbness and tingling usually in the hands and feet and slightly raised heart rate and blood pressure. These effects usually do not last, but researchers do not yet know what impact, if any, they may have on long-term health.
In general, the advocacy group Consumers Union, which conducted a comprehensive review of ADHD drug treatments, cautions against the American proclivity to judge newer as better.
"Studies consistently show that many older medicines are as good as, and in some cases better than, newer medicines," the report noted. "Newer drugs have not yet met the test of time, and unexpected problems can and do crop up once they hit the market."
Next: Knowing when to fold them and when to hold them in the ADHD treatment gamble.
(Editors' Note: This series on ADHD is based on a review of hundreds of reports and a survey of more than 200 specialists.)
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