DO COMORBID CONDITIONS IMPACT HOW CHILDREN WITH ADHD RESPOND TO TREATMENT?

Many of you are already familiar with the results of the MTA study, the largest treatment study of ADHD every conducted.  The goal of this study was to compare the effectiveness of carefully conducted medication treatment, intensive behavioral treatment, the combination of medication and behavioral treatment, and typical treatment for ADHD as practiced in community. Participants in this study were 579 children between the ages of 7 and 9.9 who had been carefully diagnosed with ADHD, Combined Type.  Although children in all 4 treatment groups showed significant improvement, those in the medication-only group and the combined-treatment group had significantly greater improvement in their core ADHD symptoms than children given only intensive behavioral treatment or community care.  There was also evidence that combined treatment provided a modest incremental benefit compared to careful medication treatment alone.

An important question not fully addressed in the initial analyses of the MTA results is whether treatment response may vary as a function of the other conditions a child may have in addition to ADHD (i.e. comorbid conditions). Unfortunately, it is well known that children with ADHD often have other conditions as well, including Oppositional Defiant Disorder (ODD), Conduct Disorder (CD), mood disorders, and anxiety disorders.

These comorbid conditions can complicate a child's treatment and tend to be associated with a poorer long-term prognosis.  Therefore, it is very important to carefully examine whether the presence of these other difficulties affects the type of impairments that children have, how they respond to treatment, and the type of treatment that is likely to be most helpful. (Note: In the MTA study, medication and behavioral treatment were the only ones investigated because they are the interventions with the strongest empirical support at this time.)

These important question were examined in a recently published study titled "ADHD comorbidity findings from the MTA study: Comparing comorbid subgroups" (Jensen et al., (2001). Journal of the American Academy of Child and Adolescent Psychiatry, 40, 147-158).

In this report, the authors compared the treatment outcomes for 4 different groups of children from the MTS study: children with ADHD alone (n=184), children with ADHD and either ODD or CD but without an anxiety disorder (n=171), children with ADHD and an anxiety disorder but without ODD or CD (n=81), and children with ADHD, ODD/CD, and an anxiety disorder (n=143). (Note: Some of the children diagnosed with anxiety disorders had mood disorders as well.)  Diagnoses and assignment to the different groups were based on structured psychiatric interviews conducted with parents, and thus do not reflect children's own reports of fears, worries, and other symptoms of anxiety.

Results

A number of different baseline and outcome measures were collected in this study, including core symptoms of ADHD, oppositional/aggressive behavior, academic achievement, anxiety and depression symptoms, social skills, and parent-child relations.  Although the results varied across these different measures, there are several important general conclusions that can be made.

*       Parents of children with ADHD and ODD/CD report greater difficulty with their child than parents of children with ADHD and an anxiety disorder.

        An important exception to this general pattern is that children with ADHD and an anxiety disorder were more likely to have academic problems and to be diagnosed with a learning disability.

*       Overall, children with ADHD and an anxiety disorder tended to be more treatment responsive than children with ADHD alone or children with ADHD and ODD/CD

        Children with ADHD and an anxiety disorder showed a positive response to all 3 MTA treatments (i.e. medication only, behavior therapy only, and combined treatment) and tended to show greater improvement than children in the other groups.  Thus, although children in the other groups also showed important benefits from treatment, the treatment gains for children with ADHD and an anxiety disorder tended to be slightly greater.

*       Behavioral interventions were particularly likely to be helpful for children with ADHD and an anxiety disorder.

        On a number of specific outcome measures - including measures of academic achievement - as well as an overall composite measurement of outcome, children with ADHD and anxiety were more likely to show a positive response to behavioral treatment than were children in the other groups. Unlike the children in the other groups, these children did as well with behavior therapy alone as they did with medication alone.

*       For children with ADHD only, or ADHD and ODD/CD, treatments with medication seem especially effective, while behavioral treatment alone may be less effective.

        Children with ADHD alone or ADHD and ODD/CD showed relatively little response to intensive behavioral therapy only.  The use of carefully conducted medication treatment thus seems especially important for these types of ADHD children.

*       For ADHD children who also have both an anxiety disorder and ODD/CD, the use of combined treatment (i.e. medication and behavior therapy) may offer substantial advantages.

For these children with the most complex set of symptoms, overall outcome for combined treatment was significantly better than for either behavioral treatment or medication treatment alone.

Summary and Implications

These findings add substantially to the main results of the MTA study and have clinical implications that are potentially important for parents and clinicians.  First, it appears that children with ADHD and a comorbid anxiety disorder may be especially likely to have concurrent academic problems and learning disabilities.  Thus, for these children, it would be especially important for this possibility to be carefully considered and investigated.  Although this is likely to occur in a comprehensive evaluation conducted by a child mental health specialist, this may be short-changed because of insurance-imposed limitations.  In addition, primary care physicians may not always have the training that enables a careful assessment of academic functioning and learning difficulties to be completed.

Second, for children with ADHD and an anxiety disorder, carefully executed behavioral treatment may yield treatment gains that are equivalent to what would be provided by medication.  Thus, in situations where parents have strong concerns about the use of medication, where children do not benefit from it, or, cannot tolerate it, behavioral treatment alone can be a reasonable treatment choice for these children.  For these children, beginning treatment with behavior therapy alone and carefully monitoring their progress may alleviate the need for medication in many instances.

Third, parents and clinicians should be aware that in children with ADHD alone, or ADHD  with ODD/CD, the use of carefully conducted medication therapy is likely to be especially critical.  In the MTA study, these children did not respond well to medication treatment alone even though they showed robust responses to medication.  When an anxiety disorder is also present, however, the addition of behavior treatment may confer some important incremental benefits.

As with any study, there are several important caveats to keep in mind. First, these results apply specifically to children with the combined subtype of ADHD between the ages of 7 and 10.  The extent to which they would generalize to children with other ADHD subtypes (i.e. inattentive or hyperactive-impulsive) and of different ages is unknown.  Second, there are always individual exceptions to results that are derived from comparing groups.  Thus, although these results indicate what is more likely to be true about a specific child (e.g. a child with ADHD alone is likely to respond better to medication treatment than to behavioral treatment), there are always exceptions at the individual level.

Most importantly, the results from the MTA study are based on both medication and behavioral treatment that can be considered state-of-the-art. For example, children receiving medication treatment began with a careful placebo-controlled trial to determine their optimum starting dose, and were then carefully monitored each month to determine when modifications to dosage or even type of medication were necessary.  Behavioral treatment included extensive work with parents, an 8-week summer program for children, and an intensive behavior management system at school.

Unfortunately, this is not the type of medication treatment or behavioral treatment that is typically provided in community settings.   In fact, one of the main findings of the MTA study is that children receiving medication treatment or combined treatment in the study did significantly better than those whose treatment occurred in the community.  Thus, one cannot assume, for example, that the behavior treatment most children have access to would show the same positive impact on children with ADHD and an anxiety disorder that was shown in this study.

Rather than being discouraged by this possibility, however, it is important for parents to learn as much as they can about what these state-of-the-art MTA treatments entailed, and to do their best to make sure that the treatment received by their child matches this to the extent possible.  With medication treatment, for example, even though the entire placebo-controlled procedure would be hard to follow exactly, it is quite possible to incorporate several important elements of this procedure, including testing a child on a full range of doses, obtaining systematic feedback from teachers on the child's behavior and school work on each dose, and obtaining such feedback on a regular basis to determine when treatment modifications may be necessary.  These simple steps can make an important difference.

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The Journal of Attention Disorders recently published a special issue in which the results of a large-scale survey conducted with ADHD experts from medical and psychology backgrounds were reported.  The goal of this survey was to establish guidelines that address important clinical issues for which there may currently be little controlled scientific evidence, but for which there exists considerable experience in clinical practice.  By obtaining and summarizing the opinions of a large number of experts (i.e. 44 physicians and 47 psychologists, representing 86% and 94% of the individuals to whom a survey was sent), the results create a set of guidelines that can be informative to both parents and practitioners.

As noted above, the survey was designed to obtain and synthesize expert opinion on issues that are not yet fully addressed in the research literature on ADHD.  The designers of the survey were themselves recognized ADHD experts (Keith Conners is the lead author) and are careful to note that because individuals with ADHD can vary so widely along multiple dimensions, the consensus recommendations will certainly not be appropriate in all circumstances.  They are also careful to note that the survey was financially sponsored by the pharmaceutical industry, and describe the steps taken to avoid having this bias the results.  The major effort here was to present data from every respondent so that readers can compare the summary guidelines with the raw data on which each guideline is based.

It is also noted appropriately that the guidelines represent current expert opinion, and that expert opinion at any given time can be revealed by future studies to be wrong.  For example, future studies may indicate that treatments currently regarded as "alternative", and thus not generally recommended, are actually quite helpful in many cases and should be considered to be important treatment options.  The important point here is that any set of recommendations can only be based on the best available evidence, and should this evidence change over time, so will the recommendations.

Survey results were summarized to produce guidelines in multiple areas, including the assessment and treatment of ADHD, how these vary depending on the type of ADHD (i.e. combined, inattentive, or hyperactive-impulsive), and the age of the client.  Particular attention is given to important clinical issues such as what to do when treatment is only partially effective or even ineffective, what constitutes adequate monitoring, and how the current state of treatment for ADHD can be improved.  Reviewing the entire set of guidelines is beyond the scope of what can be presented here, and the focus in this issue will be on three particular points -- selecting an initial treatment strategy, changing the treatment regimen when response is judged to be inadequate, and what constitutes appropriate ongoing care.  In future issues of Attention Research Update, additional guidelines from this report may be presented.

Selecting an initial treatment strategy

The question facing the experts here was how to sequence the treatments for ADHD -- whether to begin with medication alone, psychosocial treatment alone, or a combination of both from the start.  Experts were told to assume that both types of treatment would be available, and to rank order their recommendations in terms from most to least preferred option.  It is reasonable to assume that by psychosocial treatment, the experts were referring to the types of non-medical interventions for ADHD for which empirical support has been shown, including parent training, clinical behavior therapy, skills-based training, psycho-educational interventions, etc.

Psychosocial treatment alone

Starting with psychosocial treatments alone was the consensus recommendation in situations where ADHD symptoms were judged to be mild and/or when the child was of preschool age.  In cases where there was a co-occurring internalizing problem (i.e. mood or anxiety disorder), beginning with a psychosocial intervention alone and beginning with a combination of medication and psychosocial treatment were rated equivalently.

Medication treatment alone

Beginning with medication treatment alone was never the clearly preferred option among this expert group.  It was regarded as equally appropriate to beginning with combined treatments, however, for more severe cases of ADHD, for individuals with the combined or hyperactive-impulsive subtypes, and for adults.

Combined treatments

Situations where combined treatment was viewed as an equally appropriate initial treatment strategy to medication or psychosocial intervention alone are described above.  In addition, combined treatment was regarded as the best initial option for individuals with the predominantly inattentive subtype of ADHD, for children and adolescents, and/or when there are co-occurring behavior disorders (i.e. Oppositional Defiant Disorder or Conduct Disorder).

The consensus opinion of these experts thus shows a strong preference for combined treatment.  For children and adolescents, this would be the preferred option except in cases where symptoms were judged to be mild (i.e. psychosocial treatment alone would be reasonable here), or when there is a strong preference for one treatment approach vs. the other.  The preference for combined treatment is consistent with MTA study results in which the researchers found a modest, but statistically significant, advantage for combined treatments over medication alone for several specific outcomes and for an overall composite of the different outcomes considered.

Changing the treatment regimen

An issue closely related to the choice of initial treatment strategy is the appropriate time to change treatment regimens when the response has been inadequate.  Several factors were deemed important to evaluate before making any such change.  Before making changes to medication treatment, the following steps were advised:

*       Ensure adequate dosage - In many instances, patients may be receiving a dosage that is too low to provide maximum benefit, and adjusting the dose can yield significant additional benefits.  This often occurs when researchers do not test a full range of during an initial trial, but instead use the first dose on which some improvements are evident as the maintenance dose.

*       Evaluate for compliance problems - Being certain that medication is actually being taken as instructed is necessary before changing medications or deciding medication will not provide important benefits.

*       Ensure coverage across waking hours - It is important to make sure the type of medication and/or dosing schedule provides adequate coverage across the period of time when symptom management is critical.  (Note: Now that medications with longer durations have become available -- e.g. Concerta -- this may be easier to ensure than when multiple daily doses are required as with regular methylphenidate.)

In regards to switching medications when a positive response to the initial medication choice is not obtained, the panel strongly recommended that several different stimulants be given a thorough trial before trying a different class of medication (e.g. switching to an anti-depressant). Adding new meds rather than trying another type of stimulant first was also not a preferred option.

In cases where medication alone has been used to begin treatment, the consensus was that psychosocial treatment should be added when no response has been noted over a 5-week period of careful trials.  In situations where only a partial response (i.e. some symptoms clearly remain and impair functioning), it was recommended that psychosocial interventions be added after 7 weeks.  When psychosocial treatment alone has been the initial strategy, the experts advised adding medication when a month has elapsed with no response, and waiting between 6-7 weeks when at least a partial response has been obtained.

What is an appropriate level of maintenance care?

One of the real drawbacks in the care that many children with ADHD receive is the lack of adequate monitoring and follow-up.  In addition, those receiving medication often stop taking it prematurely.  The guidelines in this section are thus especially important to note.

For children/adolescents who respond well to medication, it is suggested that medication be maintained on the dosage determined to be most effective for 1-2 years before trying to taper it.  A typical duration of medication treatment for good responders ranged from 2-10 years.  For adults, it was recommended that those showing an excellent medication response continue to take it for 2-5 years before trying to taper or discontinue.

For individuals who have had an excellent response to medication treatment (i.e. symptoms have been fully normalized with no residual impairment), it was advised that follow-up visits be scheduled every 3 months.  In cases where only partial response has been obtained, the consensus opinion called for monthly visits.  Thus, ongoing monitoring of treatment response is seen as essential.

For psychosocial interventions, weekly visits are recommended during the first 6 months of treatment.  A range of 7-20 visits would be held during this period depending on response.  This figure is for an "uncomplicated ADHD patient", and would need to be increased when difficulties were more pronounced than is typical.

6-12 months after treatment has been initiated, booster sessions were recommended to be held every 1-3 months once symptoms have been fully normalized, and 1-2 times each month when there has been only a partial response.  Sessions for ongoing monitoring beyond 12 months should take place 1 to 2 times per year for children and adolescents, and as needed for adults.

Summary

The recommendations above are important in that they reflect the most widely held views among a large number of experts.  As noted above, these guidelines will not apply to every individual, and treatment decisions for specific individuals can be influenced by a wide variety of factors that no set of guidelines can fully capture.  In cases where treatment choices fall clearly outside of these guidelines, however, it would be important to be able to specify the factors that have resulted in what would be considered atypical recommendations.