Journal of Attention Disorders http://jad.sagepub.com/ 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 The online version of this article can be found at: http://jad.sagepub.com/content/early/2012/02/15/1087054711435362 Published by: http://www.sagepublications.com Additional services and information for Journal of Attention Disorders can be found at: Email Alerts: http://jad.sagepub.com/cgi/alerts Subscriptions: http://jad.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav >> OnlineFirst Version of Record - Feb 17, 2012 What is This? Downloaded from jad.sagepub.com at CAPES on February 27, 2012 JADXXX10.1177/1087054711435362Ser 435362ra-Pinheiro et al.Journal of Attention Disorders © 2012 SAGE Publications Reprints and permission: sagepub.com/journalsPermissions.nav 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] Downloaded from jad.sagepub.com at CAPES on February 27, 2012 2 Journal of Attention Disorders XX(X) 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