HOMEResourcesArchive of Brown Newsletter
| Long-term data suggest changes in effectiveness of stimulant medication over time |
| Researchers taking part in the National Institute of Health (NIMH) Multimodal Treatment Study (MTA) of Children with Attention-Deficit/Hyperactivity Disorder, conducted a 24-month follow-up designed to examine whether treatment effects persist. They found that consistent use of stimulant medication was associated with maintenance of effectiveness, while those who changed treatment or stopped medication treatment deteriorated. The MTA is an ongoing, longitudinal randomized clinical trial that is studying several issues surrounding the use of stimulant treatment in children with ADHD. In 1995, the MTA recruited 579 elementary school children ages 7 to 9, who were randomly assigned to one of four treatment modes: (1) medication management alone; (2) behavioral treatment alone; (3) a combination of both medication and behavioral treatment; or (4) routine community care. After 14 months (end of treatment) the researchers found that medication management alone was superior to behavioral treatment alone and to routine community care that included medication. The combination treatment did not yield significantly greater benefits than did medication management for core ADHD symptoms, but the researchers say it may have provided modest advantages for non-ADHD symptom and positive functioning outcomes. Now, The MTA Cooperative Group has published two follow-up articles in the April issue of Pediatrics, reporting on what they found after the children had been in their natural settings for 10 months beyond their 14 months of intensive intervention. At this 24-month assessment, 540 of the 579 subjects were evaluated (a 93% retention rate). Methods and results Two different kinds of analyses were used to get the best possible information from the data. First, the intent-to-treat analyses (ITT) analyses, which is considered the "gold standard" of randomized controlled trials, and second, medication status reported on the Services for Children and Adolescents Parent Interview. "The intent-to-treat analyses actually analyzes the effect of what participants are assigned to get, [even if they fail to comply]," explains James M. Swanson, Ph.D., one of the principal investigators of the MTA research. "You're not analyzing whether they actually do what you ask them to do, you're just analyzing the effect of telling people what to do. So the actual treatment isn't the critical thing." In other words, you measure the effect on each group by whether they were assigned to get medication, behavioral treatment, combination treatment, or community care, but you don't know whether they actually complied with the instruction you gave them. (This kind of ITT analysis is necessary to accurately compare the different treatment arms in randomized controlled trials. If ITT analyses were not used, then only those who complete their assigned treatment are counted and this would bias the results - e.g., those who dropped out might be more likely to be not responding to their treatment condition). Swanson, professor of pediatrics at the University of California, Irvine, says the ITT analyses showed group differences on ADHD symptoms ratings, suggesting that the medication management group and the combined treatment group had better outcomes than did the behavioral treatment and community treatment groups at 24 months. However, the effect size (ES) for the medication and combined treatment groups deteriorated 50% from the end of treatment at 14 months (ES: ~0.6) to the follow-up at 24 months (ES: ~0.3). Therefore, some of the children in the medication management and the combined treatment group lost some of the initial benefits (14 months), when seen in follow-up (24 months). The behavioral treatment group and the community care group did not show deterioration. Even so, all four groups still had lower ratings of ADHD and ODD symptoms than at baseline, indicating evidence of some persistence of the MTA treatment effects. Swanson explains that while that 50% reduction makes it appear that the effect of medication is decreasing, the reduction in effect size is a result of the participants now being away from the rigors of the controlled treatment phase. In their more natural settings, they may or may not continue to follow their assigned treatments properly. "So it looks like the effect of medication is going away, but after the randomization and treatment phase is completed, people tend to go and do other things than what you had asked them to do in the study," says Swanson. Medication vs. no medication For the second measure, the medication status reported on the Services for Children and Adolescents Parent Interview at the 14-month assessment and at the 24-month follow-up assessment was used to form naturalistic subgroups for 521 of the 540 participants. That is, regardless of initial random assignment, if medication use was reported at an assessment point, then the code for that case was "Med" for that point; if not, then the code was "NoMed." This produced the following four naturalistic subgroups: 1. *Those who were initially in the randomly assigned medication group, and continued to take their medication after the 14-month treatment phase were called the Med/Med subgroup (n=255). This group showed modest deterioration reflected by an increase in average Swanson, Nolan, and Pelham Scale (SNAP) ADHD ratings of 0.15 points. The ADHD and ODD ratings increased nominally during follow-up (0.15 and 0.08, respectively), which could be interpreted as a reduction in the effects of stimulant medication over time. 2. *Those who were not in a randomly assigned medication group and reported not taking medication fter the 14-month treatment phase were called the NoMed/NoMed subgroup (n=139). This group showed modest deterioration reflected by an increase in average SNAP-ADHD ratings of 0.10 points. Small increases in ADHD and ODD ratings (0.10 and 0.08, respectively) were observed in this subgroup. [*The researchers say that the slight deterioration in both of these subgroups seems to characterize the natural history of the disorder independent of treatment with medication. This suggests that either consistent pharmacologic and behavioral treatments maintained most of their effects over time or that some other variable was operating consistently across these groups during the first two years of the MTA.] 3. Those who were initially in the randomly assigned medication group, but stopped medication after the 14-month treatment phase were called the Med/NoMed group (n=76). This group showed the largest deterioration, reflected by an increase in average SNAP-ADHD ratings of 0.33 points. 4. Those who were not in a randomly assigned medication group but reported starting medication after the 14-month treatment phase were called the NoMed/Med subgroup (n=51). This group showed the opposite pattern (improvement), reflected by a decrease in average SNAP-ADHD ratings of 0.15 points. In summary, although definite statistical differences persisted from the original study treatment assignment, after subsequent (follow up) medication use was controlled for, the "clinical significance of the medication algorithm may be modest." There are some children (and their families) who "receive maximum medication benefit only when it is accompanied by fairly intensive support and regular contact with their doctor, and/or a behavior therapist, whereas others may continue to benefit even after this support is withdrawn." "It looks like medication continues to work as long as you take it," says Swanson. "And if you start it after 14 months then it starts working and if you stop it after 14 months it stops working. It actually turns out to be pretty much what people with any good common sense would think." For further reading: Arnold LE, Chuang S, Davies M, et al.: Nine Months of Multicomponent Behavioral Treatment for ADHD and Effectiveness of MTA Fading Procedures. Journal of Abnormal Child Psychology 2004; 32(1):39-51. E-mail: Arnold.6@osu.edu. MTA Cooperative Group: National Institute of Mental Health Multimodal Treatment Study of ADHD Follow-up: 24-Month Outcomes of Treatment Strategies for Attention- Deficit/Hyperactivity Disorder. Pediatrics 2004; 113:754-761. E-mail: jmswanso@uci.edu. Richters JE, Arnold LE, Jensen PS, et al.: NIMH collaborative multisite multimodal treatment study of children with ADHD: I. Background and rationale. JAACAP 1995; 34(8):987-1000. E-mail: Arnold.6@osu.edu. |