Journal of Attention Disorders

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Is ADHD a Risk Factor Independent of Conduct Disorder for Illicit Substance Use? A Meta-Analysis and Metaregression Investigation Maria Antonia Serra-Pinheiro, Evandro S. F. Coutinho, Isabella S. Souza, Camilla Pinna, Dídia Fortes, Catia Araújo, Claudia M. Szobot, Luis A. Rohde and Paulo Mattos Journal of Attention Disorders published online 17 February 2012 DOI: 10.1177/1087054711435362

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Articles Journal of Attention Disorders XX(X) 1–11 Is ADHD a Risk Factor Independent of © 2012 SAGE Publications Reprints and permission: sagepub.com/journalsPermissions.nav Conduct Disorder for Illicit Substance DOI: 10.1177/1087054711435362 Use?: A Meta-Analysis and Metaregression http://jad.sagepub.com Investigation

Maria Antonia Serra-Pinheiro1, Evandro S. F. Coutinho2, Isabella S. Souza1, Camilla Pinna1, Dídia Fortes1, Catia Araújo1, Claudia M. Szobot3, Luis A. Rohde3, and Paulo Mattos1,4

Abstract Objective:To investigate meta-analytically if the association between ADHD and illicit substance use (ISU) is maintained when controlling for conduct disorder/oppositional-defiant disorder (CD/ODD). Method: A systematic literature review was conducted through Medline from 1980 to 2008. Data extracted and selections made by one author were reviewed by another. Results: Fifteen articles presented odds ratios (ORs) for the development of ISU in individuals with ADHD controlling for CD/ODD. In total, the study covered results for more than 1,000 individuals. The combined OR for studies that included in their analysis exclusively ISU was 1.35 (0.90-2.03), p = .15, heterogeneity = 55%. Lack of control for socioeconomic status was related with a weaker association between ADHD and ISU. Conclusion: The existing data do not indicate that ADHD increases the risk of ISU beyond the effects of CD/ODD. However, the combination of all existing data is limited in power to detect a small increase in chance. (J. of Att. Dis. 2012; XX(X) 1-XX)

Keywords ADHD, drug, substance, conduct disorder, comorbidity

Introduction a high level of impulsivity and has been associated with executive functioning impairments (Bramham et al., 2009); ADHD has been repeatedly associated with illegal substance these cognitive impairments could lead to inadequate evalu- use. The evidence for this association comes from cross- ation of choices and poor decision making, in turn leading sectional (Molina, Smith, & Pelham, 1999) and prospective to ISU and SUDs (Dom, Hulstijn, & Sabbe, 2006). Adolescents studies (Mannuzza et al., 1991) demonstrating higher rates with ADHD often have deviant peer relationships (Marshal, of illicit substance use (ISU) and/or substance use disorders Molina, & Pelham, 2003), which is also associated with (SUDs) in individuals with ADHD. The high prevalence of ISU (Wills, Sandy, Yeager, Cleary, & Shinar, 2001). Finally, ADHD in patients with SUDs also suggests this association polymorphisms at dopaminergic genes have been associ- (Matsumoto, Kamijo, Yamaguchi, Iseki, & Hirayasu, 2005; ated with increased predisposition not only for ADHD Szobot et al., 2007). A recent meta-analytical study (Charach, (LaHoste et al., 1996) but also for SUDs (Pato, Macciardi, Yeung, Climans, & Lillie, 2011) also indicated that ADHD seems to be related to nonalcohol SUD, even though they 1Federal University of Rio de Janeiro, Brazil found large heterogeneity among studies. 2 There are many possible explanations for an association National School of Public Health–Oswaldo Cruz Foundation, Rio de Janeiro, Brazil between ADHD and ISU. ADHD may contribute to the 3Federal University of Rio Grande do Sul, Porto Alegre, Brazil emergence of disruptive behavior disorders (DBDs; Burns 4D’Or Institute for Research and Education (IDOR) & Walsh, 2002; Coté, Tremblay, Nain, Zoccolillo, & Vitaro, 2002) increasing the risk for ISU and SUD. ADHD may Corresponding Author: compromise academic achievement; some evidence has Maria Antonia Serra-Pinheiro, Psychiatric Institute of the Federal University of Rio de Janeiro, Rua Visconde de Pirajá, 330/906, Ipanema, demonstrated that low academic achievement is a risk fac- Rio de Janeiro, RJ, 22081-010, Brazil. tor for ISU (Hallfors et al., 2002). ADHD is associated with Email: [email protected]

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Pato, Verga, & Kennedy, 1993). Thus, there is a clear rationale hyperactivity, attention deficit (/) hyperactivity disorder, for the association of ADHD, ISU, and SUDs through a ADHD; drug, substance; and conduct, conduct disorder, CD, combination of different pathways, including a common oppositional-defiant, oppositional-defiant disorder, ODD, genetic vulnerability, a direct clinical expression (impulsiv- disruptive, antisocial. In addition to the electronic search, ity), impairment (low academic achievement), or the devel- references of selected articles were also examined, as well as opment of comorbidity (raising the possibility of emergence other articles pertinent to the issue that the authors were of conduct disorder [CD]). aware of and that were not retrieved in the electronic search. The high comorbidity between CD and other antisocial All the abstracts retrieved in the electronic research were behaviors with ADHD has been considered a very appeal- examined independently by two of the authors, and a rec- ing explanation for the association between ADHD and ommendation made as to whether the article should go SUDs. As CD is related to SUDs and ADHD, some investi- through a full-text review. When one of the abstracts was gators argue that the higher rates of SUDs found in indi- selected by one author and not by the other, a third reviewer viduals with ADHD are entirely due to the effects of CD defined whether that abstract was to be considered in full (Fergusson, Horwood, & Ridder, 2007) and ADHD would text. After the full-text review, articles that met the criteria play no role in increasing the risk for SUDs. However, there for inclusion/exclusion were subsequently examined by two are some findings suggesting that ADHD itself increases different authors. Data extracted from these articles were the risk for SUDs (Mannuzza, Klein, Bessler, Malloy, & first retrieved by one author and then subsequently verified Lapadula, 1993; Szobot et al., 2007). ADHD could have an by a second author. Discrepancies in interpretation of the effect on individuals without CD (Mannuzza et al., 1993) or data were discussed. it could make the risk of SUDs in individuals with CD and Articles were included if they were original reports in ADHD higher than in individuals only with CD (Flory & English and included the evaluation of risk of use of illegal Lynam, 2003). Based on the findings reported in the refer- substances (substances other than tobacco and alcohol) by ences cited above, this is a relevant clinical question still controls versus individuals with ADHD. They also needed unresolved by the available literature. to present some degree of control for conduct symptoms. There are many methodological differences in the avail- Studies presenting odds ratio (OR) with confidence inter- able studies evaluating ADHD as a risk factor for SUDs vals (CI; or data from which this information could be when controlling for CD, such as gender differences in the retrieved) for ADHD versus controls were included in the composition of samples, lack of adjustment for DBD in meta-analysis. controls, different age range for the assessment of SUDs, Articles were excluded if they were reviews or earlier and limitations inherent of the study designs. Some of these reports of a sample described in an article already included study characteristics could explain the different findings. in the search. Previous meta-analyses on the subject were Given the conflicting results and especially the limitations not found. Cross-sectional studies involving clinical sam- in power of the many studies investigating ADHD, ISU, and ples of ADHD patients were excluded due to possible refer- SUDs, a meta-analysis is a relevant approach to further ral bias. Studies conducted in special populations (such as address these topics. To the best of our knowledge, such an incarcerated or delinquent individuals) were also excluded analysis, in other words, a meta-analysis investigating because increased risk factors related to ADHD could lead to ADHD as a risk factor for isu/sud, while controlling for dis- an overrepresentation of ADHD in these samples. Studies ruptive disorders, is currently lacking in the literature. evaluating exclusively stimulant abuse were not included We sought to disentangle the relationship between CD, because the availability of the substance is evidently greater ADHD, and ISU (or SUDs when possible), and more spe- for individuals with ADHD, and reasons to engage in abuse cifically, to verify if ADHD itself implies an augmented risk could also be different from the factors leading to the use of of using illicit substances. Thus, the aim of this article is to the illicit substances herein investigated. Studies in which systematically review and analyze studies investigating this the measure of licit substance use and ISU was combined issue, discuss possible reasons for discrepancies, and esti- were excluded, due to the impossibility of inferring infor- mate the magnitude of the association, if any, between mation specifically related to ISU. ADHD and ISU/SUD, beyond the effect of CD. If studies presented multiple outcome measures for the same sample, the following choices were made:

Method a. when available, the measure for SUDs was A systematic literature review and a meta-analysis were adopted instead of that for substance use; carried out including observational studies with data on the b. when a measure was not given for SUDs (i.e., relationship between ADHD and ISU/SUDs. A literature abuse and/or dependence), but was available for search was conducted through PubMed for the period from abuse and dependence independently, the measure 1980 to 2008. Terms used in the search were inattention, used was that for abuse instead of dependence;

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c. when a summary measure for all ISU under control for socioeconomic level, ADHD diagnostic rule review was not presented, but measures for each (AND, best estimate procedure or OR)1, teacher involved or illicit substance were given separately, use of not in the diagnosis of ADHD, teacher involved or not in the cannabis was adopted as a proxy as it is the most diagnosis of CD, diagnostic awareness of researchers (if the widely used illicit substance (Johnston, O’Malley, interviewer who rated for SUDs was blind for ADHD or Bachman, & Schulenberg, 2005); and not), instrument used for ADHD diagnosis (interview or d. in the case of prospective studies, when measures questionnaires), and attrition level of the samples. were given for earlier and later ISU or SUDs, the Metaregression models were fitted using the log of the latter measure was used. OR as dependent variable and study characteristics as independent ones. Initially, each variable was entered sepa- The rationale for using the measure of SUDs instead of rately in the metaregression model. In the second step, use (when both were available) was the fact that it is a more those variables with p values equal to or smaller than .20 relevant measure from a clinical perspective. Studies evalu- were entered in a multivariate metaregression model, using ating use, however, were also included because ISU can be a forward strategy. Variables with p values equal to or less a precursor of SUDs and both have similar risk factors. than .10 were retained in the final model. Also, variables Nevertheless, the implications of using a potentially hetero- regarded as confounding factors were included in the final geneous group of individuals was taken into account during model. The criterion for confounding was a change of at the statistical analysis, by introducing alternatively ISU or least 10% in the magnitude of the OR of the interest vari- SUD as an independent variable in the meta-regression. able when the confounding factor was introduced in the To investigate the increment in the chance of developing multivariate model. Sensitivity analysis was performed to ISU or SUDs in individuals with ADHD, a meta-analysis deal with outlier studies. was performed to obtain a pooled estimate of the OR from different studies, controlling for CD. Fixed and random models were initially fitted. The presence of heterogeneity Results between the results of the various studies was investigated Number of Studies and Participants by the chi-square test for heterogeneity and the I2 index (Higgins, Thompson, Deeks, & Altman, 2003). This index Of more than 3,000 articles (3,094) found through the elec- describes the percentage of total variation across studies tronic search implemented (Figure 1), 180 were chosen for which is due to heterogeneity rather than chance. The ran- full-text review. Thirty-nine were finally selected: August dom effects model was used for I2 larger than 25%. Power et al., 2006; Barkley, Fischer, Smallish, and Fletcher, 2004; calculation was carried out for the pooled ORs. Barkley, Anastopoulos, Guevremont, and Fletcher, 1991; A metaregression model was fitted to verify if any of the Barkley, Fischer, Edelbrock, and Smallish, 1990; Biederman studies’ characteristics had an influence on the inconsistent et al., 2006; Biederman, Wilens, Mick, Spencer, and Faraone, results (heterogeneity) of the different studies. Characteristics 1999; Burke, Loeber, and Lahey, 2001; Chilcoat and Breslau, analyzed in the model were study design (prospective or 1999; Chong, Chan, and Cheng, 1999; Costello, Mustillo, not), nature of the sample (clinical or nonclinical), the geo- Alaatin, Keeler, and Angold, 2003; Danckaerts, Heptinstall, graphic origin of the sample (United States, outside the Chadwick, and Taylor, 2000; Disney, Elkins, McGue, and United States), gender of the sample (boys, girls, or mixed), Iacono, 1999; Elkins, McGue, and Iacono, 2007; Ernst et al., type of substance use (SUD also including problematic use 2006; Fischer, Barkley, Smallish, and Fletcher, 2002; as opposed to only use), the nature of disruptive symptoms Gadow, Sprafkin, Schneider, and Fletcher, 2007; Gau et al., controlled for (oppositional-defiant disorder [ODD], CD 2007; Gittelman, Mannuzza, Shenker, and Bonagura, 1985; [or antisocial personality disorder], or only CD or antiso- Greene, Biederman, Faraone, Sienna, and Garcia-Jetton, cial personality disorder), use of pharmacotherapy (at 1997; Hofstra, van der Ende, and Verhulst, 2002; Hinshaw, least 70% of the sample medicated, as opposed to no infor- Owens, Sami, and Fargeon, 2006; Hurtig et al., 2007; mation on pharmacotherapy or less than 70% of the sam- Lambert, Mcleod, and Schenk, 2006; Lee and Hinshaw, ple medicated), the age of control for disruptive symptoms 2006; Mannuzza et al., 1991; Mannuzza, Klein, Bessler, (before or simultaneous with the substance use), the age of Malloy, and LaPadula, 1998; Marshal et al., 2003; Marshal investigation of substance use (sample mean age of at least and Molina, 2006; McGee, Prior, Williams, Smart, and 18 or with minimum age range of 16, as opposed to a Sanson, 2002; Milberger, Biederman, Faraone, Wilens, and younger sample), diagnostic criteria for ADHD (Diagnostic Chu, 1997; Molina and Pelham, 2003; Molina et al., 2007; and Statistical Manual of Mental Disorders [4th ed.; Monuteaux, Faraone, Gross, and Biederman, 2007; Smalley DSM-IV; American Psychiatric Association, 1994] or not), et al., 2007; Sourander et al., 2007; Szobot et al., 2007; nature of the controls (also controlled for CD or not), addi- Taylor, Chadwick, Heptinstall, and Danckaerts, 1996; tional control for other psychiatric diagnoses, additional Roberts, Roberts, and Xing, 2007; Upadhaya et al., 2005.

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Figure 1. Fluxogram of the articles included in the meta-analysis Note: MASP = Maria Antonia Serra-Pinheiro; CA = Catia Araujo; IS = Isabella Souza; DF = Didia Fortes

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Table 1. Studies’ Results and Main Characteristics

Geographical Substance use × origin of the Gender Substance use Article OR [95% CI] Study design sample Pharmacotherapy distribution disorder August et al. (2006) 0.56 [0.19, 1.65] Prospective United States NR Mixed SUD Barkley et al. (2004) 0.69b [0.32, 1.49] Prospective United States 14.7%-16.3% Mixed Use Biederman, Wilens, Mick, 3.1 [0.8, 12.5] Prospective United States 0% Boys SUD Spencer, and Faraone (1999) Disney, Elkins, McGue, 1.83a [0.57, 5.84] Cross-sectional United States 20% Girlsa SUD and Iacono (1999; females) Disney et al. (1999; 0.8a [0.31, 2.04] Cross-sectional United States 20% Boysa SUD males) Elkins, McGue, and 0.58 [0.28, 1.20] Prospective United States NR Mixed SUD Iacono (2007) Ernst et al. (2006) 0.48 [0.14, 1.63] Prospective United States 30% (stimulants) Mixed Use Fergusson, Horwood, and 1.84b [0.95, 3.55] Prospective New Zealand NR Mixed SUD Ridder (2007) Mannuzza, Klein, Bessler, 4.62b [1.11, 22.10] Prospective United States Great majority Boys SUD Malloy, and Lapadula treatedb (1993) Molina and Pelham 1.4 [0.69, 2.82] Mixedc United States NR Mixed Use (2003) Molina, Smith, and Pelham 1.97 [0, 8.92] Cross-sectional United States NR Mixed Use (1999) Roberts, Roberts, and 1.5 [0.2, 11.5] Cross-sectional United States NR Mixed SUD Xing (2007) Szobot et al. (2007) 9.12 [2.84, 29.31] Cross-sectional Brazil None Boys SUD Upadhaya et al. (2005) 2.56 [1.17, 5.61] Cross-sectional United States 100% Mixed Usea Young, Heptinstall, 0.71b [0.03, 19.05] Prospective England NR Girls SUD Sonuga-Barke, Chadwick, and Taylor (2005) Note: OR = odds ratio; CI = confidence interval; NR = not reported; SUD = substance use disorder. aBecause the authors gave an OR for the sample of boys and another one for the sample of girls in the same article, we presented this data separately. However, the percentage treated is based on the entire sample, combining the sample of boys and girls examined in the article. bBased on additional data from the authors and from Mannuzza et al., 2008. cCases were prospectively followed, but controls were gathered cross-sectionally.

The 141 remaining articles were excluded due to the fol- measure, 15 articles—August et al., 2006; Barkley et al., lowing reasons: (a) lack of control for DBD, (b) lack of 2004; Biederman et al., 1999; Disney et al., 1999; Elkins assessment of ISU risk, (c) lack of stratification of cases et al., 2007; Ernst et al., 2006; Fergusson et al., 2007; with ADHD and controls, (d) were not original studies, (e) Mannuzza et al., 1993; Molina and Pelham, 2003; Molina cross-sectional studies of clinical samples, and (f) were et al., 1999; Roberts et al., 2007; Sourander et al., 2007; conducted exclusively with delinquent individuals. Twenty- Szobot et al., 2007; Upadhaya et al., 2005; and Young, three additional studies were included for full review from Heptinstall, Sonuga-Barke, Chadwick, and Taylor, 2005— expert sources or reference lists. After exclusion of dupli- were included in the meta-analysis. In all such cases, they cated samples and of studies which (a) did not report data presented results in OR with CI for different categories on OR with CI (or whose author did not inform this infor- (ADHD and controls) or presented data in the article or mation after request), (b) did not report their results due to through information from authors that made possible the nonsignificance, and (c) combined licit and ISU in a single calculation of this information. In total, more than 1,000

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individuals were covered. The main results and characteris- the results of all 15 studies are combined, is limited. Thus, one tics of each study are presented in Table 1. cannot infer from the existing literature, taken individually or when combined, whether or not there is an association between ADHD and ISU and/or SUDs, when controlling Meta-Analysis for DBDs. The pooled chance of ISU/SUD was 1.35 higher (95% CI = It is perhaps surprising not to find a significant associa- [0.90, 2.03], p = .15) among those with ADHD compared tion between ADHD and ISU/SUDs, as ADHD is associ- with those without it (Figure 2). The heterogeneity among ated with school failure, impulsivity, and affiliation with studies was large (I2 = 55%). groups of deviant peers (Marshal et al., 2003), and might be The presence of outlier results was investigated and related to vulnerability genes (Pato et al., 1993) that also there was one study (Szobot et al., 2007) which was respon- increase the susceptibility to SUDs. However, it should be sible for 18% of the heterogeneity. The pooled OR exclud- noted that, even though many of these studies were con- ing this study was 1.18 (95% CI = [0.83, 1.67], p = .35, I2 = ducted in large community samples, the number of individ- 37%). With the removal of this study, the power of the uals with ADHD in many of these samples was small and meta-analytical study dropped from 30% to 15%. the numbers were even smaller when dividing participants with ADHD according to the presence of comorbidity with CD. Therefore, the ability to detect moderate increases in Metaregression OR is impaired due to power issues. The metaregression was conducted without the outlier From this perspective, the meta-analytical technique study (Szobot et al., 2007). In the univariate model, of the employed here is particularly useful, by allowing for com- 19 variables tested, the factors associated with the variabil- bination of samples. It is noteworthy that, even though this ity of results among studies (p < .2) were nature of the meta-analysis was based on 15 published studies, with a sample (clinical or nonclinical), pharmacological treatment combined sample of more than 1,000 participants with of the sample, diagnostic instrument for the assessment of ADHD, we still did not have enough power to detect a sig- ADHD, status of the evaluator of SUDs (blind or not blind), nificant increase in chance of 1.35. This finding suggests and adjustment of the OR for socioeconomic status (SES). that, if any association between ADHD and ISU exists when In the multivariate model, adjustment of the OR by SES adjustment for CD is performed, it would not be a strong (p = .05) maintained statistical significance. In this case, one. studies that did not adjust for SES tend to find ORs smaller The review of the literature demonstrated a moderate than those that controlled for this variable. The meta- degree of inconsistency across studies reporting the associ- analytic result from studies that used a measure of ISU did ation between ADHD and ISU. The only variable that was not differ significantly from the results of studies that found to explain some of the heterogeneity among studies focused on SUDs. was adjustment for SES. This finding of the metaregression is unexpected given data indicating that both hyperactive/ impulsive symptoms and SUDs are related with a lower SES Discussion (Fergusson et al., 2007). ADHD is a highly prevalent mental disorder in childhood The above findings should be considered in the context and adolescence, with a worldwide prevalence estimated at of some limitations. First, although the main aim was to about 5% (Polanczyk, de Lima, Horta, Biederman, & analyze the association of ADHD with ISU, while control- Rohde, 2007). Its long-term impact on the subject, his or ling for CD, studies considered in the meta-analysis often her family, and society in general has been widely docu- reported measures for SUDs. Given the association between mented (Barkley, Murphy, & Fischer, 2008; Mannuzza SUDs and ISU and the greater clinical relevance of SUDs, et al., 1998). Although the association of ISU and/or SUDs we chose to include the measure for SUDs, rather than ISU, is widely acknowledged (Barkley et al., 2004; Fergusson whenever such a measure was available. It should be noted et al., 2007; Mannuzza et al., 1991), it is of paramount that the metaregression did not identify studying SUDs ver- importance to establish if ADHD implies a greater risk for sus studying ISU as a reason for discrepancy in the findings. ISU and SUDs when controlling for CD. Most individual Second, the electronic search was restricted to PubMed. studies that have controlled for CD suggest that such an However, due to the importance of the topic, we found it association does not exist. The meta-analysis performed highly unlikely that articles that addressed it would be pub- also does not confirm that ADHD increases the risk for lished in journals not indexed in this database. Third, the pos- ISU/SUDs if CD symptoms are controlled—although it sibility of investigating the relevance of different subtypes/ found an increase of 35% in the chance for ISU/SUDs in domains of ADHD, although compelling, was not possible participants with ADHD, the result was not statistically due to power limitations of the studies. Last, we cannot gen- significant. However, the power of this study, even when eralize results to trajectories of ISU and SUDs. This study

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Figure 2. Forest plot of ORs (and 95% CI) of illicit substance use from studies of ADHD versus non-ADHD, 1993-2007 Note: OR = odds ratio; CI = confidence interval.

only investigated the risk of occurrence of ISU or SUDs. It of the increase in chance indicated by this meta-analysis did not investigate the impact of ADHD on the course or suggests the need for very large samples to be able to inves- response to treatment, once ISU or even SUDs are installed. tigate thoroughly this association. Second, because of the Three studies (Burke et al., 2001; Hartsough & Lambert, difficulty of gathering samples of appropriate size to define 1987; Young et al., 2005) did not report SUD rates for indi- this issue, it is advisable that future studies address the pos- viduals with ADHD because they were not significant. sibility of an association between ADHD and ISU taking Authors of these studies were contacted, but this informa- into account a dimensional (rather than a categorical) analy- tion was not retrieved in two cases (Burke et al., 2001; sis, to increase their power. Hartsough & Lambert, 1987). This may have biased our It is also important to note that ISU and SUDs have a results. The tendency of not reporting negative findings is multifactorial etiology, comprising environmental (Callas, widespread through the medical literature (Sterne, Egger, & Flynn, & Worden, 2004) and biological factors (Kendler, Davey, 2001). However, it is impossible to estimate the Jacobson, Prescott, & Neale, 2003). Because of this multi- direction of this potential bias. The inclusion of these nega- factorial etiology, it is possible that results obtained from tive studies could either increase or decrease the signifi- samples of one country do not necessarily hold true for cance of the findings (i.e., ADHD as a risk factor for ISU) other countries or cultures. because taking advantage of an increased sample size, we automatically increase power, making CIs smaller. Acknowledgments Although the available data did not corroborate a signifi- The authors wish to acknowledge the cooperation of Drs John cant association between ADHD and ISU, further studies Horwood, David Fergusson, Jane Costello, Russell Barkley, should contemplate the investigation of ADHD as a risk Salvatore Mannuzza, Marijke Hofstra, Jan van der Ende and Susan factor for ISU with certain precautions. First, the magnitude Young, who contributed with additional data on their samples.

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Authors’ Note References Data presented as a poster presentation in the 1st ADHD interna- American Psychiatric Association. (1994). Diagnostic and statis- tional conference in Amsterdam, 2010. tical manual of mental disorders (4th ed.). Washington, DC: Dr. Young has been consultant for Janssen-Cilag, Eli-Lilly, and Author. Shire. Dr. Young has given educational talks at meetings sponsored August, G. J., Winters, K. C., Realmuto, G. M., Fahnhorst, T., by Janssen-Cilag, Shire, Novartis, Eli-Lilly, and Flynn-Pharma. Botzet, A., & Lee, S. (2006). Prospective study of adoles- Dr. Young has received research grants from Janssen-Cilag and cent drug use among community samples of ADHD and non- Eli-Lilly. Dr. Young was a member of the National Institute of ADHD participants. Journal of the American Academy of Health and Clinical Excellence (NICE) guideline development Child & Adolescent Psychiatry, 45, 824-832. group for ADHD. Dr. Barkley has received funding in the previous year from Commonwealth of Massachusetts—retirement Barkley, R. A., Anastopoulos, A. D., Guevremont, D. C., & pension from University of MA Medical School; Eli-Lilly Co. Fletcher, K. E. (1991). Adolescents with ADHD: Patterns of (consultant, speaker, expert witness fees); Janssen-Cilag and behavioral adjustment, academic functioning, and treatment Janssen-Ortho (speaker fees); McNeil Pharmaceuticals (United utilization. Journal of the American Academy of Child & Ado- States; speaker fees); Medice Pharmaceutical Co. (Germany; lescent Psychiatry, 30, 752-761. speaker fee); Novartis (Germany; speaker fee); Shire Pharmaceutical Barkley, R. A., Fischer, M., Edelbrock, C., & Smallish, L. (1990). Co. (consulting and speaker fees); Guilford Publications (book and The adolescent outcome of hyperactive children diagnosed newsletter royalties); Jones and Bartlett, Publishers (product royal- by research criteria: I. An 8-year prospective follow-up study. ties); J & K Seminars (speaker fees and product royalties); Journal of the American Academy of Child & Adolescent Psy- ContinuingEdCourses.com (online CEU course royalties); PESI. chiatry, 29, 546-557. com (speaker fees, product royalties). Dr. Sergeant is part of the Barkley, R. A., Fischer, M., Smallish, L., & Fletcher, K. (2004). advisory board of Eli-Lilly and Shire. Dr. Sergeant has also received research grants from Eli-Lilly and speaker’s fee from Shire, Eli- Young adult follow-up of hyperactive children: Antisocial Lilly, Janssen-Cillag, and Novartis. activities and drug use. Journal of Child Psychology and Psy- chiatry, 45, 198-211. Declaration of Conflicting Interests Barkley, R. A., Murphy, K. R., & Fischer, M. (2008). ADHD in The author(s) declared the following potential conflicts of inter- adults: What the science says. New York, NY: Guilford. est with respect to the research, authorship, and/or publication of Biederman, J., Monuteaux, M., Mick, E., Spencer, T., Wilens, T., this article: Luis Augusto Rohde has served as a speaker and/or Klein, K., . . . Faraone, S. (2006). Psychopathology in females consultant for Eli-Lilly, Janssen-Cilag, and Novartis in the last 5 with attention-deficit/hyperactivity disorder: A controlled, five- years. Currently, his only industry-related activity is taking part year prospective study. Biological Psychiatry, 60, 1098-1105. in the advisory board/speakers’ bureau for Eli-Lilly, Novartis, Biederman, J., Wilens, T., Mick, E., Spencer, T., & Faraone, S. and Shire (less than US$10,000 per year and reflecting less than (1999). Pharmacotherapy of attention-deficit/hyperactivity 5% of his gross income per year). The ADHD and Juvenile disorder reduces risk for substance use disorder. Pediatrics, Bipolar Disorder Outpatient Programs chaired by him received 104, 20-24. unrestricted educational and research support from the following Bramham, J., Ambery, F., Young, S., Morris, R., Russell, A., pharmaceutical companies in the last 3 years: Abbott, Bristol- Xenitidis, K., . . . Murphy, D. (2009). Executive functioning Myers Squibb, Eli-Lilly, Janssen-Cilag, Novartis, and Shire. Paulo Mattos has served as a speaker for Novartis and Janssen- differences between adults with attention deficit hyperactivity Cilag in the last 5 years. He is part of the Advisory Board of disorder and autistic spectrum disorder in initiation, planning Novartis and Janssen-Cilag and received research support from and strategy formation. Autism, 13, 245-264. Janssen-Cilag in 2008. Isabella Souza served as a speaker for Burke, J., Loeber, R., & Lahey, B. (2001). Which aspects of Novartis and Janssen-Cilag in 2009. ADHD are associated with tobacco use in early adolescence? Journal of Child Psychology and Psychiatry, 42, 493-502. Funding Burns, G. L., & Walsh, J. A. (2002). The influence of ADHD- The author(s) disclosed receipt of the following financial hyperactivity/impulsivity symptoms on the development of support for the research, authorship, and/or publication of this oppositional defiant disorder symptoms in a 2-year longitudinal article: Maria Antonia Serra-Pinheiro received funding from the study. Journal of Abnormal Child Psychology, 30, 245-256. Brazilian scientific research agency to sponsor her work. Callas, P. W., Flynn, B. S., & Worden, J. K. (2004). Potentially modifiable psychosocial factors associated with alcohol use Note during early adolescence. Addictive Behaviors, 29, 1503-1515. 1. AND means that the subjects were considered ADHD patients Charach, A., Yeung, E., Climans, T., & Lillie, E. (2011). Childhood in those studies only if both teacher and parents provided informa- attention-deficit/hyperactivity disorder and future substance tion that would corroborate that diagnosis. OR means that subjects use disorders: Comparative meta-analyses. Journal of the in those studies were considered ADHD if either teacher of parent American Academy of Child & Adolescent Psychiatry, 5, 9-21. corroborated the diagnosis.

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Bios Dídia Fortes is a psychiatrist and researcher at the Attention Deficit Research Group of the Federal University at Rio de Janeiro. Maria Antonia Serra-Pinheiro is a psychiatrist, working and conducting research in the area of ADHD. She has a MD and a Catia Araújo is a clinical psychologist in the Brazilian National PhD from the Federal University at Rio de Janeiro and is the Institute of Cancer, MSc in Computer Sciences, expert in President of CIPIA, an NGO devoted to care and education in the Neuropsychology, having worked with a multidisciplinary team area of child psychiatry. for more than 10 years in the Health and Education areas.

Evandro S. F. Coutinho has a PhD in Public Health at Federal Claudia M. Szobot is a child psychiatrist and she has a MD and University of Bahia-Brazil/London School of Hygiene and a PhD in Psychiatry from the Federal University at Rio Grande do Tropical Medicine-UK. Senior Researcher in Epidemiology - Sul. She has published mainly in the area of ADHD and substance Oswaldo Cruz Foundation - Brazil. Editor of the Cochrane use disorders. Schizophrenia Group since 1998. Luis A. Rohde is a Psychiatry professor at the Federal University Isabella S. Souza is a psychiatrist. She has a MD and a PhD from of Rio Grande do Sul. He has and MD and a PhD and is the head the Federal University of Rio de Janeiro. She is a researcher at the of the ADHD research group of the Federal University of Rio Attention Deficit Disorders group of the Federal University of Rio Grande do Sul. de Janeiro. Paulo Mattos is an adjunct professor at the Federal University of Camilla Pinna is a psychiatrist and researcher at the Attention Rio de Janeiro. He is a psychiatrist, has and MD, PhD and Post- Deficit Research Group of the Federal University at Rio de Doctorate title. He is the head of the Attention Deficit Research Janeiro. Group of the Federal University at Rio de Janeiro.

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