1) To compare standard twice-daily methylphenidate (MPH) dosing with a single morning dose of MPH and of Adderall during a typical school-day time period, and 2) to conduct a dose-response study of the effects of a late-afternoon (3:30 pm) dose of MPH and Adderall on evening behavior and side effects.
Within-subject, placebo-controlled, crossover design.
Intensive summer treatment program with a comprehensive behavioral approach.
Twenty-one children with attention-deficit/hyperactivity disorder (19 boys and 2 girls), between the ages of 6 and 12 years.
Children received, in random order with daily crossovers, each of the following conditions: 1) placebo, 2) 0.3 mg/kg of MPH received 3 times, 3) 0.3 mg/kg of MPH received twice (7:30am and 11:30 am) with 0.15 mg/kg received at 3:30 pm, 4) 0.3 mg/kg of MPH received once in the morning only, 5) 0.3 mg/kg of Adderall received at 7:30 am and at 3:30 pm, 6) 0.3 mg/kg of Adderall once in the morning with 0.15 mg/kg received at 3:30 pm, 7) 0.3 mg/kg of Adderall received in the morning only.
Daily rates of behaviors in social and academic settings, and standardized ratings from counselors and teachers, were assessed for the hours between 8:00 am and 3:30 pm (a typical school-day). Relative sizes of the medication effects were compared hourly between first daily ingestion (7:30 am) and 4:45 pm to assess the time course of the 2 drugs. Effects of the 3:30 pm doses on functioning in the evenings at home were evaluated using parent ratings of behavioral and side effects.
A single morning dose of Adderall produced equivalent behavioral effects to those of MPH received twice-daily and behavioral effects of that single morning dose lasted throughout the school-day period. One morning dose of MPH was less effective than either 2 daily doses of MPH or 1 dose of Adderall, and seemed to wear off in the early to mid-afternoon. For some children a single morning dose of MPH maintained their behavior for an entire school day in the context of the summer treatment program. On parent ratings of evening behavior, 0.3 mg/kg of MPH at 3:30 pm was superior to 0.15 mg/kg at 3:30 pm, but there was no difference between the 2 doses of Adderall. Compared with placebo at 3:30 pm, only the 0.3 mg/kg dose of MPH caused significant improvement in parent ratings. In placebo versus Adderall comparisons, all doses, even the condition that consisted of Adderall in the morning and placebo at 3:30pm, produced a significant change in evening behavior.
The results show that, at least in the context of an intensive behavioral intervention, a single morning dose of Adderall had behavioral effects throughout an entire school day period that were equivalent to standard twice-daily MPH dosing. These results indicate that Adderall may be used as a long-acting stimulant for children for whom midday dosing is a problem. Further study including dose-response comparisons, effects in regular school settings, and direct comparisons with comparable doses of MPH and d-amphetamine will help to clarify the time course and relative advantages of Adderall.
Adderall Studies vs. The Real World
When will we see quality studies comparing more commonly used doses of Methylphenidate? If studies are done comparing equi-milligram doses of MPH and Adderall, the results will predictably favor Adderall. In my daily practice, doses of MPH of one milligram per pound per day, divided into two or three doses are routine. I use time release form whenever possible, and this not only reduces dosing frequency, but also improves effect.
I am also disturbed by the lack of second medication use in existing studies. Most of my patients, regardless of stimulant choice, need a second medication for optimal response. Psychotherapy and intensive school based interventions are woefully inadequate tools for many of my patients. Are my patients more seriously affected that they need Clonidine or Wellbutrin? Or, are the studies showing us the effects of incomplete treatment?
Is anyone out there interested in the real answers, or are we stuck with funding only from the people who make Adderall?
I'll do the study in my practice if anyone will fund it without strings, and without insistence on mono-therapy. Any takers?
Abraham Nussbaum MD FAAP
Enlightenment on ADHD TX
Pelham and colleagues are to be lauded on their elegant work elucidating some of the common beliefs and assumptions regarding the treatment of ADHD with two of the most commonly used drugs.
Four questions/comments: 1) Were you aware, forewarned, and/or disappointed that your critical work on such a germaine, important topic for the general pediatrician was being relegated to printed abstract status?
2) Did your subjects include any who were solely ADHD-inattentive form? Our experience has been that the majority of these inattentive children require about 1/2 the standard dosing of the hyperactive children, and that a single dose of amphetamine-products is often sufficient to cover them pharmacologically for the entire day.
3) Perhaps the reason that the study children only required a single dose (vis a vis the Swanson study) of Adderall to obtain reasonably good responses is that they were NOT in a classroom setting, which is inherently boring, has double the number of distractions (30 pupils), and requires sitting in a single seat for a much more prolonged period of time. Further, leisure activities (outdoor sports) comprised the majority of the day for your study patients. They were able to move from one locale to another.
In contrast, daily routine classroom activities and studies require tremendously more mental effort and struggles for these children with ADHD. More pronounced medication effects and differences possibly are more likely to be seen when ennui is frequent and mental challenges are constantly required. Possibly the Swanson study was conducted within a more typical classroom setting. Personally we have experienced that teachers usually complain that Adderall as a single dose "wears off" soon after lunch in the majority of our truly hyperactive-ADHD patients. Thus we most frequently prescribe a second half-dose of Adderall (or dexedrine spansules) at lunch in the very hyperactive child. Waiting for an afterschool dose would be intolerable in a typical demanding classroom setting for many of these children. The setting could explain why your patients performed so well with the lower range dose (0.3 to 0.6 mg/kg/dose) of MPH.
Also, hasn't an earlier study shown that a higher dose of stimulant medication is required to improve hyperactivity compared with distractibility.
4) I was glad to see that you primarily used teacher rating scales, as opposed to clinician global impression (CGI), to document medication response. It is alarming that newer pharmacologic trials of ADHD medications are relying solely on the physician observer and, in part, on parental questionaire to ascertain drug efficacy. Neither set of observers witness the child during intervals when concentration and sitting still is required, ie, the classroom.
Keep up the excellent, practical scientific work on such an important integral problem encountered by the general pediatrican.
Best regards SLB