Caroline Miller
Editorial Director
Child Mind Institute
Passions are running high on the issue of medication for kids with ADHD. We've seen a series of very emotional articles recently charging that too many kids are being diagnosed with the disorder—if it is a disorder at all—and especially that too many kids are being medicated.
It can be very disturbing for parents to be told they're overmedicating kids, especially by people who seem to have little direct experience with the medication—or the kids it's being prescribed to.
Because this has become a controversial issue, it's worth taking the time to examine what we really do know about ADHD and the effectiveness of medication. Is there sound scientific evidence about whether it works and whether it continues to work over time?
The biggest long-term study of treatment for children with ADHD, called the MTA study, treated nearly 600 children in the late 1990s for 14 months, to compare the effectiveness of several different protocols—medication, behavioral treatment, or both. That study showed clearly that medication reduced symptoms more effectively than behavioral therapies, and that adding the behavioral interventions didn't improve the result significantly over medication alone.
The MTA study showed that "stimulant medication deserves to be the first line treatment based on efficacy," as Dr. James Swanson, one of the study's authors, puts it, "when a family is concerned about the well-being of a child with ADHD tomorrow—or next month or next year." Dr. Swanson, a psychologist, is a prominent researcher in the field of ADHD and director of the Child Development Center at the University of California, Irvine, School of Medicine. This is generally accepted by members of the psychiatric community and other ADHD experts, and the results have been replicated in other, smaller studies that lasted as long as two years.
But there is less agreement on a related issue, which is whether kids develop tolerance to stimulant medications over time, and therefore need an increased dosage to get the same effect.
At the beginning of the MTA study, the optimum dosage of methylphenidate (the active ingredient in Ritalin) for each child was determined individually, and very methodically, over the course of the first month. Nonetheless, during the following 13 months of treatment there was pattern of kids needing increased doses to continue get the same effect, Swanson reports. In a follow-up analysis of the findings, Swanson writes that a dose increase was required in 54% of the medication-only group, with the dose per unit of body weight increasing on average 19%.
Roughly the same finding appears in a two-year study published in 2005 of more than 200 kids on Concerta, a delayed-release form of methylphenidate. The effectiveness of the medication was maintained successfully through the second year, but the dosage was increased an average of 15% per unit of body weight.
This finding reflects the experience of some clinicians. Dr. Roy Boorady, a Child Mind Institute psychiatrist who's been treating kids with ADHD for more than 15 years, says he often increases the dosage within the first several years of treating a child. "When I treat a child from, say, age seven, I find I have to increase dose, maybe 20%, to recapture the benefit. But after 15 or 16, I find that kids end up needing less, not more. " Dr. Boorady notes that this may be the result of ADHD symptoms waning, as they often do, in late adolescence, and it's also the case that as the teenagers' livers mature, they may be able to metabolize the medication more efficiently.
But not all clinicians report the same effect. Dr. Alan Ravitz, another veteran child and adolescent psychiatrist now at the Child Mind Institute, notes that
there could be other reasons for common increases in dosage over the years that don't imply tolerance: As a child gets older he faces increased expectations in school, higher demand for concentration. The child gets more aware of what the medication does and might want more of that feeling. He may be more tuned in to what other kids are doing, and feel competitive. Dr. Ravitz notes that he sees lots of patients who are adults and he does not typically need to increase the dose over the span of many years.
Dr. Rachel Klein, a clinician and researcher at New York University, also says she sees no pattern of needing to increase doses for kids with ADHD. Dr. Klein was one of the authors of a study published in 2004 in which 103 children with ADHD underwent treatment for two years, and they found no erosion of the benefit over time, Dr. Klein notes. As with the MTA study, no significant academic or behavioral improvement was gained by adding other psychosocial interventions to the medication regimen. "Significant benefits from methylphenidate were stable over two years," the authors wrote.
Dr. Klein acknowledges that there are shifts in an individual child's responsiveness to stimulant medications, but says there is no demonstrated pattern of diminished response. "It may happen in some cases," she says. "I've seen kids who lose the effect, and I've seen kids who didn't respond at one time and respond two years later. So there's variation, but on average that's not true."
In children who do need increased doses to maintain effectiveness, it's plausible that what's at work is the brain adjusting to the stimulant, which works by increasing the dopamine level in the brain, Swanson and others note. The brain could adjust by producing more receptors or more sensitivity in the receptors that remove dopamine from the system.
There is clear evidence that something like this happens, to some children, over a day of taking medication. Swanson and other researchers documented this effect, called acute tolerance, in a study published in 1999: Over the course of a day of continuous medication, kids need a higher dose in the afternoon to deliver the same effect as a smaller does in the morning. This insight led to the development of ascending-dose stimulant medications like Concerta, which delivers methylphenidate at the rate of 30% in the morning and 70% in the afternoon.
Does this suggest that a similar adjustment might be made over a period of months and years—one that doesn't disappear when the medication leaves the body at night? "It's certainly plausible that there is tolerance developing very slowly over time," says Dr. Stephen Hinshaw, another one of the authors of the MTA study: "We just don't know if what happens on the scale of 12 hours happens over 12 years. We just don't know. "
Dr. Hinshaw, professor of psychology at the University of California, Berkeley, notes that sometimes after years of effective treatment, a patient with ADHD needs to switch to a different medication, say from Concerta (methylphenidate) to Adderall (amphetamine) to maintain the effect.
One source of confusion in the discussion of long-term effectiveness of ADHD medications is a long-term follow-up to the 14-month MTA study, which checked in with participants periodically after they were no longer being treated as part of the study. Kids in the MTA study who were in the medications group, when contacted later, had lost half the benefit by the end of two years, and all of it by the end of three years.
Dr. Swanson, one of the authors of the follow-up analysis, notes that the dwindling benefit was seen not only in the whole group—many, if not most of whom had abandoned the treatment with medication—but within the subgroup of kids whose parents continued with medication. He sees that as evidence of tolerance developing. Dr. L. Alan Sroufe, writing in a widely circulated piece in the New York Times, used this MTA follow-up analysis to argue that stimulant medications had been shown to have no long-term value.
But Dr. Hinshaw and other disagree. Dr. Hinshaw notes that the MTA follow-up was what researchers call a "naturalistic" follow-up: it's not controlled, and the treatment kids received from practitioners in their communities wasn't standardized in any way. It's not scientifically meaningful, Dr. Hinshaw and others argue, and the decline in results from medication could just as well reflect the fact that the medication wasn't managed well.
During the original 14 months, the titration was specific to each child, each participant saw a doctor once a month for a 20-minute visit, 10 minutes of which was "alone time" with the doctor, and the doctor also spoke to the child's teacher to monitor his progress once a month. Community care, Dr. Hinshaw notes, often means you see a pediatrician once every five months, there is no communication with teachers, and no expert titration. The level of care just isn't similar to that in the study.
Also, Dr. Hinshaw notes, when you're in a naturalistic phase the children who continue to get medication are an admixture of upper-middle-class kids whose families can afford more treatment and families whose kids have very severe symptoms. These biases invalidate the value of the follow-up data.
"That's not an experimental study," Dr. Klein says. "We don't know that the kids actually stayed on meds. Was the dosage properly monitored? Those who stayed on the medications the longest may have been the ones most severely impacted by their symptoms. What we know is that when you do control the treatment it works over time."
The larger issue raised by this disagreement is whether the possibility of brain adaptation to medication for ADHD undermines their effectiveness.
Dr. Swanson concludes that evidence of tolerance is problematic for long-term use. "Dose increases are an effective strategy to overcome this loss, at least in the first one or two years of treatment," he writes. "However, this may not be a viable long term strategy for the majority of ADHD youth prescribed CNS stimulants."
His concern is underscored by two other recent studies based on brain scans that suggest that use of stimulant medications may increase the density of what are called dopamine transporters (DAT), which are the primary target of stimulants like methylphenidate. The studies were led by Dr. Gene-Jack Wang, a neuroscientist and chair of Brookhaven National Laboratory's Medical Department, and Dr. Nora Volkow, a psychiatrist and scientist who is director of the National Institute on Drug Abuse (NIDA) at the National Institutes of Health. Brain scans of children who had been on methylphenidate for a year showed an increased density of transporters, which they hypothesize could correspond with a declining clinical effect of the medication on ADHD symptoms. Meta-analysis of other studies, adds Dr. Swanson, also showed a strong association between prior stimulant exposure and DAT density.
What Dr. Swanson and others agree on is that the possibility of developing tolerance over the long term doesn't undermine the value of medication for children with ADHD in the short run, when it may very significantly improve their lives.
As Dr. Michael Milham, a neuroscience researcher and and child psychiatrist at the Child Mind Institute, puts it: "If some kids do develop tolerance to the medication, so what? Lots of good medications become ineffective eventually, from SSRIs to blood pressure medications. That doesn't mean we don't use them for as long as they work."
Swanson concurs: "We don't need to justify giving medication to kids based on what it's going to do 10 years from now. The parent comes to us with a child who is getting kicked out of school. A child who doesn't have any friends. The parent wants to know, what can we do now—for the next year of my child's life? Medication's going to be the best treatment. And that's complete justification for giving it."
Published: April 16, 2012
http://www.childmind.org/en/posts/articles/2012-4-16-facts-adhd-medications#.T5QtQjGKZYo.email
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