Although stimulant medication has been shown to be a helpful treatment for many children and adolescents with ADHD, there remains considerable interest in developing other medicinal options.  This is due to the fact that not all children with ADHD respond positively to stimulants and some experience adverse reactions that preclude their use.  In addition, although stimulants are generally believed to be extremely safe medications, they are classified as controlled substances and many parents have concerns about the long-term effects of their use.

Although several other medications are sometimes prescribed for ADHD (e.g. tricyclic antidepressants, clonidine, buproprion), the FDA has not yet approved any non-stimulant medication for use with children.  During 2002, however, FDA approval is expected for a new non-stimulant ADHD medication called Atomoxetine.  A study published in a recent issue of Pediatrics (Michelson, D. et al., (2001). Atomoxetine in the treatment of children and adolescents with ADHD: A randomized, placebo-controlled, dose-response study, Pediatrics, 108) presents data from a large, multi-site trial of the efficacy of this new medication.  Because this medication is likely to be introduced with considerable fanfare, it is important for parents and professionals to have a good understanding of the data supporting its use.

Participants in this study were 297 8 to 18 year-old children (212 boys/85 girls) at 13 outpatient investigative sites across the country.  All participants met DSM-IV criteria for ADHD, confirmed using a structured psychiatric interview.   Approximately 65% displayed inattentive and hyperactive/impulsive symptoms with most remaining participants showing predominantly inattentive symptoms. In addition to meeting formal diagnostic criteria, all participants had to have a symptom severity score on the ADHD Rating Scale in the top 7% for children of their age and gender.  (The ADHD-RS is an 18-item scale in which parents rate the severity of each of the 18 symptoms of ADHD listed in DSM-IV).  Seventy percent of the children had previously been treated with stimulants.

Before starting treatment, baseline measures were collected using the ADHD-RS -- the primary outcome measure used in this study -- along with several additional measures.  These measures included the Conners Parent Rating Scale- Revised (CPRS-R), the Clinical Global Impressions of Severity (CGI-S -- a measure used by clinicians to rate the severity of a child's symptoms), and the Child Health Questionnaire (CHQ). The CHQ is a parent-rated health outcome scale in which parents rate the well being of their family, themselves, and their child.

After baseline assessments were completed, participants were randomly assigned to one of 4 conditions: placebo, low dose (.5 mg/kg), middle dose (1.2 mg/kg), or high dose (1.8 mg/kg).  Atomoxetine was administered as equally divided doses in the morning and afternoon.  Children in the middle- and high-dose conditions began at the .5 mg/kg dose, then had their dosage increased at weekly intervals over a 3 to -4-week period.  Treatment continued for 8 -weeks, at which time the measures administered at baseline were again administered to determine treatment effects.

RESULTS

Overall, results indicate that Atomoxetine had a beneficial effect on both the primary symptoms of ADHD and associated impairments.  At both the middle and high doses, reductions in ADHD symptoms reported by parents were significantly greater than those for the placebo condition.  This was true for both inattentive symptoms and hyperactive/impulsive symptoms and for both older and younger participants.  The latter is an important finding in that it indicates Atomoxetine is helpful for adolescents with ADHD as well as children.

In addition to these beneficial effects on core ADHD symptoms (i.e. inattention and hyperactivity/impulsivity), parents' reports also indicated a significant reduction in oppositional behavior.  This was true across all 3 doses.  Parents' reports on the Child Health Questionnaire indicated that improvements in social and family functioning were superior among Atomoxetine patients when compared with those in the placebo group.  Thus, Atomoxetine treatment was associated with functional improvement that clearly went beyond the core symptoms of ADHD.

Atomoxetine was well tolerated by participants at all 3 dosage levels. Adverse reactions did not occur any more frequently among children treated with Atomoxetine than among those in the placebo group.  There was a trend, however, towards parents reporting greater sleep difficulties and appetite reduction among children treated with Atomoxetine, particularly at the highest dosage level.

Although these results are encouraging, it is important to recognize that many children treated with Atomoxetine continued to display elevated levels of ADHD symptoms.  The average score on the ADHD-RS at the end of the 8-week study was still in the top 7% for children of the same age and gender.  This means about half of the participants treated with Atomoxetine continued to show ADHD symptoms that were at or above the initial cutoff established to qualify children for the study.  This is consistent with post-treatment results for the Clinical Global Impressions Ratings of Severity (CGI-S), in which, according to clinicians' ratings, only half of the participants had symptoms that were considered absent, minimal, or mild.  Thus, half the children continued to show symptoms judged to be moderate or severe.

SUMMARY AND IMPLICATIONS

Results from this study indicate that Atomoxetine will be a valuable new treatment option for children and teens with ADHD when it becomes available. As noted above, this is expected to occur during 2002.  Because Atomoxetine will be the first non-stimulant specifically approved for the treatment of ADHD, and will not be classified as a controlled substance, it is likely that this medication will generate considerable interest.

Although this study demonstrates the clinical benefits of Atomoxetine, it is important to be cognizant of several factors related to its use.  First, this study was conducted over an 8-week period and data on the longer-term effects of this medication have not yet been published.  Second, because no direct comparison was made with stimulant medications, the efficacy of Atomoxetine in comparison to traditional stimulant medications is not known. Thus, there is no clear basis for determining whether this drug should be considered a first line treatment option for ADHD, or whether it should be used primarily for individuals who do not respond well to stimulants.

There were also several interesting and clinically relevant questions that could have been addressed in this report, but were not.  First, no analyses were reported in which children with the inattentive subtype of ADHD were considered separately.  This is unfortunate because it would be important to know whether Atomoxetine is equally effective on children with both the combined and inattentive subtypes of ADHD, especially since so little treatment research has been reported for the former.  Second, no separate analyses were reported for gender, leaving unknown the question of whether this medication is equally helpful for boys and girls.

Perhaps the biggest limitation to keep in mind, however, is the fact that many children treated with Atomoxetine are likely to remain highly symptomatic.  Recall that the average score on the ADHD-RS at the end of treatment was 1.5 standard deviations above the age-appropriate mean (i.e. in the top 7%) and only half of the participants were rated as showing no more than minimal symptoms on the CGI-S.  This is not meant to minimize the large number of participants that were helped significantly , but it does serve as an important reminder that no medication is equally effective for all children and the response of each individual child needs to be carefully monitored.

Assuming Atomoxetine receives FDA approval as expected, it will be a useful addition to the medical treatment options for children and adolescents with ADHD.  It remains to be seen, however, whether it will best be used as a first-line option or as an alternative for children who do not respond well to stimulants.  As with all currently available ADHD medications, however, it appears that many children will not benefit as much from this treatment as one would like, and that adjunctive treatments targeting residual difficulties will continue to be extremely important.

Although medication treatment for ADHD has been extensively studied, relatively little is known about how children and teens feel about taking medication.  This is an important gap since children's attitudes towards medication treatment, and their perception of how helpful it is, can have important implications for their willingness to continue this treatment for the necessary period of time.  Additional knowledge in this area could be especially helpful for dealing with conflicts about medication that often arise during adolescence.

A recent study provides interesting new information on this important issue (Moline, S., & Frankenberger, W. (2001). Use of stimulant medication for treatment of ADHD: A survey of middle and high school students' attitudes. Psychology in the Schools, 38, 569-584.)  Participants in this study were 651 students enrolled in 5 public schools from 4 districts in Wisconsin and Minnesota.  The average age of the participants was 15, suggesting that the majority were high school students (the breakdown of middle and high school students was not provided) and 78% of the participants were males.  (The authors provided no explanation for why males were over-represented in this study.)

All participants completed an initial anonymous survey that asked whether they were receiving medication for treating ADHD.  Forty students -- just over 6% of the sample, reported they were.  These students were then asked a series of questions that assessed their attitudes towards medication use. Questions focused on whether or not students wished to continue taking medication, how helpful they perceived it to be, and whether they experienced adverse side effects.  They were also asked whether peers had ever asked to buy, or be given, their meds.

Students not taking medication themselves were asked about their attitude towards peers receiving medication.  This is a nice addition to the study because very little information is available on whether peers have negative attitudes about classmates who take medication for ADHD.  Students were also asked whether they had observed students who take medication being approached by others to give away or sell their medication.

RESULTS

How do adolescents feel about taking stimulant medication for ADHD?

When asked "if it were up to you, would you stop taking your medicine?", 16 of the 40 students (35%) indicated they would.  A slightly greater number (n=20, 43%) indicated they wanted to continue taking meds.  Eleven students indicated that they were undecided.  Overall, 64% of the students either wished to continue their treatment with stimulants, or were at least not strongly opposed to continuing..

How helpful do adolescents perceive stimulant medication to be?

Questions focused on students' perception of medication benefits in 5 areas: academic achievement, behavior, getting along with peers, getting along with parents and teachers, and paying attention in school.  Examples of the questions asked in these areas are shown below.

"Has taking this medicine helped you become more organized at school?"

"Do you behave better at school when you take your medicine?"

"Is it harder or easier for you to make friends while on this medicine?"

"Do your parents like you more when you are on this medicine?"

"Does taking this medicine help you pay attention in school?"

Participants responded to each question on a 5-point scale, with higher scores indicating they perceived the medication to be helpful.  A response of 3 reflected a neutral attitude towards whether or not the medication helped.  Scores above 3 thus suggested that it was perceived as helpful; scores below 3 suggested that it was not perceived as helpful.

Results indicated that average scores for items pertaining to behavior, getting along with peers, getting along with parents/teachers, and paying attention in school were all greater than 3 (range 3.26-3.85).  On average, therefore, the adolescents perceived medication to be helpful in these areas.  For the academic achievement cluster, the average score was 2.95, which was significantly lower than results for all but one other cluster (i.e. getting along with peers).  Thus, participants felt that medication was less helpful to them with schoolwork than with the other areas. (Note: It is unfortunate that the authors did not report the percentage of teens that reported medication to be either helpful or not helpful in the different areas.  This would have enabled us to learn how many children perceive medication to be helpful as opposed to what was true for the group as a whole.)

A noteworthy finding is that the question for which medication received the greatest endorsement was one asking whether adolescents thought their parents liked them more when they were taking medication.  The average score on this question was the highest for any  question on the survey (i.e. 4.05 out of 5).  Apparently, these teens believed that taking medication had a major impact on how positively parents felt about them.

Do adolescents treated with medication experience adverse side effects?

Thirty percent of the students reported that they had experienced side effects from medication.  The side effect question that received the highest rating involved not feeling like eating lunch after taking medication. Overall, however, reports of perceived side effects were relatively mild.

Do adolescents get approached by others who want to buy, or be given, their medication?

Two-thirds of the participants reported that this had never happened to them; one-third reported this happens occasionally.  A small number -- about 10% of the sample -- indicated this was a frequent occurrence.  When asked who gave them their medication during the school day, 41% reported they took it themselves, 13% reported they received it from a school nurse, and 26% received it from a school secretary.  The remainder (20%)did not take medication at school.

How do peers view students being treated with medication for ADHD?

As noted above, participants not taking medication themselves (n=611) were asked how they felt about peers treated with stimulant medication.  Results from this part of the survey were quite positive.  The vast majority of students believed that students who took meds were not very different from other students, reported that they did not treat them differently, and noted that teachers did not treat these students differently.  When asked whether they felt taking medication had a significant impact on how students behaved at school, most felt that it did not.

Fifty-three percent of students reported that they had seen students who take medication being approached to sell it or give it away.  A significant minority --28% -- reported this was something they observed frequently.

SUMMARY AND IMPLICATIONS

Results from this study indicate that, among the adolescents in this sample, a slightly greater number would choose to continue taking medication than would choose to discontinue it.  Most students felt that medication helped them to pay attention, behave more appropriately, and get along better with peers, parents, and teachers.  They were less certain, however, that medication had a positive impact on their academic achievement.  This latter finding is interesting in that significant effects of medication treatment on long-term academic achievement have generally not been found. Apparently, adolescents' own perceptions are consistent with these other reports.

The results pertaining to peers' attitudes towards adolescents taking medication were encouraging.  There was no indication that peers hold negative attitudes towards adolescents taking meds, that they perceive them as "different", or that they treat them differently from anyone else. Because parents -- and children themselves -- are often concerned about the potentially stigmatizing effects of medication treatment, the fact that such effects were not evident in this study is a positive sign.

The most concerning results from this study pertain to the reports of adolescents being approached to sell/give away medication, as well as the reports from non-ADHD peers of observing such interactions.  Recall that about one-third of adolescents taking stimulant indicated they had experienced this.  In addition, over half of non-ADHD peers reported that they had seen this occur.  Although it is not possible to know how accurate these figures are, because the survey was completely anonymous, it seems unlikely that students were providing inflated estimates in order to convey a certain image.  If adolescents are really asked to sell their meds at anywhere near the frequency indicated by these results, it would be a major source of concern.

Such data would suggest that, although there is no evidence stimulant medication treatment increases the risk of illicit substance use (in fact, available evidence points to the contrary), it is possible that adolescents who take stimulants are at an increased risk of involvement in illicit transactions involving their medication.  If this is the case, then it seems extremely important that adolescents who take stimulant medication are made fully aware of the dangers involved in such transactions, and that they be fully prepared for how to respond if they are approached in this way.  In fact, if this is occurring as frequently as these data suggest, preparing adolescents to handle such experiences appropriately should be part of the treatment of every adolescent who receives stimulant medication.

In this regard, it is especially alarming that 41% of the teens reported they gave themselves their medication during the day, as opposed to receiving it from a nurse or other school staff member.  Because stimulants are classified as controlled substances, no public school that I am aware of would have a policy that allowed students to store and administer their own stimulant medication.  Is it possible that parents prefer to let their teenager manage his/her own medication at school rather than making the school responsible for this?  If so, this seems like a real problem.

(Note: One important benefit of longer-acting stimulants such as Concerta and Adderall XR is that in-school dosing is typically not required.  If meds are not taken at school, it should reduce the likelihood of an adolescent being asked to sell their medication. This could certainly still occur outside of school, however.  Because Atomoxetine, the new medication discussed in the article above, is a non-stimulant medication, adolescents not being treated with this medication should have little reason to want to take it.  This may be an important benefit of this new medication.)

This study has significant limitations, which the authors acknowledge, and which need to be kept in mind.  The most important limitation is that participants were from a limited geographic region and were in no way representative of the general population.  There is no way to know whether the results obtained for this sample accurately describe the experience of the larger population of adolescents with ADHD, or the attitudes that peers have towards classmates who are treated with meds.  It is also not possible to know whether the alarming reports about how often ADHD teens are approached for their meds, or the percentage who report administering their own meds at school, are representative of the larger population.

These limitations not withstanding, the authors have provided us with some very important findings that clearly indicate the need for more comprehensive study of these issues.  In future work, it will be important to learn more about why adolescents either do or do not wish to continue medication treatment, and the basis for their judgments about whether or not it is helpful.  As noted above, it will be especially important to learn how common it is for teens to self-administer their medication at school and what can be done to make sure this does not occur.  Finally, we need to know how often teens with ADHD are asked to sell or give away their meds, and what can be done to prevent them from becoming involved in such transactions.  These seem like absolutely critical questions for the field to address.