As predicted, individuals with ASD and ADHD had a higher prevalence of any medication use and a greater proportion of individuals taking multiple medications relative to youths with ASD or ADHD alone. Almost 6 in 10 youths in this group were taking at least one medication, and the majority of youths were taking more than one medication. Also striking are the high rates of antipsychotic, antidepressant/antianxiety, and stimulant medication use in these youths. Observations from the present study reinforce the complexity of pharmacologic treatment of challenging behavior in youths with ASD and ADHD and underscore the need to identify efficacious medication algorithms for this population.
Individuals with ASD-only were least likely to take any medication, but when they did use a medication, they often used more than one. Individuals with ASD-only showed a diverse medication profile, with large proportions taking an antipsychotic or antidepressant/antianxiety medication. In contrast, adolescents with ADHD-only were more likely to use only a single medication, often a stimulant medication as would be expected per current practice parameters. The high prevalence of any medication use in youths with ADHD-only (49.0%) underscores the effectiveness of stimulant medication and the existence of clear practice parameters guiding ADHD medication treatment (American Academy of Child and Adolescent Psychiatry 2002
). It is likely that the diverse array of observed medication usage and the substantial prevalence of poly-pharmacy in individuals with ASD are at least partly due to the current trial-and-error treatment approach focusing on associated behavioral disturbances. Clearly, additional efficacy and effectiveness studies examining the treatment of core and associated ASD symptoms are needed to guide pharmacologic treatment of these youths. This is particularly important given the added side effect burden often present with poly-pharmacy and the possibility that individuals with ASD may not be fully able to communicate about side effects.
FDA approval of antipsychotic medications for the treatment of irritability or aggression in youths with ASD has likely increased use of these medicines in adolescents with and without ADHD symptoms. To date, we are not aware of any studies that have specifically examined the efficacy of these medications separately in individuals with and without ADHD. Given the recognized heterogeneity of ASD (Hus et al. 2007
), this will be an important next step. Additionally, few studies have moved beyond efficacy to examine the effectiveness of antipsychotic medications in individuals with ASD with or without ADHD. The potential for significant weight gain and metabolic syndrome further reinforces the need for longer-term effectiveness studies that also evaluate long-term side effect profiles in ASD groups. These effectiveness studies may initially focus on populations examined in the efficacy studies, but this may allow secondary analyses to examine whether these medications are also effective for treating ADHD-like behaviors in ASD-affected youths. Recently, our group identified that antipsychotic medications augment the effectiveness of intensive behavior management in youths who showed only minimal response to medication alone (Aman et al. 2009
; Frazier et al. 2010
). Combination effectiveness studies, analogous to those done in youths with ADHD, will be crucial for identifying the most effective treatment regimens for sub-groups of individuals with ASD.
The present estimates of medication use are similar to estimates from other medication surveys of individuals with ASD (Martin et al. 1999
; Aman et al. 2005
; Mandell et al. 2008
; Rosenberg et al. 2009
). The use of a nationally representative sample of adolescents with ASD-only and ASD+ADHD confirms the high rates of medication use in these youths. Consistent with previous studies, we identified nontrivial rates of mood stabilizer and stimulant use in individuals with ASD (Aman et al. 2005
; Hellings et al. 2005
; Research Units on Pediatric Psychopharmacology Autism Network 2005
; Rosenberg et al. 2009
). Careful studies of the efficacy and effectiveness of these medication classes, which have been less well studied than antipsychotics and SSRIs, are needed. In particular, the present results suggest that future studies examining these medication classes may consider focusing on individuals with both ASD and ADHD, as these youths appear to represent a sub-group with distinct and intense psychopharmacologic needs.
Two need factors, greater externalizing behavior and lower functional ability, significantly predicted medication use in the ASD-only group and approached significance in the ASD+ADHD group. Contrary to expectation, predisposing and enabling factors were generally unrelated to medication use across all groups. The most notable exception to this pattern was lower medication use in African American (both ASD groups) youths. This finding is consistent with previous results (Mandell et al. 2008
) and suggests that race may be an important moderator of access to psychiatric services. Interestingly, adolescents with ADHD-only did not show this pattern. There are several possibilities for this difference, including greater historical awareness of the ADHD diagnosis relative to the recent recognition of ASD, heavy reliance on teacher report in identifying ADHD (Vaughn et al. 1997
; Wolraich et al. 2003
), and the widespread availability of effective ADHD medication treatments. Regardless, lower medication use in African American youths suggests that they are currently underserved, and interventions targeting these populations and the physicians who serve them are warranted.
The primary limitations of this study were the reliance on caregiver report and special education designations in obtaining diagnostic classifications, caregiver report of medication use, lack of information concerning other ASD-associated co-morbidities, and the cross-sectional nature of the design. Caregiver report of a clinical ADHD diagnosis is sub-optimal because this combination is not actually permitted by DSM-IV, although it is often used in clinical practice to increase the likelihood of appropriate treatment. Thus, the ADHD diagnosis should be viewed as a proxy for the clinical observation of co-occurring ADHD symptoms in individuals with ASD. Use of caregiver report and special education classifications for obtaining ASD diagnosis is also clearly inferior to using direct assessment or semi-structured psychiatric interviews to derive clinical diagnoses. Fortunately, this design weakness is likely to under-estimate rather than over-estimate group differences in medication use. This is because caregiver-reported ADHD and ASD education classifications may result in misclassifications that reduce the purity of these groups. Thus, it is likely that significant group differences are an accurate reflection of medication use across these conditions, but that nonsignificant results may be due to classification error or reflect true equivalency.
Caregiver report of medication use, while less ideal than direct monitoring of medication, permitted national sampling of ASD-affected youths—a primary strength of this study. The cross-sectional nature of the design limits conclusions regarding the use of medication over time. Some studies have suggested increases over time in the rates of psychotropic medication use in ASD, particularly for antidepressants and antipsychotics (Aman et al. 2005
; Esbensen et al. 2009
). Additional waves of data from this study will be helpful for examining factors influencing the onset of new psychotropic medication use. These studies will substantially add to existing knowledge of medication use in ASD because most previous studies, including the present study, have only focused on any current medication use.
Importantly, analysis of demographic differences across study groups suggested a misclassification bias affecting the identification of ASD. This bias indicates that some individuals who likely have ASD were misclassified as having ADHD-only or other conditions. Specifically, youths from rural regions, with less educated caregivers, and who had public/nonprivate insurance were less likely to receive an ASD diagnosis relative to an ADHD diagnosis. Fortunately, this misclassification bias should serve to reduce group differences, resulting in an under-estimate of effects. The implications of this bias are that nonsignificant findings may simply be due to misclassification of ASD and ADHD groups rather than truly non-significant results. Coupling this bias with reduced classification precision (resulting from the use of caregiver reports of ADHD and educational classifications of ASD instead of clinical psychiatric diagnoses) suggests that significant results are likely to be of even greater magnitude than estimated by the present study.