The Latest MTA Study in Context: What It Tells Us about the Role of Medication in ADHD Treatment

When last month’s MTA follow-up study suggested that stimulant medications don’t help reduce ADHD symptoms in the long run, parents and adults diagnosed with the disorder were unsettled. ADHD expert Stephen Hinshaw, Ph.D., weighs in with his perspective.
ADHD News Feed | posted by Devon Frye, Stephen Hinshaw, Ph.D.

April 6, 2017

The Multimodal Treatment of Attention Deficit Hyperactivity Disorder (MTA) study — one of the largest and longest running ADHD treatment studies that has been conducted to date — released data in March indicating that stimulant medications, even when taken consistently from childhood to adulthood, have no effect on ADHD symptoms in the long term. Though the results concerned many, expert Stephen Hinshaw, Ph.D., pointed out that the absence of randomized trials in the observational phase of the MTA study makes it difficult to accurately assess medication’s effectiveness. As a result of this and other aspects of the study’s design, Hinshaw says that parents and adults shouldn’t be discouraged from using medication as part of a well-designed treatment plan.

Since the late ’90s, ADHD experts and patients alike have waited eagerly for the follow-up results from the MTA — generally published every two years or so — to provide new insights into treatment and how symptoms progress as children with ADHD turn into adults with ADHD. The first phase, the results of which were published in 1999, examined treatment options for 579 children between the ages of seven and 10 who had been diagnosed with ADHD. The children were randomly assigned to one of four groups — medication, medication plus behavior therapy, only behavior therapy, or “community care,” which was organized and overseen by the children’s parents. The children were treated for 14 months — with medication taking a decisive stand as the most effective ADHD treatment — after which formal treatment ended. However, the children were still treated for ADHD at their parents’ discretion and observed by the researchers, with follow-up data published periodically.

One of the most publicized follow-up releases was published in August 2007, focusing on 485 of the original 579 children. The researchers were surprised to find that among children who continued to take ADHD medication consistently, the stimulants that had worked so well at first started to lose their effectiveness around three years after treatment started. On top of that, it was revealed that stimulants slowed the patients’ growth — confirming a side effect long feared by researchers and parents of children who were treated with stimulant medications. Another follow-up, in September 2016, found that more than 60 percent of the children — regardless of their medication use — continued to show ADHD symptoms into adulthood. More than 40 percent still experienced “significant impairment” from their symptoms.

The latest follow-up, released in March 2017, further confirmed the association between stimulant medications and reduced height; patients who took stimulant medications consistently were an average of 2.36 centimeters shorter than their peers who had stopped taking medication or who took it only sporadically. But, in a confounding twist, the two groups (those who took medication consistently and those who didn’t) showed no difference in symptom severity — though members of the former had, on average, taken more than 100,000 mg. of stimulant medication over the course of their lifetimes.

The results raised questions about long-standing treatment norms that prioritize stimulants as first-line treatments, leading some parents and adults to worry that taking ADHD medication — especially over the long term — might do more harm than good. Others aren’t ready to disavow stimulants just yet, wondering if other factors like symptom severity or environmental triggers might be playing a role. To address readers’ concerns regarding stimulant use, ADDitude asked Stephen Hinshaw, Ph.D., a world-renowned ADHD expert, a member of ADDitude’s Scientific Advisory Board, and one of the MTA study’s investigators, to tackle both sides of this debate and put the latest MTA results in context:

“The 16-year data from the MTA study reveal that, even though an optimal stimulant medication regimen during childhood for children with carefully diagnosed ADHD led to quick and efficacious symptom improvement in the vast majority of cases, when the intensive medication management was stopped after the 14 months of the original randomized clinical trial, medication was used less intensively and systematically over time.

“As well, the initial symptom-related gains dissipated. Indeed, by adolescence, most of the originally medicated youth had stopped receiving it, and their symptom levels reverted to those of children who had not received the earlier systematic medication intervention. Even when the sample was subgrouped by ‘lifetime exposure’ to medication, those with relatively high doses across many years fared no better, overall, than those with less consistent medication practices.

“What does all this tell us? Clearly, no one can ethically or feasibly perform a randomized trial of medication versus placebo that extends throughout childhood and adolescence. Yet, in absence of such, we're left with studies of ‘naturalistic subgroups’ characterized by different patterns of medication use. It's impossible to know, however, whether these subgroups differ solely on the medication they've received or on other factors that might well influence the outcome.

“For example, do the most severe cases continue to receive medicine, or those with the most motivated families, including those with better health coverage? In cancer research, randomized trials reveal the benefits of chemotherapy and radiation. But in naturalistic follow-up studies, these treatments are associated with worse outcomes, including death, because people with the most severe forms of cancer receive more intensive treatments. In short, naturalistic follow-up studies can never tell us the precise influence of treatments, unconfounded by such biases, despite scientists' attempts to ‘equate’ the subgroups.

“For ADHD, it could be that if optimal medication practices were maintained for many years, improvement would last. Yet, in the real world, it's increasingly difficult to sustain such practices. It could also be that, for at least some people with ADHD, continuous medication over time leads, ultimately, to some ‘burnout’ of the dopamine receptors that are the immediate targets of the medication. It could well be the case that measures of ADHD symptom reduction aren't the best measure of medication responsiveness. In fact, to reduce comorbid conditions linked to ADHD and to enhance academic performance, social skills, and family discipline practices, combinations of medication plus parent management, school consultation, and social skills interventions are optimal (Hinshaw & Arnold, 2015).

“Finally, just because medication may not, in and of itself, lead to complete reduction of ADHD and related impairments over time, this should not signal that families should never start it. Medication-related improvement during childhood, adolescence, or adulthood can boost performance in social and academic and vocational domains, reduce risk for accidental injury, and lead to improved quality of life (again, particularly when combined with other evidence-based treatments). It's best not to view medication treatment for ADHD as an automatic panacea or with despair. Above all, your clinician must work with you to carefully monitor medication — getting the right type of medicine and the correct dose — and evaluating its benefits as part of a holistic set of interventions.”


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