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A Procedure for Predicting Response to Stimulant Medication Treatment
When considering the use of stimulant medication treatment for their child, parents often wonder whether it is possible to know in advance if it will work and if there will be any adverse side effects. To date, the answer to this question has been that it is not possible to determine such outcomes. Thus, although most children with ADHD will show clear reductions in ADHD symptoms when stimulant medication is administered appropriately, results from prior research suggest that predicting the response for individual children is not possible. The same holds true for predicting which children may experience unpleasant side effects.
Making accurate predictions would be useful for several reasons. First, if parents reluctant to consider medication could be assured that it would help their child, they might be more willing to give it a try. Second, for those children who were unlikely to benefit and were likely to experience adverse reactions to the medication, an unpleasant and ineffective treatment experience could be avoided
A study appearing in a recent issue of the journal Biofeedback provides intriguing evidence that such predictions may be possible (Monastra, V., vol. 28, 2000). A bit of background information is necessary before discussing these important findings.
In an issue of Neuropsychology, Dr. Monastra and his colleagues demonstrated that individuals with ADHD showed a distinctive pattern of results on a quantitative electroencephalography (QEEG) reading.
QEEG is a procedure in which the pattern of electrical activity in different brain regions is recorded and measured. The research of Dr. Monastra and others indicates that most individuals diagnosed with ADHD via traditional methods, such as diagnostic interviews and standardized behavior rating scales, show a QEEG pattern that indicates under-activity in prefrontal brain areas. It is suggested, although not yet confirmed, that under-activity in this brain region causes the behavioral symptoms that individuals with ADHD display. In contrast, very few individuals not showing the behavioral symptoms characteristic of ADHD showed this same pattern of cortical under-activity. Of course, because ADHD is currently diagnosed based on the presence of observable behaviors rather than any particular QEEG pattern, not all individuals who meet diagnostic criteria for ADHD show this pattern of cortical slowing in their QEEG results. This fact is the basis for the current study.
Participants in this study included 144 individuals between the ages of 6 and 20 who were diagnosed with ADHD using DSM-IV diagnostic criteria. QEEG recordings were then conducted with these individuals. As expected, the majority (103) demonstrated the anticipated cortical slowing on their QEEG. The other 41 individuals did not. Remember, all 144 had already shown a sufficient number of inattentive and/or hyperactive-impulsive symptoms to warrant a diagnosis of ADHD. The difference between the two groups was not in the behavioral symptoms they displayed, but rather, whether a particular type of QEEG result was received.
After the diagnostic and QEEG procedures, all patients received a careful trial of stimulant medication. Participants were started on a low dose of methylphenidate (the generic form of Ritalin) two times per day and were given up to a maximum dose of 20 mg twice per day as needed. If methylphenidate was not helpful, a switch was made to Adderall, and the titration procedure began again. Careful measures were taken to determine whether each individual obtained clinically significant benefits from stimulant medication. Those who responded to medication (either medication or any dose) received behavior ratings on an ADHD rating scale from parents and teachers that placed them in a non-clinical range, and they obtained a "normal" score on a computerized test of sustained attention while on medication. Individuals who did not attain such benefits on either medication were classified as non-responders.
Results
Of the 103 participants who showed the cortical slowing pattern on their QEEG, 96 responded positively to stimulant medication. In contrast, of the 41 participants who showed no cortical slowing on their QEEG, none responded positively to methylphenidate or Adderall. (Remember, a positive medication response was defined as normalized behavior ratings from parents and teachers as well as a “normal” performance on a computerized test of sustained attention. The criterion for determining positive responders was quite strict.) In addition, each of these 41 non-responders exhibited at least 3 of the following side effects: headaches, increased irritability, sedation, rapid speech, increased impulsive behaviors, or increased hyperactivity. These side effects were rarely reported among those who responded positively to medication.
When efforts were made to predict medication response according to the number and severity of ADHD symptoms or performance on the computerized attention tests, no accurate predictions were achieved. Thus, it was only the indication of cortical slowing on the QEEG that enabled accurate predictions to be made.
Summary And Implications
The results of this study are impressive. Although almost every participant with ADHD who showed cortical slowing obtained substantial benefits from medication, those showing the behavioral symptoms of ADHD without this QEEG pattern never obtained a similar benefit. While these results require careful replication, they are exciting. Not only may QEEG prove to be a useful tool to assist in the ADHD diagnostic process, but it may also help to identify individuals showing the behavioral manifestations of ADHD who are (and are not) likely to benefit from stimulant medication.
As noted earlier, this would be quite helpful for treatment planning purposes. Although not examined in this study, it is also possible that individuals not showing the cortical slowing pattern would have responded to a different class of medication, such as an antidepressant. This would be an interesting question to explore in subsequent research.
These results also highlight something that is important for clinicians and parents to be aware of: the behavioral symptoms of ADHD can have different origins. Typically, recently published research suggests that individuals diagnosed with ADHD using the current behavioral criteria will show the pattern of cortical slowing that researchers like Dr. Monastra have identified. However, other individuals showing the ADHD behaviors will not. This suggests that some individuals with ADHD have developed their symptoms for other reasons. Accurately identifying those reasons may be key to providing appropriate treatment.
There is other published research which suggests that dietary factors, elevated lead levels, deficiencies in trace minerals like iron and magnesium, along with a variety of other factors may be important contributors to ADHD symptoms in individuals without the pattern of cortical slowing. When specific causes are identified for an individual, it is often directly linked to a specific treatment. For example, providing magnesium supplementation to children with ADHD found to be deficient in magnesium. This is an area where additional research is needed, and it is important to note that such ideas are not widely accepted within the medical and scientific community. I will include such studies in future issues of Attention Research Update as I become aware of them. Should you be aware of work in these areas that I may have missed, I would appreciate your letting me know.
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.