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Improving Long-term Efficacy and Effectiveness Outcomes in ADHD: A Treatment Development Workshop

Meeting Summary
Rockville, Maryland

Sponsored by:
National Institute of Mental Health
Division of Developmental Translational Research (DDTR)
Division of Services and Intervention Research (DSIR)

In March, 2007, NIMH sponsored a workshop to evaluate the current state of knowledge concerning long-term (i.e., adolescent and adult) efficacy and effectiveness outcomes in Attention Deficit/Hyperactivity Disorder (ADHD). The goal of the workshop was to identify research needs and opportunities for advancing treatments to improve functioning in adolescence and adulthood. Clinical and basic investigators with expertise in ADHD participated. Themes included the nature and predictors of ADHD-related impairments in adolescence and adulthood, treatment effectiveness, study designs for studying long-term outcomes, neurobiological models and mechanisms, and treatment development needs. Participants presented new research on novel treatment approaches, and discussions focused on research needs for improving functional outcomes. Other important aspects of treatment, such as long-term safety, were not the focus of this meeting. The following is a summary of the major themes discussed.

Major Themes

Listed below are some major themes and discussion points addressed during the workshop.

Long-term outcomes in ADHD

Despite the short-term effectiveness of current treatments for ADHD, particularly stimulant treatments, the limitations of these treatments for long-term outcomes are increasingly recognized. Among these limitations are failures to achieve long-term gains in academic achievement (e.g., elevated high school dropout rates) and limited vocational opportunities and success (e.g., frequent job changes, greater unemployment). The persistence of deficits in executive functions, motivational deficits, and impairments in self-regulation are increasingly acknowledged. Risk-taking behaviors associated with the adolescent period are associated with adverse health effects and high accident rates. Combined, these features put ADHD adolescents at risk for various other comorbidities (e.g., substance use/abuse), as well as for ill effects on health (e.g., high rates of nicotine addiction). Significantly impairing symptoms are now estimated to affect approximately 70 to 80% of adolescents with ADHD1 and 50% or more of adults with a history of ADHD2. Predictors of outcomes are multifactorial and complex. Specific outcomes have differing predictors and are themselves age-and possibly gender-specific.

Treatment effectiveness and limitations

A fairly broad choice of stimulant medications exists, as well as a nonstimulant, atomoxetine, for the treatment of ADHD. Increasingly, these medications are being prescribed for adults, but work is needed to optimize doses for this age group. In any case, treatment declines in adolescence, and compliance and adherence are significant issues in adolescents and adults. While symptomatic improvements are necessary for functional improvements, they may be insufficient for improving functioning. Greater emphasis on measurement of functioning, including social functioning, is needed. Many individuals with ADHD lack social and organizational skills, which may require adjunctive psychosocial treatments.

The best supported psychosocial treatments for children have involved contingency management/reinforcement approaches, parent training, and the integration of home- and school-based approaches. Limitations include the failure to maintain benefits post-treatment and to generalize to broader areas of life functioning. These may result from cognitive deficits, skill deficits, or performance deficits tied to the failures to self-organize and self-motivate behavior toward a later goal. Combined pharmacologic and psychological, i.e., multimodal treatments, can impact functioning over time, but follow up periods have been limited to childhood. Little research is available concerning the effects of psychosocial treatments on adolescent or adult outcomes.

Models and mechanisms

Neuropsychological research has demonstrated heterogeneity in the deficits associated with ADHD and has led to a multiple pathway model emphasizing executive dysfunction and motivational deficits involving the brain's reward system3. Brain imaging studies of adolescents and adults have implicated frontostriatal and frontoparietal neurocircuitry in ADHD4 . Preliminary studies comparing animal and human genes and behavior have identified common genetic predispositions that substantially increase the risk for ADHD.

Psychopharmacological investigations have traditionally focused on the dopamine pathways. Recent research is examining the noradrenergic, serotonergic, and cholinergic (e.g., nicotinic) neurotransmission and interactions among these systems. Experimental animal work is helping inform optimal dosing in humans. Rat studies show that low dose methylphenidate targets norepinephrine and dopamine neurotransmission preferentially within prefrontal cortex, providing a likely basis for enhancing cognition and calming behavior5.

Treatment development

Methodological needs

DSM-IV criteria are in many ways inappropriate for diagnosing ADHD in adolescents and adults. Revised diagnostic criteria and outcome measures that capture real world functioning are needed to advance treatment development. New statistical tools are being developed and translated from other fields to measure treatment response at both the individual and group levels. For example, growth mixture models allow researchers to compare baseline and treatment responses for subgroups based on their characteristics (e.g., aggression), as well as interaction effects (e.g., of psychosocial and pharmacologic treatments).

Novel approaches

Pharmacology: Looking beyond the role of dopamine in therapeutic responses may expand our range of treatment targets to include, for example, noradrenergic, serotonergic, glutamatergic, muscarinic, nicotinic, and GABAergic receptors. Another novel approach may be to combine efficacious treatments. For example, combining agonism that is more dopaminergic with agonism that is more adrenergic might yield superior symptomatic improvement.

Genetics: The identification of genes that underlie treatment variability may be a more tractable problem than the genetics of the pathophysiology of ADHD. Genetics studies may help predict individual responses to medications and psychosocial treatments and adverse events (e.g., abnormal movements, irritability), as well as potentially contribute to the prevention of comorbidity, such as that with depression.

School-based treatments for adolescents: New efforts to address adolescent needs that impact school performance are targeting organizational skills for school-related (e.g., homework management) and other domains (e.g., social skills). Checklists are used for monitoring progress and for use by counselors and parents in implementing contingencies. Social skills are approached by helping students meet their own social goals and interpret context using coaching and skills groups.

Organizational skills training: New research is testing the efficacy of adjunctive organizational skills training for elementary school children with an eye toward preparing them for the greater independence associated with the adolescent period. Treatments teaching organization, time management, and planning skills in ecologically-relevant contexts are being evaluated.

ADHD-specific cognitive-behavioral therapy: Using patient input, researchers are developing a comprehensive, ADHD-specific cognitive-behavioral intervention targeted toward improving functioning in adults and facilitating generalization to all life domains. Treatment modules, developed to address the problems most frequently reported by patients, are addressing organizational skills (e.g., use of a task list and calendar), planning, coping with distractibility, and cognitive restructuring to help with associated anxiety and depression.

Cognitive training: Cognitive training seeks to improve a specific cognitive skill, such as attention or working memory, by beginning with a relatively easy task and gradually increasing the complexity and difficulty level, similar to interventions used in the head injury literature. Recent efforts employing computerized training with children have begun to show promise in improving behavior, e.g., ability to complete assignments. However, effect sizes are modest and greater evidence of generalization is needed.

Conclusions

Research over the past 30 years has improved our understanding of ADHD as a life-long condition. We now have both pharmacologic and psychosocial treatments with proven efficacy. Nonetheless, while these treatments are quite effective in controlling symptoms, there is substantial room for further advances. Despite treatment, many adolescents and adults with ADHD remain substantially impaired in their daily functioning. A significant public health need exists to develop better treatment interventions for adolescents and adults with a special focus on promoting competence and improving functioning.

References

1. Barkley, RA, Fischer, M., Smallish, L., Fletcher, K. (2002). The persistence of Attention-Deficit/Hyperactivity Disorder into young adulthood as a function of reporting source and definition of disorder. Journal of Abnormal Psychology. 111 (2), 279-289.

2. Fischer, M., Barkley, R.A., Smallish, L., Fletcher, K. (2005). Executive function in hyperactive children as young adults: attention, inhibition, response perseveration, and the impact of comorbidity. Developmental Neuropsychology. 27 (1), 107-133.

3. Castellanos, F.X., Songuna-Burke, E.J.S., Milham, M.P., Tannock, R. (2006). Characterizing cognition in ADHD: beyond executive dysfunction. TRENDS in Cognitive Sciences. 10 (3), 117-123.

4. Bush, G., Valera, E.M., Seidman, L.J. (2005). Functional neuroimaging of Attention-Deficit/Hyperactivity Disorder: a review and suggested future directions. Biological Psychiatry. 57, 1273-1284.

5. Berridge, C.W., Devilbiss, D.M., Andrzejewski, M.E., Arnsten, A.F.T., Kelley, A.E., Schmeichel, B., Hamilton, C., Spencer, R.C. (2006). Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biological Psychiatry. 60, 1111-1120.