Economic implications of attention-deficit hyperactivity disorder for healthcare systems
Attention-deficit hyperactivity disorder (ADHD) is one of the most common chronic conditions of childhood, with adverse consequences that persist through adolescence into adulthood. Thus, the burden of illness associated with ADHD is high for affected individuals, their families, and society at large. This article reviews available information about ADHD-associated utilisation of healthcare resources, direct medical costs, and the costs or cost effectiveness of pharmacological interventions.
Published estimates suggest that direct medical costs for youth with ADHD are approximately double those for youth without ADHD. Cross-sectional studies suggest that ADHD-associated incremental costs are highest for mental health services and pharmaceutical costs, and are greatest for youth with comorbid psychiatric conditions and for those being treated with stimulant medication. To guide relevant clinical and health policy, additional research is warranted on the following: source of increased costs observed among persons with ADHD; patient characteristics of those accruing high medical costs; and the long-term effect of ADHD treatment on direct and indirect costs.
Attention-deficit hyperactivity disorder (ADHD) has been described as both the most studied mental diagnosis and the most controversial. It is one of the most common chronic conditions of childhood, with population-based prevalence rates ranging from 3% to 19%.[2, 3, 4, 5, 6, 7, 8, 9] The variability in estimates reflects across-study differences in the method of case ascertainment, as well as differences in the geographic regions, calendar years, lengths of observation, and age ranges under study. It is well documented that the core symptoms of ADHD (developmentally inappropriate inattention, hyperactivity, and impulsivity) contribute to adverse academic and social functioning[10, 11, 12, 13, 14, 15, 16, 17] and that the negative consequences of ADHD with respect to such functioning persist throughout adolescence into adulthood.[18, 19, 20, 21, 22, 23, 24, 25, 26] It is also recognised that the prevalence of certain medical conditions is increased for children and adolescents with ADHD. Compared with their peers without ADHD, youth with ADHD exhibit higher levels of psychiatric comorbidity,[11,14,27, 28, 29, 30] and are at increased risk of accidents, severe injuries, and other chronic health conditions.[15,31, 32, 33, 34, 35]
In recent years, researchers have begun to focus on medical care costs associated with ADHD. This article reviews available information on rates of medical care utilisation and direct medical costs associated with ADHD and the cost effectiveness of pharmacological treatment. The emphasis is on population-based studies of school-aged subjects. The comparison of published estimates of ADHD-associated utilisation and costs provides insight into the medical burden of ADHD and informs efforts by researchers as well as clinical and health policy decision makers to reduce that burden.
1. Method of Literature Search
2. Attention-Deficit Hyperactivity Disorder-Related Medical Utilisation
2.1 Office Visits and Mental Health Service Use
Population-based surveys of physicians who treat children and adolescents reveal that both the rate and the proportion of office visits associated with ADHD are high and have increased dramatically over the past decade (see tables I and II). Using data from the Child Behavior Study (CBS), Kelleher et al. reported that clinician-identified attentional problems accounted for 9.2% of all visits in 1996, up from 1.4% in a similar study conducted in 1979.
Temporal trends in the rate of office visits in the US are available from the National Ambulatory Medical Care Survey (NAMCS), a representative sample of all ambulatory office visits to physicians who engage in office-based patient care. The survey obtains information on symptoms, diagnoses and medications for a random sample of visits occurring in a 7-day period, as recorded by a physician or their staff. The most recent NAMCS study of ADHD-related visits among persons aged 5–18 years used data from sequential surveys conducted in 1990 through 1998. The authors estimated that 5.9% of US residents in this age group had an office visit for which there was a documented diagnosis of ADHD in 1998, a 3-fold increase from 1.9% in 1990. However, despite the high rates of use, Hoagwood et al., in an examination of 1996 US NAMCS data for persons aged 0–17 years, observed that 25% of ADHD-coded office visits had no recommendation for follow-up care. The authors noted that the absence of follow-up for youth diagnosed with ADHD was inconsistent with National Institutes of Health consensus panel guidelines and association-issued practice parameters.
Youth with ADHD account for an even higher proportion of mental health visits. US data from NAMCS studies reveal that 60% of all office visits for mental health problems by youth in 1996 were associated with a diagnosis of ADHD, and that 25% of ADHD office visits between 1989 and 1996 were conducted by a psychiatrist. Estimates of the proportion of mental health services in the general health sector that were used by children and adolescents with ADHD in the US have also been obtained using the MarketScan database, a collection of inpatient and outpatient healthcare claims for a national sample of over 7 million privately insured individuals. The study sample consisted of all individuals aged ≤17 years with a claim for mental health services in 1996 (n = 139 806). The authors found that 30.1% of such services were associated with a diagnosis of hyperactivity.
High use of mental health services by US children with ADHD was also evidenced with data from the CBS. Rushton et al. reported that 4012 (19%) of the youth recruited during office visits to paediatricians and family practitioners had one or more clinician-identified psychosocial problems at the initial visit. Of the 4012 with any psychosocial problem, 50% were identified as having ADHD. Importantly, however, among all youth with a psychosocial problem who were referred for mental health services, those with ADHD accounted for only 21% of all such referrals. Thus, although youth with ADHD accounted for a large proportion of mental health referrals, the rate of such referrals was lower for ADHD than for most other psychosocial problems. The CBS findings are compatible with results of the 1996 NAMCS study by Hoagwood et al. in which it was observed that less than 40% of office visits by persons aged 0–17 years with a discharge diagnosis of ADHD involved mental health counselling and only 25% involved psychotherapy, a decline from 40% in 1989. The latter decline parallels dramatic reductions in the proportion of total US healthcare dollars that were dedicated to psychiatric and mental healthcare over this time period.[52,57,58]
The high rate of office visits and mental health service use associated with ADHD as evidenced from physician surveys is reinforced by population-based studies comparing medical care utilisation between persons with and without ADHD. Guevara et al. conducted such a comparison using administrative data from a large health maintenance organisation (HMO) in western Washington State, USA. The study was limited to youth aged 3–17 years in 1997 who were continuously enrolled and who used services in that year. Of the 57 216 youth identified, 2992 (5.2%) were defined as having ADHD based on the presence of any discharge diagnosis code for ADHD and/or a pharmacy fill for a stimulant medication. Of those identified as having ADHD, 28.7% also had a diagnosis of a coexisting mental health disorder compared with only 3.8% of those without ADHD. Between-group comparisons of the proportions with a discharge diagnosis code for one or more of a few selected other medical conditions (e.g. asthma, diabetes mellitus, epilepsy) revealed less variation (35% of ADHD cases vs 31% of controls). Compared to youth without ADHD, those with ADHD were both more likely to use primary care (Odds ratio [OR] = 1.5, 95% CI = 1.2–1.9) and to have more frequent primary care visits (mean ± SD = 3.8 ± 3.3 vs 2.4 ± 1.6; p < 0.001). The likelihood of an outpatient mental health visit was markedly increased for youth with ADHD compared with those without ADHD (OR = 9.0, 95% CI = 7.5–10.9), as was the frequency of such visits (mean ± SD = 1.4 ± 3.1 vs 0.1 ± 1.0; p < 0.001).
Pastor and Reuben also compared medical care utilisation between youth with and without ADHD, using data from the National Health Interview Survey (NHIS), a nationally representative telephone survey in which household informants are identified and queried about sociodemographic characteristics, health conditions and healthcare use of family members. Pastor and Reuben used the revised 1997–1999 NHIS and focused on children aged 6–11 years. By age 10–11 years, 11.5% of boys and 4.8% of girls had been told by a physician or healthcare professional that they had ADHD. Compared with children with no such diagnosis, those with a diagnosis had more informant-reported health conditions and were more likely to have visited each of the following provider types in the prior year: paediatrician or primary care physician (88% vs 76%), mental health professional (42% vs 4%), specialist physician (23% vs 10%), therapist (occupational, speech, etc.) [16% vs 5%], and an eye doctor (29% vs 20%). Between-group differences in service use were reduced when the analysis excluded persons with other health conditions, but healthcare use by children with a diagnosis of ADHD remained significantly higher.
A similar study by Chan et al. used data from the 1996 Medical Expenditure Panel Survey (MEPS). The MEPS is a nationally representative household telephone survey, with potential subjects drawn from a sub-sample of households that participated in the prior year’s NHIS. As with the NHIS, the MEPS used computer-assisted queries to obtain information from a household informant on the health status of each family member. In the MEPS, information on healthcare utilisation for each family member is supplemented by information from informant-identified medical providers and payors. Chan et al. used 1996 MEPS data to identify individuals aged 5–20 years with informant-reported ADHD, asthma, or neither condition. Persons with at least two prescriptions for psychostimulant medications were also considered as having ADHD. Of the 5439 individuals aged 5–20 years in the study, 165 (3.0%, representative of 3.5% nationally) were identified with ADHD, a rate lower than the cumulative incidence of ADHD in children aged 10–11 years in the revised 1997–1999 NHIS, reported by Pastor and Reuben (discussed previously in this section). Of those youth with informant-reported ADHD, 4.2% were reported as having fair or poor physical health and 13% were reported as having fair or poor mental health. These percentages were reversed for youth with asthma (13% and 4.3%, respectively), and lowest for youth with neither ADHD nor asthma (2.4% and 2.6%, respectively). Youth with ADHD experienced significantly more outpatient visits (including mental health visits) [mean ± standard error of the mean (SEM) = 6.0 ± 0.6] compared with both youth with asthma (4.3 ± 0.4; p = 0.03) and youth with neither condition (2.4 ± 0.1; p < 0.001). In an analysis limited to youth with ADHD, Chan et al. observed that those with a prescription for stimulant medication during the year had twice the number of outpatient visits as those with no such prescription (mean ± SEM = 7.2 ± 0.8 vs 3.5 ± 0.7; p = 0.002).
Two additional population-based studies comparing medical care utilisation for youth with and without ADHD focused on specific subgroups. Bussing et al. obtained data on children in a county of North Florida, USA who were enrolled in special education programs. The parents of all second, third and fourth grade students were invited to participate in a telephone survey that included two ADHD screening tools. The parents of 499 (69%) of the children completed the survey. Compared with children who scored in the normal range on either screening measure, those who scored in the clinical range for ADHD had more physician visits in the prior 12 months (mean ± SD = 4.1 ± 4.3 vs 2.5 ± 3.5; p < 0.001) and approximately twice the rate of contact with a mental health professional (49% vs 25%; p < 0.001) or primary care provider for treatment of mental health conditions (35% vs 16%; p < 0.01). Investigation of characteristics associated with healthcare use revealed utilisation was higher for boys than for girls, for students with no comorbid learning disability compared with those with comorbid learning disability, for insured students compared with those with no insurance, and for students from families of high compared with low socioeconomic status.
Similar high rates of medical utilisation associated with ADHD were observed in a study of Medicaid-insured youth by Kelleher et al. The study sample consisted of individuals aged 7–20 years from Pittsburgh, USA and seven surrounding counties who were continuously enrolled in Medicaid during the fiscal year 1994–1995. The comparison was limited to youth with ADHD and youth with asthma. Case status was determined based on the presence of a relevant discharge diagnosis code during the year. Youth with no relevant diagnosis code but with three prescription fills for stimulant drugs or asthma medication were included. Youth with yearly claims exceeding $US10 000 were excluded (1994–1995 values). There were 1602 youth, 6% of the total sample, who met the criteria for ADHD and 1411 youth, 4% of the total sample, who met the criteria for asthma. Kelleher et al. compared the two groups for the number of outpatient visits (including outpatient hospitalisations, urgent care visits and ED visits that did not lead to an inpatient admission) during the year. Youth with ADHD had more visits than youth with asthma (mean ± SD = 29 ± 22 vs 20 ± 16); after adjusting for demographic differences, youth with ADHD had on average 33% more outpatient visits than those with asthma (p < 0.001).
Thus, existing studies provide consistent and convincing evidence that youth with ADHD have significantly increased ambulatory care use, with rates that are as high or higher than rates of use by children with asthma. In those studies that identified office visits for mental health services, the differences between youth with and without ADHD were even greater. There is some evidence, however, that rates of mental health service use for children with ADHD are less than those for youth with other mental health conditions. There is also evidence of variability in utilisation among youth with ADHD as a function of sociodemographic characteristics, the presence of comorbid conditions, use of stimulant medication, physician specialty, provider type and geographic region.
2.2 Emergency Department and Hospital Use
In contrast to the marked similarity across studies with respect to physician visits and mental health service use, there is less agreement regarding whether youth with ADHD experience higher rates of ED and hospital use compared with those without ADHD. The study of HMO enrolees by Guevara et al. found that, compared with age-sex-matched non-ADHD controls, the 2992 youth aged 3–17 years with a discharge diagnosis code for ADHD in 1997 were 2.1 times (95% CI = 1.8–2.4) more likely to be hospitalised in that year. The difference was limited to outpatient admissions (i.e., less than 24 hours); there was no difference between groups with respect to either the likelihood of an inpatient stay (1.5% vs 1.3%) or the number of inpatient days (0.04 ± 0.44 vs 0.05 ± 0.65; p = 0.23). Although the difference in average number of ED visits between youth with and without ADHD reached statistical significance, the rates were low and clinically insignificant (mean ± SD = 0.08 ± 0.33 vs 0.05 ± 0.26; p < 0.001). After adjustment for coexisting mental health disorders and specified medical conditions, there was also no difference between groups with respect to likelihood of an ED visit (OR = 1.1, 95% CI = 0.9–1.3).
Similarly, no difference in ED use was found in the study using 1996 MEPS data by Chan et al. Of the 165 subjects aged 5–20 years with informant-reported ADHD, 17% had an ED visit during the year of study compared with 18% for subjects with asthma and 10% for subjects with neither condition. There was no significant difference between subjects with ADHD and either those with asthma or those with neither condition in the frequency of ED visits (mean ± SEM = 0.23 ± 0.05; 0.28 ± 0.04 [p = 0.51]; and 0.16 ± 0.23 [p = 0.15], respectively) or in the frequency of hospital discharges (mean ± SEM = 0.04 ± 0.02 [p = 0.29]; 0.06 ± 0.02; and 0.03 ± 0.004 [p = 0.76], respectively).
The study of Medicaid-insured individuals in Pennsylvania, USA by Kelleher et al. found that the mean number of hospital inpatient days for youth with ADHD was lower than that for youth with asthma (mean = 0.1 vs 0.5). They did not compare the two groups specifically for rates of ED use. Increased rates of ED use for youth with ADHD were observed by Pastor and Reuben in their 1997–1999 NHIS study of children aged 6–11 years. The adjusted likelihood of an ED visit in the prior year for the 6.4% of children with an informant report that they had ever been diagnosed with ADHD was 22% compared with 16% for children never diagnosed with ADHD. The authors did not report on hospitalisations, but found no between-group difference with respect to the proportion who had surgery.
Leibson et al. is the only study to observe higher rates of both ED and hospital use for youth with ADHD compared with those without ADHD. The study used the longitudinal population-based resources of the Rochester Epidemiology Project. The study sample consisted of all children born to female residents of Rochester, Minnesota, USA between 1 January 1976 and 31 December 1982. The complete school records, as well as the provider-linked medical records, of birth cohort members were reviewed, and individuals were classified as having definite ADHD, probable ADHD, questionable ADHD, or no ADHD based on an algorithm that considered evidence of symptoms consistent with the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria, a confirmed clinical diagnosis of ADHD, and positive results on ADHD-related questionnaires. Data on medical care utilisation were obtained from administrative and billing data provided by the two group practices and three hospitals that have previously been shown to provide >95% of care delivered to local residents.
Leibson et al. followed the 4880 birth cohort members who were residing locally in 1987 (the first year utilisation data were available electronically) until emigration, death, or 31 December 1995 for discharge diagnoses, number of ED visits, hospital inpatient and outpatient admissions and inpatient days. ADHD case status was limited to the 350 youth (7.2%) who met the criteria for definite or probable ADHD between aged 5 years and either emigration, death, or 31 December 1995. Compared with youth without ADHD, those with ADHD were more likely to have been assigned diagnoses in multiple categories, including other psychosocial conditions, major injuries and asthma. Over the full 9 years of follow-up, the likelihood of at least one admission was significantly increased for individuals with ADHD compared with individuals without ADHD for hospital inpatient (26% vs 18%; p < 0.001), hospital outpatient (41% vs 33%; p = 0.006), and ED visits (81% vs 74%; p = 0.005). Compared with their non-ADHD counterparts, individuals with ADHD who were admitted experienced similar numbers of inpatient days (median: 3 vs 2; p = 0.30) and outpatient admissions (median: 2 vs 2; p = 0.10), but more frequent ED visits (median: 4 vs 3; p < 0.001).
It is somewhat surprising that only one study found that youth with ADHD were at increased risk of both ED use and inpatient hospitalisations in light of numerous studies showing that they are at increased risk of serious injury, accidents, poisoning, etc.[15,31, 32, 33, 34, 35] In the study by Chan et al., although they found no significant difference in rates of ED use among groups, 65% of all ED visits by youth with ADHD were related to injuries compared with 25% for youth with asthma and 50% for children with neither condition. Chan et al. acknowledged that their ability to demonstrate statistically significant differences was limited by small sample sizes. For each of the two studies that did observe increased ED use by persons with ADHD,[31,42] in addition to having ample person years of observation, ADHD case status was determined separately from utilisation data, and persons with no utilisation during the year were not excluded. If, as suggested by Leibson et al., youth with ADHD were more likely than youth without ADHD to have at least one medical encounter in a given year, studies that exclude persons with no activity will underestimate differences in the likelihood of an encounter between persons with and without ADHD. In addition, in studies that rely on utilisation data for identifying ADHD cases, activity by persons with ADHD who have a medical encounter during the year, but none specifically for management or treatment of ADHD, may be misclassified as non-ADHD activity. In such studies, the distribution of activity by persons with ADHD is likely to be biased toward encounters for ADHD management and treatment and against encounters that occurred for other reasons, prior to clinical diagnosis, and/or after pharmacological treatment was discontinued.
2.3 Pharmacological Treatment Rates
Perhaps the most controversial aspect of ADHD-associated medical care use is pharmacological treatment. The controversy is fuelled by the dramatic increases in ADHD pharmacological treatment that have been observed within the general population over time (see table I). For example, a study of methylphenidate use among youth aged <20 years in British Columbia, Canada revealed that rates have risen 5-fold from 0.2% in 1990 to 1.1% in 1996. The 1996 rates for British Columbia were similar to those from a 1995–96 Manitoba, Canada study revealing that 0.9% of youth aged 0–19 years had at least one prescription claim for stimulant medication. Both studies found marked variation as a function of physician specialty and geographic region.[44,45] Increasing rates of psychostimulant use among the general population in the past decade and marked variability across geographic regions have also been observed in Israel, the Netherlands, Australia, and in the US.
The most recent US NAMCS comparison reveals that the percentage of the population aged 5–18 years with an office visit for which there was a diagnosis of ADHD and a prescription for stimulant medication in 1997–1998 was 5.7% for boys (a 2.2-fold increase from the rate of 2.6% in 1991–1992) and 2.1% for girls (a 2.6-fold increase from the rate of 0.75% in 1991–1992). These rates are consistent with those found in a 1998 survey of youth enrolled in Maryland, US public schools. This survey revealed that 2.9% of students in kindergarten through to grade 12 were receiving medication for ADHD during school hours. The authors projected that, based on cited estimates that 20% of children only receive medication at home, the proportion of children and adolescents treated with medication for ADHD at school and/or home was 3.6% for both sexes combined. When limited to elementary school students, the proportion of Maryland public school children estimated to be receiving ADHD medication was 4.5%. This was lower than the 7% rate reported in a study that surveyed parents of students enrolled in grades one through five in Johnston County North Carolina, US public schools between 1997 and 1999. Even higher rates were found in a study based on North Carolina Medicaid prescription claims files. Rushton et al. reported that the prevalence of stimulant prescription fills among Medicaid recipients aged 6–14 years increased from 4.4% to 9.5% between 1992 and 1998. In 1998, stimulant prescription prevalence was highest for white school-aged males (18.3%) and lowest for black females (3.4%).
In contrast to the variability in the rate of treatment with stimulants in the general population, studies of the rate of treatment among youth with a clinical diagnosis of ADHD generally reveal more consistent findings. The study by Guevara et al. of pharmacy fills for persons aged 3–17 years enrolled in the Washington State, US HMO revealed that 78% of those with a discharge diagnosis code for ADHD in 1997 were on stimulant medications. Data from the CBS physician survey revealed that the percentage of youth aged 4–15 years with clinician-identified ADHD problems in 1996 who were receiving medication was also 78%. NAMCS data found over 75% of office visits with a diagnosis code for ADHD in 1996 involved management with stimulant medication. And in the study of Johnston County North Carolina, US elementary school children by Rowland et al., 71% of children whose parents reported that they had ever been given a diagnosis of ADHD were currently on medication for ADHD.
While the finding that approximately 25% of youth with a clinical diagnosis of ADHD are not receiving pharmacological agents might be interpreted as evidence of under-treatment, evidence of over-treatment is suggested by some studies showing that substantial numbers of youth are prescribed stimulant medication in the absence of a clinical diagnosis of ADHD. The study of Medicaid-insured youth in Pennsylvania, USA by Kelleher et al. revealed that, of all youth identified in claims files as having ADHD based on a discharge diagnosis code and/or three pharmacy fills for ADHD medication, 20% qualified on the basis of pharmacy fills alone. By contrast, in the MEPS study by Chan et al., only 4% of children defined as ADHD based on informant-reported clinical diagnosis and/or evidence of stimulant medication were identified through use of medication alone.
The relative consistency in rates of medical treatment among youth with a clinical diagnosis contrasts with the marked variability in both the rates of ADHD pharmacological treatment in the general population and in the proportion of medically-treated youth who are assigned a clinical diagnosis. This suggests that the source of variability lies not in the decision to treat an individual once they are diagnosed but rather in the decision as to whether or not to assign a diagnosis. Furthermore, this suggests that studies that identify ADHD cases based on clinical diagnosis or parental report of clinical diagnoses may be unsatisfactory for assessing the extent to which medical treatment for ADHD is inappropriately prescribed.
2.3.1 Clinically-Appropriate Pharmacological Treatment
Of the relatively few population-based studies in which ADHD case status was ascertained separately from clinical diagnoses, even fewer have reported the proportion of cases receiving pharmacological treatment.[4,5,8,43] The rates of treatment among ADHD cases in these studies again reveal variation across studies as well as within studies as a function of gender, age, ADHD subtype, race, and socioeconomic status.[4,8,43] The question of what rates of pharmacological treatment are clinically appropriate requires generally accepted guidelines as to what constitutes ‘appropriate’. In an excellent review, Miller et al. summarised the literature consisting of expert directives and recommendations. Furthermore, they contrasted this summary with current practice styles, as synthesised from eight surveys regarding physician management and treatment of ADHD. Based on their qualitative analysis, the authors concluded that, in 10–40% of treated cases, stimulant medication for ADHD may have been prescribed inappropriately.
A similar conclusion was reached by Angold et al. who analysed data from the Great Smoky Mountains, USA study, a study consisting of four annual waves of structured psychiatric interviews with parents of 9- to 16-year-olds. The authors reported that 72% of youth who met full Diagnostic and Statistical Manual of Mental Disorders, Version 3 Revised (DSM-III-R) criteria for ADHD between 1992 and 1996 received stimulant medications. This proportion is similar to that found in studies cited in section 2.3 that identified ADHD based on clinical diagnosis alone. Importantly, however, of the interviewed youth who received stimulant medications, a majority were never reported by their parents to have any impairing ADHD symptoms. Thus the authors concluded that over-treatment with stimulant medications was a concern. The conclusions of Angold et al. differ, however, from those from other studies that also used explicitly stated epidemiological criteria for identifying ADHD.
In an examination of data from four US communities as part of the Methods for the Epidemiology of Child and Adolescent Mental Disorders, Jensen et al. found that only 12.5% of children who met full DSM-III-R criteria in 1992 based on parent and child survey data were treated with stimulants in the prior 12 months. This finding led the authors to conclude that there was no evidence for substantial over-treatment with stimulant medication. In the study of children enrolled in special education programs by Bussing et al., the parents of 20% of all special education children stated their child was on medication for ADHD. However, an additional 24% of children met DSM-IV criteria for ADHD, as assessed in a second phase of their study using the National Institute of Mental Health Diagnostic Interview Schedule for Children. Indications of potential under-treatment were also found by Wolraich et al. in their study of students enrolled in kindergarten through to fifth grade during the 1993–1994 school year in a county in Tennessee, USA. Only 26% of those who met DSM-IV case criteria for ADHD based on teacher-completed behavioural rating scales that assessed ADHD symptoms were reported by the teacher as being treated with stimulant medication. Importantly, these authors defined ADHD case status applying both DSM-III-R and the more recent DSM-IV criteria and showed that the proportion of cases medically treated was less when DSM-III-R was used compared with when DSM-IV was used.
Thus, even among studies that ascertain ADHD case status using explicitly stated epidemiological criteria, there is evidence to support both over- and under-medical treatment of ADHD. Issues of case definition (i.e. DSM version used, the survey tool used and whether parent and/or teacher responses were considered) again contribute to some of the across-study differences. In addition, because a majority of studies were cross-sectional, the appropriateness of treatment in individuals who were medically treated but did not exhibit symptoms could not be assessed due to the possibility of treatment effect. Such assessment requires longitudinal follow-up at the level of the individual, such as that provided by the Great Smoky Mountains, USA study and with the Rochester, USA birth cohort study.[2,31] Using the Rochester cohort study, Barbaresi et al. observed that only 0.2% of youth with no evidence of ADHD in their school or medical records over the full period of follow-up were treated with stimulant medication. It is important to note, however, that the determination of ADHD case status in the Rochester birth cohort was retrospective. Of all individuals who met research criteria for ADHD, 9% met criteria on the basis of a clinical diagnosis in the medical record alone (i.e. absent positive questionnaires or meeting DSM-IV criteria), and 77% of individuals who met criteria on the basis of a clinical diagnosis alone were medically treated. This highlights perhaps the most important limitation to assessing the extent of over- or under-medical treatment of ADHD in studies to date, i.e. that there is no clearly objective measure of ADHD case status. All existing measures require some subjective determination, either on the part of the clinician, parent, or teacher. And, more importantly, that the appropriate determination of who is or is not a candidate for pharmacological treatment extends beyond whether or not an individual meets explicit diagnostic criteria to include clinical judgement and patient and family considerations.
3. Cost Analyses and Cost-Effectiveness Analyses
3.1 Incremental Medical Costs Associated with Attention-Deficit Hyperactivity Disorder
Although several studies have examined rates of ambulatory care and pharmacological treatment associated with ADHD, there are relatively few investigations of ADHD-related costs (see table II). Only three studies to date, all observational in design, have compared estimates of medical care costs between persons with ADHD and those without ADHD.[27,31,53] One additional cost comparison was performed by Kelleher et al. in their study of Medicaid-insured youth in Pennsylvania, USA identified with ADHD or asthma. Table II provides a summary of studies, methods and results. All studies clearly demonstrated that medical care costs are significantly higher for children with ADHD than for those without ADHD. However, there is less consensus as to where those medical costs associated with ADHD are occurring.
Kelleher et al. estimated Medicaid reimbursements for all services and for mental health services (including pharmaceutical and non-pharmaceutical reimbursements). After adjusting for between-group differences in disability status and demographic characteristics, mean total Medicaid reimbursements in 1994–1995 US dollars for youth with ADHD were similar to those for youth with asthma ($US1795 versus $US1666; p = 0.17). However, reimbursements for pharmaceuticals were 42% higher in youth with ADHD accounting for 28% of their total Medicaid reimbursements. The generalisability of findings to non-Medicaid populations may be problematic, given the high prevalence of stimulant prescription fills among the Medicaid population relative to that in studies of other populations as observed by Rushton et al. (see section 2.3). Study findings, however, were consistent with those reported by Chan et al. who compared persons with ADHD and those with asthma from a representative national sample.
The economic study by Chan et al. compared healthcare expenditures among youth with ADHD, youth with asthma and youth with neither condition. Healthcare expenditures, including out-of-pocket payments by families, for these cohorts of youth aged 5–20 years were assessed using the MEPS data described in section 2.1. The measure of expenditure in MEPS is the actual payment. According to Chan et al., unadjusted mean expenditures for healthcare in 1996 totalled $US1151 for youth with ADHD; this was 1.06 times the expenditures for youth with asthma ($US1090), and 1.62 times those for youth with neither condition ($US712) [1996 values]. After adjusting for sex, race, poverty status, insurance type, having a usual source of care, parent’s education and marital status, and region of the US, youth with ADHD incurred per capita incremental expenditures of $US479 (95% CI: $US193–765) compared with those with neither condition, while youth with asthma had per capita incremental expenditures of $US437 (95% CI: $US96–778) compared with those with neither condition. Chan et al. reported that expenditures for all prescriptions accounted for 27% of total healthcare expenditures for youth with ADHD, compared with 16% for those with asthma and 7% for those with neither condition (p values were not reported for the above data).
In an analysis limited to youth with ADHD, Chan et al. compared expenditures between those who had a prescription for stimulant medication during the year (n = 114) and those who had not (n = 51). Youth with ADHD who had received a prescription for stimulant medication during the year had total, outpatient visit, and prescription costs at least double those for youth with ADHD with no prescription for stimulant medication. ADHD youth with and without a prescription for stimulant medication did not differ in medical costs related to ED visits (p = 0.08).
Chan et al. also compared costs for persons with both ADHD and coexisting mental health diagnoses and costs for persons with ADHD alone. Although the authors cautioned that interpretation was limited by the small numbers, they found that the mean total expenditures for the 24 persons with both ADHD and at least one coexisting mental health diagnosis were $US2367 compared with mean total expenditures of $US997 for the 141 persons with ADHD and no coexisting mental health diagnoses.
In another comparison of medical care costs for persons (aged 3–17 years) with and without ADHD, Guevara et al. used the computerised patient information system of Group Health Cooperative (GHC) of Puget Sound, Washington State, USA to track healthcare service use. Costs per unit of service were assigned using the GHC Decision Information Support Center cost-accounting system that allocates overhead costs to individual clinical departments. Per unit costs, therefore, reflected provider costs for medical personnel, supplies, as well as overheads. Costs for services provided on a contractual basis to GCH services were based on GHC’s payment to these providers.
Guevara et al. found that mean total direct medical costs in 1997 values for youth with ADHD were 2.1 times higher than those for youth without ADHD ($US1465 vs $US690; p < 0.001). Compared with youth without ADHD, youth with ADHD had 1.7 times the primary care costs ($US427 vs $US245; p < 0.001), 11.0 times the outpatient mental health costs ($US222 vs $US20; p < 0.001), and 5.1 times the pharmacy costs ($US335 vs $US66; p < 0.001). Youth with ADHD had significantly higher mean ED costs ($US38 vs $US29; p < 0.001) and 8% lower hospital inpatient costs ($US115 vs $US125; p < 0.001), but the differences were small and clinically insignificant. Sixty-seven percent of total costs for youth with ADHD were attributable to primary care, outpatient mental health, and pharmacy costs. ED and inpatient hospital costs accounted for a small proportion of total costs. After controlling for age, sex, mental health conditions, and a limited number of chronic medical conditions, persons with ADHD incurred mean total incremental costs of $US1010 (95% CI: 798–1269).
Guevara et al. also compared costs for persons with both ADHD and coexisting mental health diagnoses and costs for persons with ADHD alone. Their findings were consistent with those from the nationally representative but smaller study by Chan et al. Guevara et al. found that 70% of persons with both ADHD and coexisting mental health diagnoses had total costs above the median for all youth with ADHD whereas only 30% of youth with a diagnosis of ADHD and no co-occurring mental health diagnoses had total costs above the median for all persons with ADHD. The higher costs for persons with co-occurring mental health conditions remained after adjusting for age, sex, and a limited number of chronic medical conditions.
Medical costs for youth (age range 5–19 years) with ADHD and without ADHD were also compared in the population-based birth cohort study by Leibson et al. Direct medical costs (excluding outpatient pharmacy costs) were tracked in administrative data for birth cohort members who were residing locally in 1987, the first year that billing data were available electronically, and were followed until death, emigration, or 31 December 1995. Economic data on actual charges billed were available in line-item detail, however, line-item charges were standardised to reflect an inflation-adjusted estimate of the costs of each service or procedure provided locally in 1995 constant dollars. Specifically, using a ‘bottom-up’ costing approach, resource utilisation was grouped into the Medicare Part A and B classification system; Part A-billed charges were adjusted by using hospital cost-to-charge ratios, and Part B physician services were adjusted by using 1995 Medicare reimbursement rates.
Economic analyses revealed that the median costs in 1995 dollars for all episodes of care during the 9 years of follow-up for individuals with definite or probable ADHD were more than double those for other individuals ($US4306 vs $US1944; p < 0.001). Medical care costs were higher for individuals with ADHD compared with those without ADHD in every year, even for the subset with no hospital or ED admissions (e.g. median 1987 costs, $US128 vs $US65; p < 0.001). The study findings were robust in separate analyses that considered definite cases alone and in analyses that defined ADHD cases using DSM-IV criteria. Comparisons of hospital and physician costs revealed that cost differences between individuals with and without ADHD were greatest for physician costs. The differences between individuals with and without ADHD were similar for males and females and across all age groups. The study by Leibson et al. did not include outpatient pharmacy costs. Thus, it is likely that including costs for pharmacological treatment for ADHD would reveal even greater differences in total costs between persons with and without ADHD.
3.2 Cost Effectiveness of Pharmacological Treatment
Beneficial effects of stimulant medications in reducing the core symptoms of ADHD have been demonstrated in several double-blind randomised controlled clinical trials and meta-analyses; with few exceptions, these studies have also demonstrated that the rate of adverse events is low and that the medications are generally well tolerated.[66, 67, 68, 69, 70, 71, 72, 73, 74] Primary outcomes in published efficacy trials tend to be based on changes in the symptom checklist and/or behavioural rating scale scores. Little evidence exists, however, establishing the effectiveness of stimulant medications on long-term meaningful outcomes (e.g. graduation rates) — likely contributing to the paucity of research on the cost effectiveness of pharmacological treatment. Only two complete economic evaluations (estimating incremental costs and incremental effects associated with treatment) have been published;[75,76] one partial economic evaluation has been conducted to estimate the expected total costs associated with pharmacological treatment and management.
Marchetti et al. used decision-analytical modelling techniques to estimate expected total direct costs associated with six commonly prescribed pharmacotherapies for treating school-age children with ADHD. The analysis was conducted from the payer perspective and considered medications, monitoring, and school-related costs. They surveyed clinical experts and public school personnel to identify clinical care components (e.g. office visits, laboratory tests and therapeutic interventions) and practice styles (e.g. frequency and type of visit, pathways of care, dosing schedules, etc.) to use in cost model development. Each component was assigned a monetary value based on published fee schedules, average wholesale prices, and survey responses. Treatment response rates were derived from a meta-analysis of the literature and were used to develop clinical scenarios that considered adjustment of medication, switching of medications and visits to mental health specialists. Estimates of the total costs associated with each of the six pharmacotherapies were based on these clinical scenarios and the costs of medical resources consumed through all pathways of care. Cost model results suggest that the average total annual per-patient expected cost ranged from $US1487–2232 (2001 values), depending on the specific pharmacotherapy under consideration. Cost estimates were sensitive to assumptions regarding drug acquisition costs and dosage administration regimens. When per-patient costs were multiplied by ADHD prevalence rates, the total expected cost for treating children with ADHD in the US ranged from $US2–11 billion.
Gilmore and Milne used a similar modelling approach to estimate the cost effectiveness of methylphenidate in the treatment of British children with hyperkinetic disorder. The analysis was conducted from the perspective of the National Health Service in the UK and estimated the incremental costs per QALY gained associated with a year of treatment compared with no stimulant drug treatment. They obtained information on drug dosage and number of outpatient clinic visits from a literature review and by contacting clinical experts via telephone interview or questionnaire. Per unit cost data were obtained from a variety of secondary sources. Effectiveness of methylphenidate treatment was based on published studies and The Index of Heath-Related Quality of Life (IHRQL) enabling them to estimate QALYs gained with treatment. Additional key model assumptions included: a drop-out rate of 6%; a 70% response rate; non-respondents and those terminating treatment would be treated on average for 6 weeks; and that there was an average of five outpatient visits in the first year of treatment for responders. Cost-effectiveness results revealed an estimated mean cost of £9177 ($US14 462) per QALY gained, with a range of £5965 ($US9400) to £14 233 ($US22 431) [1997 values; £1 = $US1.5759], conditional on the assumed gains in QOL obtained with treatment. Sensitivity analyses indicated that results were also sensitive to the assumed proportion of patients who drop out of treatment and assumptions regarding the pattern of behaviour changes in children over time.
Gilmore and Milne acknowledged that a key study limitation is the method they used to generate QALYs — in particular the use of the IHRQL to estimate the preference weights reflecting patient’s utility (QOL) with and without drug treatment. The IHRQL is not a sensitive tool for measuring the disabilities associated with hyperkinetic disorder, so extensive sensitivity analyses were undertaken to determine how robust model results were to changing estimates of gains in QOL expected with treatment. The authors concluded that the cost-effectiveness results were reasonably stable whatever assumptions were made, although better evidence is needed on the impact of treatment on patient and family QOL.
Another complete cost-effectiveness analysis of pharmacological treatment was conducted by the Canadian Coordinating Office for Health Technology Assessment as reported in Zupancic et al. and Shukla and Otten. The authors used changes in behavioural rating scales, as observed in published efficacy studies, as their measure of effectiveness. A decision analytical model was developed from the third-party payer perspective to estimate the incremental cost effectiveness of five different treatment alternatives available to a healthcare professional for the treatment of a child with ADHD: three pharmacological strategies (methylphenidate, dexamfetamine, and pemoline), one psychological/behavioural therapy, and one combination therapy of behavioural and methylphenidate treatment. Treatment alternatives were compared with each other as well as to the reference strategy of no treatment. The authors considered direct medical costs (medications, physician visits, laboratory costs and hospital costs) and effects of treatment (differences in the Abbreviated Conners Teachers Rating Scale) with a time horizon of 1 year. Information on current practice patterns and associated resource utilisation for an index case (9-year-old, 61 pound boy [27.7kg]) was based on expert opinion. The frequency of physician visits and laboratory testing was obtained from survey data and published guidelines. Unit prices were based on Intercontinental Medical Statistics data as well as provincial and hospital fee schedules. Full and partial drug compliance as well as adverse drug reactions were considered in the model.
Results of the economic analysis suggested that methylphenidate is the most cost-effective alternative for the management of ADHD. High-dose pemoline was the next best choice (based on estimated incremental cost effectiveness), but since the rare but fatal adverse effect of hepatic failure was not considered in the model, this conclusion should be viewed with caution. Additional study limitations discussed by the authors included the sensitivity of their results to patient drug compliance (data on compliance with these drugs and other agents are currently limited); the significant heterogeneity of efficacy studies included in meta-analysis (wide variation in study design, subject characteristics, and outcomes measures); and their key-model assumption that improvement in behavioural rating scales is a good surrogate for clinically significant improvements — a relationship that has not been established in the literature to date.[76,78]
The literature on medical care utilisation and costs for youth with ADHD confirms that ADHD is an important medical condition, with economic consequences beyond the recognised social, behavioural and academic outcomes. Although the number of cost studies to date is limited, the findings from these studies reveal that children and adolescents with ADHD have direct medical costs approximately double those for children and adolescents without ADHD. As a result of the high rate of healthcare service use per individuals, together with the high prevalence of ADHD in the population, the contribution of adolescents and children with ADHD to the medical care utilisation and costs by all youth is substantial.
Efforts to reduce the costs associated with ADHD will require additional information about where those costs are occurring. While data from most studies suggest that pharmacy costs, mental health service use, and follow-up office visits account for much of the increase, there is conflicting evidence on whether youth with ADHD utilise more ED and hospital services relative to their non-ADHD peers. It will be important to resolve this issue because, although ED and inpatient encounters are relatively infrequent compared with office visits, they are traumatic events and contribute disproportionately to total costs. Future economic evaluations should attempt to include sufficient person-years of observation to capture the costs of infrequent but high cost events and to include all costs associated with ADHD management and treatment strategies (e.g. outpatient pharmaceutical costs, out-of-pocket medical costs, school-related costs for delivery of medication, provision of mental health services and indirect costs to family members).
Beyond knowledge of where the costs are occurring, there is need for additional information regarding the reasons for increased utilisation. For example, if ED use is higher for youth with ADHD compared with those without ADHD, educational interventions to reduce such use need to be informed with an understanding of whether the ADHD-associated increases were associated with a greater likelihood of accidental injury versus a greater propensity by parents of ADHD youth to use the ED as a primary source of care. Existing investigations have currently been limited by a reliance on summary data from physician surveys or administrative data. Future investigations would benefit from additional clinical detail. Such detail would increase our appreciation of the reasons underlying increased utilisation but would also help identify those at greatest risk.
Further data are needed on the extent to which cost and utilisation vary as a function of patient characteristics, e.g. age, gender, race, socioeconomic status, insurance status, and comorbidity. The effect that comorbid psychiatric conditions have on ADHD-related costs was investigated by Guevara et al. and Chan et al. whose findings suggest that persons with diagnoses of both ADHD and coexisting mental health conditions had much higher medical costs relative to persons with ADHD and no mental health conditions, although the possible role of detection bias in these findings merits further investigation. Leibson et al. found that incremental costs for persons with ADHD were similar for males and females and across the age range. However, it is important to recognise that the estimate of total costs in this study excluded outpatient pharmacy costs.
Studies that did include outpatient pharmaceutical costs suggest that such costs account for approximately one-fourth of total costs observed for persons with ADHD,[27,53,54] and studies of the characteristics associated with the likelihood of pharmacological treatment among youth with ADHD reveal that teenagers are less likely than children to be treated and that girls have been less likely than boys to be treated.[4,8,41,43,80] Given that the likelihood of inattentive subtype is greater for girls than for boys, the latter finding is consistent with at least one observation that ADHD cases categorised as subtype inattentive are also less likely to be treated. Thus, there is a need for additional population-based studies that afford characterisation of ADHD cases by subtype and that obtain detailed data on payer status, diagnoses, services, and procedures. Such data would help to assure that: urgent care encounters for accidental injuries are categorised separately from office visits; that all mental health services are captured, irrespective of whether a referral was made; and that all diagnoses, not just those for ADHD or ADHD-related psychiatric conditions, are captured.
The use of samples that are nationally representative or with characteristics that are comparable to other populations would greatly increase the generalisability and comparability of future investigations. Comparability in study results would additionally be enhanced if researchers use explicitly stated epidemiological criteria for defining ADHD case status. As suggested in section 2.2, potential bias in estimates of ADHD-related utilisation and associated costs could be reduced if the determination of ADHD case status and that of comorbid conditions was based on data separate from utilisation and cost data. A fair amount of confusion in the literature stems from across study differences in case definition. In this regard, study designs that afford multiple case definitions[2,7, 8, 9,31,43] may lend some insight into across study differences and provide an opportunity to assess the robustness of study findings.
Research on the impact of ADHD treatment on medical care costs is also limited. Only one study to date, using patient level data, compared medical costs between youth with ADHD who were treated with stimulant medication and those who were not treated. Although the authors found that medically treated youth had total costs at least double those for non-medically treated youth, the finding should be interpreted with caution in the absence of any adjustment for potential confounding due to treatment bias. All other published pharmacoeconomic evaluations (partial and complete) have relied on expert opinion on current practice patterns and associated resource utilisation to estimate the impact of stimulant medications on total costs of care.
This review was focused on studies of ADHD-associated healthcare utilisation and direct medical costs for school age subjects. A more complete understanding of ADHD-associated costs will require consideration of broader, long-term outcomes. A number of studies suggest that ADHD youth are at increased risk for multiple adverse outcomes as adults, e.g. lower education level and socioeconomic status, tobacco use, substance abuse, psychological problems, legal problems and increased likelihood of incarceration.[20,21,23,25,82, 83, 84, 85, 86, 87] In the general population, these outcomes are known to have substantial economic consequences, both for the individual and society. With few exceptions,[20,86,87] investigations of the likelihood of these outcomes for persons with ADHD have largely been restricted to relatively small numbers of clinic-referred, primarily male subjects with ADHD-combined type (i.e. both inattentiveness and hyperactivity). In addition, while there is compelling evidence that short-term pharmacological treatment reduces the core symptoms of ADHD, and increasing evidence, again primarily from referral-based studies, that treatment may reduce the likelihood of later substance abuse,[88,89] there are very little data on the long-term effectiveness of drug (or other) treatments on other relevant outcomes. Thus, a full appreciation of the economic costs associated with ADHD and ADHD-treatment strategies will require long-term follow-up of representative, well-characterised samples of persons with and without ADHD. It is likely that such investigations will be limited to observational study designs.
Economic analyses that are observational in nature should pay particular attention to potential selection bias imposed by heterogeneous patient populations and consider emerging methods in health services research that attempt to address such bias, (e.g. instrumental variable analyses and propensity techniques).[90, 91, 92, 93] In addition, investigators should also choose model specifications shown to provide unbiased and precise cost estimates in the presence of often complicated cost data structures.[94,95]
This review of the literature reinforces that ADHD is an important medical condition with substantial economic costs. Accurate estimates of the magnitude of the increased costs are essential in order to adequately respond to the need for care. This is especially true in a period when the financial and human resources for caring for children with developmental learning and behavioural disorders are constrained.[4,57,58,96]
In order to assure efficient use of resources, there is a need for additional data on where the ADHD-associated increases in healthcare utilisation are occurring, the underlying reasons for the increases, and the characteristics of those at greatest risk. Increasingly, healthcare providers, third-party payers, and policy makers have come to rely on cost-effectiveness evidence when making decisions about reimbursement. Additional information on the costs and benefits associated with ADHD diagnosis, management, and treatment is therefore also essential for guiding clinical practice and health policy.
We thank Drs Slavica Katusic and William Barbaresi for their helpful reviews and comments. Dr Leibson is funded in part by McNeil Consumer and Specialty Pharmaceuticals. The authors have provided no information on conflicts of interest directly relevant to the content of this review.
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