Global interest in attention deficit hyperactivity disorder (ADHD) is on the rise (Hinshaw et al., 2011). ADHD has only been recently recognized on an international scale as a serious medical condition with long-term consequences (Garcia-Jimenez et al., 2005; Wilcox et al., 2007; Curatolo et al., 2010; Davis et al., 2011; Lecendreux et al., 2011). Historical evidence, however, attests that ADHD symptoms have been described in individuals in many different countries. For example, Jean-Baptiste Poquelin, known as Molière – the French theater author – may have been one of the first people to describe a character with symptoms of ADHD in “L’étourdi ou les contretemps” (translated into English as the scatterbrain or the bungler) in as early as 1653 (Bange and Mouren, 2009). In 1798 Scottish physician Sir Alexander Crichton wrote of a disorder characterized by inattention and restlessness that affects schooling (Palmer and Finger, 2001). Heinrich Hoffman (1844–1845) was a German psychiatrist who wrote children’s stories including the agitated child character known as “fidgety Phil” and the inattentive “Johnny, who looks in the air” (Thome and Jacobs, 2004). The first report of stimulant administration to children for ADHD-like symptoms was published by Charles Bradley in the US in 1937. He reported that the academic performance of students with ADHD-like symptoms immediately improved after stimulant administration (Bradley, 1937; Findling, 2008).

The first diagnostic description of what is now called ADHD occurred in The International Statistical Classification of Diseases Ninth Edition (ICD-9) and The Diagnostic and Statistical Manual of Mental Disorders, Second Edition (DSM-II) in 1965 and 1968, respectively. ADHD was called hyperkinetic syndrome of childhood (Stubbe, 2000) or hyperkinetic reaction (DSM-II). This term remains in the current ICD-10 as hyperkinetic disorder. In the next edition, DSM-III, came the first definition of attention deficit disorder (ADD) with or without hyperactivity 1980 (Lange et al., 2010). In the DSM-III-R the term was changed to ADHD, which has persisted to the present. The DSM-IV added subtypes of predominantly hyperactive, predominantly inattentive, and combined (Lange et al., 2010). The addition of the inattentive subtype increased the number of people meeting diagnostic criteria using the DSM-III-R by approximately 24% (Lahey et al., 1994). While the definition of ADHD was not changed for the DSM-IV-TR, it is anticipated that sub-typing may expand for the upcoming 2012 DSM-V to add a fourth subtype known as inattentive-restrictive, which is characterized almost exclusively by inattentive symptoms, with minimal hyperactive symptoms (Nigg et al., 2010; APA, 2011).

DSM-IV and ICD-10 have similar criteria for inattentive, hyperactive, and impulsive symptom identification. However, the ICD-10 is stricter than the DSM-IV, with a demand for each symptom to be present across school, home, and other settings in order to be counted (Lange et al., 2010). Unlike the DSM-IV-TR which allows sub-typing based on hyperactive/impulsive or inattentive predominance as well as the combination of both, ICD-10 requires both inattentive and hyperactive/impulsive symptoms for diagnosis (EMEA, 2010). ICD-10 also excludes children with co-occurring conduct disorders (Stubbe, 2000) but has a parallel diagnosis of hyperkinetic conduct disorder, which would mainly reflect comorbid ADHD combined type with conduct disorder or oppositional-defiant disorder. In reflection of the more stringent ICD-10 criteria, when the MTA combined type ADHD sample was re-diagnosed by ICD criteria, only 25% met the criteria for hyperkinetic disorder or hyperkinetic conduct disorder (Santosh et al., 2005). In addition, Polanczyk et al. (2007) showed in their meta-regression analysis that ADHD prevalence differs by criteria used (DSM-III, DSM-IV, or ICD-10), and by informant (clinician versus teacher versus parents).

Almost four centuries ago, an ADHD-like pattern of behavior was described in adults by the French author Molière (Bange and Mouren, 2009). Considering more scientific and medical works, it appears that the persistence of ADHD in adulthood was recognized as soon as the beginning of the twentieth century by English (Still, 1902), French (Philippe and Paul-Boncour, 1905), and German (Kraepelin, 1909–1915) authors. Despite these observations, prior to 1972 it was still commonly viewed as a childhood disorder (Arnold et al., 1972). The first clinical trial in adults was conducted by Wender and colleagues in 1976 (Wood et al., 1976). ADHD therefore clearly affects both children and adults, occurring throughout the life-span with a prevalence of 5–10% in childhood, 4% in adults, and about 50–65% persistence (depending on whether ADHD was defined as fully symptomatic or with residual symptoms; Faraone et al., 2006; Kessler et al., 2006; Polanczyk et al., 2007; Kooij et al., 2010; Young and Amarasinghe, 2010). A recent study demonstrated that even older adults (mean age 66 years) suffer from ADHD symptoms and impairments based on measurements of professional, economic, social, and emotional well-being (Brod et al., 2011). The potential persistence of ADHD into adulthood makes long-term consequences important for study, and the global differences that exist in study design are of interest in the interpretation of ADHD long-term outcomes (LTOs). Many studies of ADHD have been conducted in the US, Canada, and Europe. The overall global recognition of the impact of ADHD is increasing, however, with more geographical regions beginning to appreciate the consequences of ADHD on society.

The attention lapses, hyperactivity-impulsiveness, or combination of symptoms caused by ADHD (APA, 2000; WHO, 2010) can lead to wide-ranging negative long-term life consequences (Rasmussen and Gillberg, 2000; Mill et al., 2006). Prior focus for the treatment of ADHD has been on symptomatic control. Patient management has shifted in recent years to include more focus on functional impairment. A negative impact on psycho-social, achievement, and self evaluation domains has been reported by parents of children with ADHD (Danckaerts et al., 2010). Functional impairment in multiple domains has been measured with tools such as functional magnetic resonance imaging, electrophysiology, and tests of cognitive performance, although these are not currently used as diagnostic tools (EMEA, 2010).

The differences in recognition of ADHD could be one factor that influenced reported prevalence in different world regions. For example, Polanczyk et al. (2007) showed in their meta-regression analysis that prevalence did differ when comparing different world regions. This study showed that the North American rate (6.2%) was only slightly higher than the European rate (4.6%). The highest rates of ADHD diagnosis were observed in Africa (8.5%) and South America (11.8%), but with a wide range of prevalence rates between studies. According to Polanczyk et al. (2007), the overall worldwide prevalence of ADHD is 5.3%. The recent epidemiological studies across the world support the notion that ADHD is a ubiquitous disorder and not merely a Northern American social construct (Moffitt and Melchoir, 2007).

The current systematic review was performed with the goal of: (1) identifying peer-reviewed studies reporting LTOs (two or more years) for people with ADHD published from 1980 through 2010, and (2) to address the following research question via comprehensive analysis of all studies identified; are there differences in outcomes studied by region, either in total or over time?

To systematically identify published studies that examined LTOs (i.e., life consequences) of participants with untreated or treated ADHD, an extensive search of 12 literature databases was performed using a strategy based on the following inclusion and exclusion criteria. Only studies identified in these databases using electronic search engines and this search strategy were included. Studies including a group of participants with ADHD as determined by each study’s authors using any diagnosis criteria were included. To ensure a basic level of study quality, only peer-reviewed studies and only studies utilizing a comparator group (e.g., non-ADHD controls) or comparison measure (e.g., pre-treatment baseline) were included. Studies of participants that had received any or no ADHD treatment were included. Longitudinal studies with prospective follow-up or retrospective measures of 2 years or more, cross-sectional studies comparing participants of two ages differing by 2 years or more, or single cross-sectional studies of participants ≥10-years-old were included. Primary research articles published in English from January 1980–December 2010 inclusive, with available full-text were included. Studies examining symptoms only and not outcomes were excluded. Studies in which ADHD was not a primary condition of the study participants, but was secondary to another condition (e.g., intellectual disabilities or bipolar disorder), were excluded. Animal studies, case studies, and studies including only children younger than 2 years old were excluded. Meta-analyses and literature review studies were also excluded.

The search strategy for study identification was as follows. Inclusionary terms were: (1) names of the condition; ADD (captured all versions of ADHD), hyperkinesis or hyperkinetic, TDAH (trouble déficit de l’attention/hyperactivité in French or trastorno por déficit de atención con hiperactividad in Spanish, DAH (déficit de l’attention/hyperactivité in French or déficit de atención con hiperactividad in Spanish), DAA (déficit de l’Attention/activité in French or déficit de atención y actividad in Spanish), and (2) LTOs; long-term, longitudinal, education, degree, socioeconomic, salary, divorce, relationship, hobbies, criminality, arrest, incarceration, automobile, car, driving, citation, weight, obesity, suicide, drug abuse, addiction, substance abuse, alcoholism, and (3) comparator condition or group; control, proband, placebo, untreated, no treatment, pre-treatment, comparator, follow-up, normal, compare. Exclusionary terms were: (1) developmental, causal, or symptom terms; neuroanatomy, neuropathology, molecular, gene, development, etiology, preclinical, dose-finding, reaction time, and (2) unsuitable publication types; reprint, review, conference presentation. A more detailed explanation of the search methodology is available upon request. All references retrieved are included in the appendix.

To identify as many studies as possible, the search utilized 12 databases: Academic Search Premier, CINAHL, Cochrane CRCT (including EMBASE), Criminal Justice Abstracts, ERIC, MEDLINE, Military and Government collection, NHS Economic Evaluation database, PsycARTICLES, PsycINFO, SocINDEX, and Teacher Reference Center. Two search engines were used to search MEDLINE. Duplicates were eliminated electronically and manually. Additional unsuitable publication types were eliminated manually, including editorials, comments, reviews, non-peer-reviewed articles, and letters.

Based primarily on title and abstract, remaining studies were manually reviewed and included based on the agreement of two researchers. Each study’s data was extracted into a database; data collected included: (1) study location (country of origin), (2) study sample size, (3) study length, (4) participant’s age range, (5) study support, (6) diagnostic criteria, (7) study type (longitudinal, cross-sectional, prospective, retrospective), (8) outcome measures, (9) outcome results, (10) comparator type, (11) treatment type, and (12) treatment duration. Similar outcome measures were grouped together.

For the purpose of examining studies of ADHD originating in different geographical regions of interest, studies were grouped by location according to the UN Geoscheme (UN, 2011). Major regions included Northern America (United States and Canada excluding Mexico), Europe, Eastern Asia, Western Asia, Oceania (New Zealand and Australia), and Latin America (including Mexico) and the Caribbean. International collaborations were also of interest.

For the purpose of examining studies of ADHD involving participants of different ages, the age range of participants was noted whenever possible and mid-range age was calculated. If the age range was not reported, the mean age was used. The mid-range/mean age was used to group each study into one of three age groups: children were 6- to 12-years-old, adolescents were between 13- and 17-years-old, and adults were above 17 years old. For mid-range ages 18–22, the minimum and maximum ages were also taken into account. If the minimum age was 16 years or younger and the maximum age was below 30 years, then the study was grouped with adolescent studies, rather than adult studies. For further analysis of studies of adults specifically, the age range/mean age was used directly to group studies into three adult groups: transitional adults (18- to 24-years-old), young adults (25- to 44-years-old), and mature adults (45- to 64-years-old).

Dr. Hodgkins is an employe of Shire Development Inc., owns Shire stock and has stock options. Dr. Arnold has received research funding or consulting fees from Astrazeneca, Biomarin, Curemark, Lilly, Novartis, Noven, Seaside Therapeutics, and Shire (nothing for contributing to this article). Dr. Shaw was an employee of Shire Pharmaceuticals, Ltd., when this analysis was conducted and when this manuscript was drafted. Dr. Caci has received consulting fees from Shire (nothing for contributing to this article). Dr. Kahle is owner of BPS International. BPS International received funding from Shire Development Inc., to perform this analysis and participate in writing this manuscript. Dr. Woods is a consultant for BPS International and has been a consultant for Shire Development, Inc. Dr. Young has received research funding or consulting fees from Janssen-Cilag, Eli-Lilly, Novatis, Flynn-Pharma, and Shire (nothing for contributing to this article). She was a member of the UK NICE Guideline Development Group for ADHD. Funded by Shire Development Inc., Wayne, PA, USA. An earlier version of this analysis was presented as a poster (Shaw et al., 2011).