Placebo May Augment Effects of ADHD Meds

Small Study Suggests Low-Dose Medications Helpful When Paired With Placebo

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May 5, 2003 -- A new study shows some kids with ADHD may do just as well with half as much medicine when a placebo is added to their treatment -- and may have fewer side effects. Is it an effect of "body conditioning" or a sign that behavioral treatments may allow kids to take less medication? Specialists tell WebMD that we may not have the answer just yet -- but it's hopefully on the way.

"Many children with ADHD experience serious side effects, prompting their parents to stop the medications," says study researcher James Bodfish, PhD, professor of psychiatry at the University of North Carolina. "The question is, 'Is there a way to produce similar effects of the medication with fewer side effects?'"

Since logic says that lowering doses may reduce the risk of these side effects, it would be a treatment boon if these lower doses of ADHD medications could still adequately treat the symptoms. With placebo conditioning, Bodfish's theory goes, the body could be "trained" to react to the "dummy pill" in the same way that it would to the usual drug at a lower dose.

Researchers say that in their study, about 40% of children responded well to half their regular ADHD medication dose -- managing their symptoms with fewer side effects -- but only when given in conjunction with a placebo. Children who took lower doses without the placebo had fewer side effects, but didn't manage their conditions as effectively. They were given their regular and lower doses, with and without placebo, in alternating weeks over the three-month study.

These findings, which involved 26 ADHD children between ages 7 and 15, were presented Sunday at the annual meeting of the Pediatric Academic Societies, whose members largely include university-based medical researchers.

While stimulant drugs such as Ritalin are effective in treating symptoms in many ADHD children, they can cause side effects such as sleep problems, jitters, weight loss, and stomach upset. And nearly half of those with some types of ADHD don't respond to the medications at all. Some experts are also concerned with their long-term use.


"There is a large body of evidence on the placebo effect, and it's possible that pairing a placebo drug with their active [ADHD] medication has the potential to elicit a similar physiological benefit," Bodfish tells WebMD. "If you repeatedly present two things together, the body conditions itself to respond a certain way. If someone rings a dinner bell every time they feed you dinner, after time, your body would respond to the bell sound alone as if you're seeing, smelling, and even tasting the food."

Psych 101 grads may remember this "conditioning" response from Pavlov's famous dog, who was conditioned to salivate upon hearing a bell.

While Bodfish's study was small and lasted only three months -- too short to study long-term effects -- he is currently testing this theory in a larger trial involving 150 ADHD children for longer period, courtesy of a National Institutes of Health grant.

The pill initially used with a half-dose of regular active medication was made to look visually distinctive, and the patients and their parents were fully told of the study's intention. "We explained that previous studies have shown that you can condition medication effects with a placebo, and there is a possibly they could get similar effects with less side effects using this placebo pill with a lower dose of their regular drug," Bodfish says.

This conditioning response may be behind the so-called "placebo effect," the reason why many participants in medical studies respond favorably when given the "dummy" pills, which primarily consist of sugar.

However, the study was too small and short-term to draw convincing conclusions, say two experts not involved in the research.

"This is certainly an interesting finding, and they present a great theory that is consistent with other studies," says neurologist Thomas Megerian, MD, PhD, ADHD specialist at Children's Hospital of Boston. "We see around a 30% response rate to placebo in depression and many other psychiatric conditions. But at this point, these researchers are hinting at an effect but the results aren't there."

Megerian says that while the study results suggest improvement with placebo, the results were not statistically significant. "This is what we call 'a trend toward significance,' but we're not there yet," he tells WebMD. "This is probably why the NIH said, 'do this on a larger number of people.'"


In other words, while more children responded well with the placebo, some children -- though not as many -- also responded well to a lower dose of medication without the sugar pill. "It's hard to tell in this study what these kids needed in terms of medication," Megerian says. "Maybe all the kids needed to be on half the dose of medication, since no information was given on how severely affected they were. Were these borderline cases of ADHD, children who didn't need much of a nudge to get them across to responding favorably? It's good that they're doing more research, because more is needed."

Another ADHD specialist tells WebMD says that because the children studied received alternating doses for week-long periods, it's hard to determine the real effect of the placebo. Most ADHD children have their medication dosages altered repeatedly over the course of their treatment, says David Rabiner, PhD, of Duke University and a spokesman for CHADD, an ADHD patient advocacy group.

"And previous studies suggest that kids who receive behavior treatment in conjunction with their medication, on average, are maintained on lower doses of medication," he tells WebMD. "So what is important for parents to know is that if a child needs to be on [ADHD] medication, and they would like their child to be managed on lower doses, there is evidence that if the child gets good behavioral intervention, they may be able to reduce the need for higher dosages. It would be unfortunate if it was interpreted from this study, and I know it's not the authors' intention, that the medication doesn't do anything and they could just cut their child's dosage in half."

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SOURCES: Research presented at the Pediatric Academic Societies annual meeting. James Bodfish, PhD, professor of psychiatry, University of North Carolina, Chapel Hill. Thomas Megerian, MD, PhD, attending neurologist, Behavior Neurology and Neuropharmacology, Children's Hospital of Boston. David Rabiner, PhD, senior research scientist, Duke University's Center for Child and Family Policy, Durham, North Carolina; spokesman, Children and Adults with Attention-Deficit/Hyperactivity Disorder.
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