Adderall vs. Methylphenidate in the Treatment of ADHD

During the past year there have been two studies published in which Adderall - a relatively new medication used for treating ADHD - has compared favorably to methylphenidate (i.e. the generic form of Ritalin) for reducing the symptoms of ADHD. In these studies, Adderall was found to yield a comparable - or even more favorable response - than methylphenidate for most children, and children required less frequent dosing with Adderall.

There were several important limitations of these prior studies, however, that mitigate the conclusions one can make about the superiority of Adderall. First, both studies compared certain fixed doses of Adderall to fixed doses of methylphenidate. What this means is that an individualized procedure to determine the optimum dose of medication for each child - based on feedback received about the child's performance on different doses - was not employed. This is important because such a procedure helps to insure that a child is getting the maximum possible benefits from medication. This is also closer to what should happen in actual clinical practice. Second, children in these studies were not randomly assigned to receive either Adderall or methylphenidate, but received one or the other - or both - based on a variety of considerations. Random assignment (i.e. it is strictly chance whether a child gets placed on one medication or the other), however, is the best procedure to use for trying to determine whether one medication tends to produce a superior effect to the other.

A study published last month in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACP) takes an important step in addressing the limitations of prior work (Plizka, S.R. et al., (2000). A double-blind, placebo- controlled study of Adderall and methylphenidate in the treatment of ADHD. JAACP, 39, 619-626.) The focus of this study was to provide the most thorough evaluation to date of the relative efficacy of Adderall vs. methylphenidate for the treatment of ADHD in elementary school children.

Participants in this study were 58 children diagnosed with ADHD, the majority of whom had received no prior medication treatment. The average age of children was approximately 8 years old and both boys and girls were included. (Unfortunately, the breakdown of girls and boys in the sample was not provided). To participate in this study, parents had to provide consent for their child to be randomly assigned to receive either methylphenidate, Adderall, or a placebo (i.e. a placebo is something that looks like real medication but is really not) for a 3-week trial. (The child received only one of these 3 possibilities during the entire 3-week trial.) Neither the child, the child's parents, nor the child's teacher were aware of what the child was receiving during the trial.

Prior to commencing the trial, baseline ratings of children's behavior were obtained from both parents and teachers. During the initial week of the trial, teachers completed behavior rating forms twice per day, each day - once to report on the child's behavior and academic performance during the morning and once to report on behavior and school work during the afternoon. In addition, at the end of the week, parents were interviewed over the phone about their child's behavior during the after-school hours for that week. Parents were also asked to rate the severity of a variety of possible side effects that they may have observed during the week. These teacher and parent ratings were then reviewed by a psychiatrist who was also blind to the child's medication status. Based on the ratings, this psychiatrist decided whether an adjustment to the child's medication needed to be made for the second week (e.g. increasing the dose, adding a second dose during the school day and/or after school).

So, for example, some children on Adderall may have done so well during the initial week that no adjustment to dosage was made after reviewing the first week's ratings. Other children in Adderall, in contrast, may have had their dosage increased. The same would be true for the children on methylphenidate. Even for children on placebo, a recommendation for adjustment could be made (recall that the psychiatrist making the recommendation did no know whether the child was on a placebo), although this would result in nothing more than the placebo being administered for another week.

A similar procedure was followed during the second week, at the end of which another adjustment was made if warranted. This procedure thus provided the opportunity to adjust the child's dosage for 2 successive weeks using carefully collected data from parents and teachers. Finally, parent and teacher behavior ratings and parent side effect ratings were then collected once again at the end of the final week. In addition, a psychiatrist who was blind to the child's medication status provided an overall rating of the child's improvement using a standardized scale designed to assess treatment improvement. This rating was made based on an individual interview with the child and his/her parents, as well as reviewing the rating scale data collected during the trial.

In theory, this procedure for adjusting dosage after the first 2 weeks based on the behavior rating and side effects data should have resulted in the child being placed during the 3rd week on a dosage regime that was best suited for him or her. Thus, this should allow for a "fair" comparison of the relative efficacy of Adderall vs. methylphenidate for treating ADHD symptoms in school-age children.

Results

For each source of outcome data (i.e. teachers, parents, and psychiatrist) analyses were conducted that compared children in the 3 groups (i.e. Adderall, methylphenidate, and placebo). The results of these comparisons are summarized below.

Teachers

Teacher behavior ratings showed - as expected - that children receiving either Adderall or methylphenidate did better than children on placebo. This, of course, has been documented in numerous prior studies and the magnitude of the difference were comparable to what has been found before.

Of more interest, however, is that children receiving Adderall fared significantly better according to teachers than children receiving methylphenidate. This was true for ratings of ADHD symptoms specifically and for ratings of aggressive/ disruptive behavior.

Parents

In contrast to the results for teachers, no significant difference was found when parents ratings were analyzed. In other words, neither Adderall nor methylphenidate were found to be superior to placebo when parent ratings of children's behavior during the evening were analyzed.

This can not be explained by the fact that children were not receiving medication to cover the after-school hours when parents would have the opportunity to observe them. The reason why this is not a viable explanation is that when parent ratings during week 1 or 2 indicated that problems related to ADHD were clearly evident during evening hours, an adjustment would have been made to provide the child with the additional dose needed to cover the after-school period. Instead, the authors suggest that the reason no significant effect was found for the parent ratings is that there was such a large placebo effect for parents. In other words, even parents whose children were receiving placebo reported substantial improvements relative to the initial ratings taken at baseline. Because so much improvement was reported by parents for children receiving a placebo, it was difficult for the medication to look significantly better.

Psychiatrist

As noted above, a psychiatrist also provided an overall rating of each child's improvement based on an interview conducted with the child and family, and reviewing the behavior rating scale data. Children were considered to have shown a positive response (i.e. significant improvement) during the trial based on the score they received on this rating.

Using this criterion, 90% of the children in the Adderall group were judged to be responders. This compares to 65% of children receiving methylphenidate and 27% of children who received placebo. This difference in response rate between Adderall and methylphenidate was statistically significant, as was the difference between methylphenidate and placebo. (The fact that over 25% of children receiving placebo were rated as showing significant improvement highlights the need of conducting placebo-controlled trials to determine medication response. Otherwise, children who get no real benefit from medication above and beyond a placebo response may be maintained on the meds for a sustained period of time.)

Final Dosing Regimen

In addition to looking at how the behavioral outcomes compared for children on Adderall and methylphenidate, it is also instructive to look at the dosing regimens that children were on at the end of the trial. Seventy percent of the children receiving Adderall required only a single dose per day to cover the entire day, while 30% required a second dose after school to cover the evening hours. None of the children on Adderall were judged to have needed a second dose during the school day - an important finding in that taking medication at school can be a source of concern for some children and parents.

For the children on methylphenidate, 85% received 2 or more doses per day. Of the 13 who were judged to be positive responders according to the psychiatrists ratings, 6 required a second dose during the school day. Thus, about half the children judged to have responded favorably to methylphenidate needed to take the medicine during school.

In terms of the total daily dose, children in the Adderall group received an average of 12.5 mg/day compared to 25.2 mg/day for children receiving methylphenidate.

Side Effects

After each week of the trial, parents provided ratings of the most commonly reported side effects of stimulant medications. For each of 11 side effects, the percentage of parents reporting that the adverse effect was either moderate or severe was a minority. Although there was no significant difference in the number of children for whom parents reported moderate to severe side effects, there was a tendency for children receiving Adderall to show more stomach problems and mood changes (i.e. sadness and/or irritability). Approximately 25% of children receiving Adderall were reported by parents to show such effects.

It was interesting to note the parent reports of the side effect "Gets wild when medication wears off", a relatively common complaint of parents whose children take stimulant medication. Thirty-five percent of parents whose child received Adderall reported this concern as did 40% of parents whose child received methyl- phenidate. This would seem like a real problem. For children receiving placebo, however, this same concern was reported by 44% of their parents. Thus, this also illustrates one of the potentially important benefits of conducting placebo-controlled medication trials: such trials can help to determine whether an apparent side effect of medication is really just a placebo effect.

Summary And Implications

The results of this study suggest that Adderall may be a better initial choice of medication for children with ADHD relative to methylphenidate. In this study, the behavioral effects of Adderall were generally greater than those produced by methylphenidate, and they also lasted longer. This means that most children treated with Adderall required less medication and fewer doses to achieve better results. In particular, none of the children treated with Adderall needed to take a dose during the school day during this trial, something required by a number of children treated with methylphenidate. One potential concern is the possibility that Adderall may possibly be more likely to lead to stomach aches and mood changes than methylphenidate. Thus, these potential side effects would need to be monitored carefully.

These results should not be interpreted to mean that any particular child will do better on Adderall than methyl- phenidate, as this is clearly not the case. Many children will do equally well on both types of medication, some will do equally poorly on both, and some will do better on methylphenidate than Adderall. Instead, the data should be interpreted to suggest that if a child is going to be started on medication to treat ADHD - and this is an entirely separate decision - then Adderall is probably a good medication to begin with. Replicating these results with a larger sample would lend even greater confidence to this recommendation. It would also be nice if a study was done that directly compared Adderall to Ritalin, as there have been some reports that Ritalin may be superior to its generic form (i.e. methylphenidate).

If your child is currently on methylphenidate or Ritalin and is doing well, I would not take these data to mean that you should switch to Adderall. For a child on a stable medication regimen and doing well, the only reason I am aware of to do this would be if the child needed to take medication during the school day, and this was a source of concern. In this case, it appears that Adderall will often eliminate the need for this in school dosing. Thus, should this be your circumstance, it may be an option worth discussing with your child's physician. Remember, though, there is no guarantee that Adderall will prove to be as effective for your child, so one would need to carefully and systematically monitor how a child responded to the switch.

Note: This article originally appeared in Attention Research Update, an online newsletter written by Dr. David Rabiner, a Duke University psychologist and former member of CHADD's Professional Advisory Board. You can learn more about Attention Research Update and sign up for a free subscription at www.helpforadd.com.

Reproduced with permission of David Rabiner, Ph.D. - HelpforADD.com