There is great clinical, research, and public health value to building a better understanding of the link between substance use disorders (SUD) and attention-deficit/hyperactivity disorder (ADHD).1,2 Because ADHD is highly prevalent, onsets in early childhood, persists into adolescence and adulthood, and has overlapping symptoms, risks, and outcomes with SUD, elucidating the interaction and treatment of the two disorders is extremely valuable.
Substance Use Disorder
ADHD is among the most prevalent neurobehavioral disorders affecting between 6% and 9% of children and 5% of adults.2 Likewise, SUD is common with 10% of adolescents and 20% to 30% of adults meeting criteria for a SUD at some point in their life.3 SUD is linked with several negative outcomes that encompass multiple aspects of life and are exacerbated by early onset of SUD, such as risky behaviors, suicidality, and academic and occupational underachievement.4 SUDs have been linked to many comorbid psychiatric disorders, and large-scale epidemiologic surveys have reported a connection to ADHD, mood and anxiety disorders, and other psychopathology. Among overlaps with SUD, ADHD has been of great interest and provides some of the most compelling indications of bidirectionality.5
Bidirectional Overlap of ADHD and SUD
Because ADHD first presents in early childhood, it generally precedes SUD, and thus provides a unique perspective from which to investigate directionality of the two disorders. Data suggest that youth with ADHD are approximately 2 to 3 times more likely to develop cigarette smoking and/or SUD compared to their peers without ADHD,2,6 and even further magnified when coinciding with conduct or mood disorders. Similarly, studies show ADHD to be linked with an earlier onset, longer course, and more severe form of cigarette smoking and/or SUD.7
Conversely, high rates of ADHD have been reported in adolescent and adult samples of SUD. For instance, in the Cannabis Youth Treatment Study, ADHD was the second most common comorbidity reported in 38% of 600 adolescents.8 Similarly, meta-analytic findings5 suggest that nearly one-quarter of adult SUD patients also have ADHD. Despite these findings, ADHD continues to be underidentified in addiction treatment settings.
The ADHD and SUD Connection
It remains unclear whether ADHD and SUD are primarily linked by psychosocial, biologic, or a combination of both factors. A psychosocial link has been explained by a developmental progression in which ADHD causes academic and social difficulties and discouragement, culminating in conduct disorder, disobedient behavior, and substance use.9 Additionally, ADHD may lead to substance use problems via “self-medication.”10 Abnormalities in the dopaminergic system and striatal involvement4,11 have been implicated in both disorders. Conceptually, Adisetiyo and Gray12 suggest that reduced (pre)frontal cortical inhibitory oversight of the dysregulated motivation-reward processing brain network in ADHD patients might result in an asymmetry leading to excessive cigarette and substance use. Other factors, such as familial and genetic contributions, like prenatal exposure to parental substance use, have also been shown to potentially play a role in the association between ADHD and SUD.13
Effects of Early Pharmacological Treatment for ADHD on Later SUD Risk
The literature is less controversial as it relates to the early treatment of ADHD with stimulants and the subsequent reduction in the risk for later SUD. Prospective medication trials show that stimulant treatment in adolescence reduces the subsequent risk of cigarette smoking and SUD.14,15 For instance, a 3-year follow-up of a 52-week methylphenidate trial showed reduced substance misuse in patients who were treated.15 Interestingly, earlier meta-analyses incorporating relatively small clinical studies showed only a protective or negligible effect on future development of SUD.16,17 However, subsequent data from much larger population-based studies support a protective effect. For instance, as part of the large Swedish registry studies, Chang et al.18 compared ADHD patient medication status in 2006 with their SUD status in 2009 and found that among 26,249 men and 12,504 women with ADHD, 16% and 10.4%, respectively, were taking stimulant medication in 2006. In 2009, the medicated group showed a 31% reduction in SUD and an overall reduction of SUD by 13% for each year of medication status.18 In a review of almost 3 million adolescent and adult patients in the United States, Quinn et al.19 found that while receiving ADHD medication, men had a 35% reduction in substance-related events compared to nonmedicated periods. McCabe et al.20 reported that in a survey of 40,358 high school seniors, earlier onset and longer duration of stimulant treatment reduced the likelihood of substance use in adolescence compared to patients with later onset and shorter duration use. In fact, youth whose stimulants were initiated prior to age 9 years and treated chronically had similar substance use patterns as population controls. Furthermore, in a separate survey of 4,755 high schoolers, McCabe et al.21 also reported the lower likelihood of substance use and related problems in students with earlier medical use of stimulants, and inversely, found a greater likelihood of substance use and related problems in students who did not take stimulant medication.
Diagnostic clarity of ADHD is often compromised when patients present with SUD. Accurately diagnosing adolescents and young adults with ADHD requires the review of past performance, testing, and medical review, as well as consideration of self, parent, and teacher-reported ADHD rating scales. However, active SUD may exacerbate ADHD symptoms as the problematic use of substances could lead to behavioral and functioning deficits that mirror ADHD. Due to the potential overlap of SUD and ADHD symptoms, we recommend a brief period of abstinence or reduced substance use prior to establishing a new diagnosis. Crunelle et al.22 emphasize the need for ADHD screening in SUD populations in a recent international statement on the treatment of comorbid SUD and ADHD.
When treating SUD in patients with ADHD, symptoms of both disorders must be addressed (Table 1). Moreover, attention needs be paid to enhancing engagement and retention, mitigating SUD, and addressing ADHD. Our own group and others23 recommend a psychotherapy regimen that commences with motivational interviewing with later sessions focusing on standard cognitive-behavioral therapy (CBT) directed initially at SUD and then ADHD. It is notable, however, that just using CBT in patients with severe ADHD and SUD may be insufficient as it has been associated with early drop-out from treatment,23 highlighting the need to consider adjunct pharmacotherapy in the treatment.
Strategies for Treating Substance Use Disorder in ADHD
Although a large extant literature supports the use of medications for ADHD, there is less evidence of the efficacy of medication in patients with SUD and ADHD. Older studies targeting these patients suggest that pharmacotherapy results in a mild to negligible decrease in ADHD symptoms with a more variable effect on substance use.24 However, more recent data using higher stimulant dosing for ADHD support a positive effect in reducing both ADHD and SUD outcomes. Levin et al.25 in a randomized controlled trial with adults with ADHD and cocaine use disorders, reported reductions in both ADHD and SUD in the groups receiving 60 and 80 mg of extended-release mixed amphetamine salts compared to placebo. In a naturalistic, long-term (average = 18.4 months) follow-up study of 60 men with ADHD and comorbid severe SUD, the group medicated for ADHD had fewer SUD relapses, less need for compulsory care, and were more successful in housing and employment.26 Likewise, Konstenius et al.27 found that formerly incarcerated people with ADHD and amphetamine dependence, receiving high-dose osmotic release oral methylphenidate (up to 180 mg/day) had reductions in ADHD, SUD, and missed visits compared to placebo.27 The nonstimulant atomoxetine has also been shown to be effective in reducing ADHD and periods of heavy drinking in people who have recently been abstaining from alcohol; however, the nonstimulant was not associated with lower rates of relapse.28 It is notable that in these and other studies, no substantial adverse effects have been reported with the various ADHD medications in relation to substance use. Clearly more work is needed to understand various factors (ie, ADHD severity, psychiatric comorbidity) in future studies to improve the ability to best prescribe appropriate pharmacotherapy in clinical practice.29
Clinical Recommendations for Safe Prescribing of Stimulants
There is a growing body of literature documenting the nonmedical use and diversion of stimulants among college-aged people, with clear short- and longer-term consequences.30 Studies indicate that college campuses have concerning rates of stimulant misuse, ranging from 8% to 34%.31 These rates are magnified depending on the specific student population. For example, rates increase when SUD is in the clinical typography, and in college students who are members of social fraternities and sororities, rates of stimulant misuse have been found to be over 50%.31,32 Furthermore, misusers report easily procuring stimulants for nonmedical purposes, and report perceiving misuse as widespread and not being associated with negative consequences to physical or mental health.32 This is of concern given our recent work in which we found that more than one-third of misusers met criteria for either threshold or subthreshold stimulant use disorder and half met criteria for a SUD.33 These data suggest that nonmedical stimulant use may not be an isolated occurrence or inconsequential scenario, and more frequently occurs in people with SUD.
In the case of patients with SUD, practitioners should consider precautions in choosing the type and preparation of medication for ADHD. Nonstimulants (atomoxetine, bupropion, and tricyclic antidepressants) are useful to begin treatment due to their lack of abuse liability and demonstrated efficacy in ADHD (and/or SUD) and comorbid conditions. Stimulants remain the most efficacious in reducing ADHD symptoms with general safety even in the context of SUD. Long-acting preparations are clearly the preferred form of stimulants in higher-risk groups such as people with SUD, which is not only related to their lower abuse liability,33 but also relieving ADHD symptoms throughout the day. Practitioners should routinely educate the patient and family/caregivers about the ethical/legal consequences of stimulant misuse and diversion, the safe storage of stimulants (eg, avoid medicine cabinets), and clearly articulate guidelines on premature refill requests.
Clinicians, researchers, and public health officials continue to be greatly interested in the overlap between SUD and ADHD. Studies have demonstrated that ADHD increases the risk of cigarette smoking and SUD and that up to one-half of adults and adolescents with SUD have ADHD.5,7,8 Although still inconclusive, evidence suggests these disorders are linked via various factors, including behavioral, biologic, and genetic. Early pharmacotherapy of ADHD does not increase SUD; conversely, recent studies14,15,20 suggest that it substantially reduces cigarette smoking and SUD and that early duration onset of stimulant treatment is associated with the best outcomes. In patients with comorbid SUD and ADHD, treatment of both disorders is recommended. Structured therapies such as CBT appear helpful with adjunct nonstimulants and extended-release stimulants (perhaps requiring higher stimulant dosing). More research is necessary to further elucidate the mechanism of overlap between these disorders to improve prevention and treatment of SUD in people with ADHD.
- Carrellas N, Wilens TE, Anselmo R. Treatment of comorbid substance use disorders and ADHD in youth. Curr Treat Options Psychiatry. 2016;3(1):15–27. doi:. doi:10.1007/s40501-016-0072-y [CrossRef]
- Wilens TE, Martelon M, Joshi G, et al. Does ADHD predict substance-use disorders? A 10-year follow-up study of young adults with ADHD. J Am Acad Child Adolesc Psychiatry. 2011;50(6):543–553. doi:. doi:10.1016/j.jaac.2011.01.021 [CrossRef]
- Merikangas KR, McClair VL. Epidemiology of substance use disorders. Hum Genet. 2012;131(6):779–789. doi:. doi:10.1007/s00439-012-1168-0 [CrossRef]
- Volkow ND, Koob GF, McLellan AT. Neurobiologic advances from the brain disease model of addiction. N Engl J Med. 2016;374(4):363–371. doi:. doi:10.1056/NEJMra1511480 [CrossRef]
- van Emmerik-van Oortmerssen K, van de Glind G, van den Brink W, et al. Prevalence of attention-deficit hyperactivity disorder in substance use disorder patients: a meta-analysis and meta-regression analysis. Drug Alcohol Depend. 2012;122(1–2):11–19. doi:. doi:10.1016/j.drugalcdep.2011.12.007 [CrossRef]
- Charach A, Yeung E, Climans T, Lillie E. Childhood attention-deficit/hyperactivity disorder and future substance use disorders: comparative meta-analyses. J Am Acad Child Adolesc Psychiatry. 2011;50(1):9–21. doi:. doi:10.1016/j.jaac.2010.09.019 [CrossRef]
- Wilens TE, Biederman J, Mick E, Faraone SV, Spencer T. Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders. J Nerv Ment Dis.1997;185(8):475–482. doi:10.1097/00005053-199708000-00001 [CrossRef]
- Dennis M, Godley SH, Diamond G, et al. The Cannabis Youth Treatment (CYT) Study: main findings from two randomized trials. J Subst Abuse Treat. 2004;27(3):197–213. doi:. doi:10.1016/j.jsat.2003.09.005 [CrossRef]
- Mannuzza S, Gittelman-Klein R, Konig PH, Giampino TL. Hyperactive boys almost grown up: IV. Criminality and its relationship to psychiatric status. Arch Gen Psychiatry. 1989;46:1073–1079. doi:10.1001/archpsyc.1989.01810120015004 [CrossRef]
- Wilens T, Adamson J, Sgambati S, et al. Do individuals with ADHD self-medicate with cigarettes and substances of abuse? Results from a controlled family study of ADHD. Am J Addict. 2007;16(suppl 1):14–23. doi:. doi:10.1080/10550490601082742 [CrossRef]
- van Wingen GA, van den Brink W, Veltman DJ, et al. Reduced striatal brain volumes in non-medicated adult ADHD patients with comorbid cocaine dependence. Drug Alcohol Depend. 2013;131(3):198–203. doi:. doi:10.1016/j.drugalcdep.2013.05.007 [CrossRef]
- Adisetiyo V, Gray KM. Neuroimaging the neural correlates of increased risk for substance use disorders in attention-deficit/hyperactivity disorder--a systematic review. Am J Addict. 2017;26(2):99–111. doi:. doi:10.1111/ajad.12500 [CrossRef]
- Zhu JL, Olsen J, Liew Z, Li J, Niclasen J, Obel C. Parental smoking during pregnancy and ADHD in children: the Danish National Birth Cohort. Pediatrics. 2014;134(2):e382–e388. doi:. doi:10.1542/peds.2014-0213 [CrossRef]
- Hammerness P, Joshi G, Doyle R, et al. Do stimulants reduce the risk for cigarette smoking in youth with attention-deficit hyperactivity disorder? A prospective, long-term, open-label study of extended-release methylphenidate. J Pediatr. 2013;162(1):22–27.e2. doi:. doi:10.1016/j.jpeds.2012.06.046 [CrossRef]
- Ginsberg Y, Langstrom N, Larsson H, Lindefors N. Long-term treatment outcome in adult male prisoners with attention-deficit/hyperactivity disorder: three-year naturalistic follow-up of a 52-week methylphenidate trial. J Clin Psychopharmacol. 2015;35(5):535–543. doi:. doi:10.1097/JCP.0000000000000395 [CrossRef]
- Wilens T, Faraone S, Biederman J, Gunawardene S. Does stimulant therapy of ADHD beget later substance abuse: a metanalytic review of the literature. Pediatrics. 2003;11(1):179–185. doi:10.1542/peds.111.1.179 [CrossRef]
- Humphreys KL, Eng T, Lee SS. Stimulant medication and substance use outcomes: a meta-analysis. JAMA Psychiatry. 2013;70(7):740–749. doi:. doi:10.1001/jamapsychiatry.2013.1273 [CrossRef]
- Chang Z, Lichtenstein P, Halldner L, et al. Stimulant ADHD medication and risk for substance abuse. J Child Psychol Psychiatry. 2014;55(8):878–885. doi:. doi:10.1111/jcpp.12164 [CrossRef]
- Quinn PD, Chang Z, Hur K, et al. ADHD medication and substance-related problems. Am J Psychiatry. 2017;174(9):877–885. doi:. doi:10.1176/appi.ajp.2017.16060686 [CrossRef]
- McCabe SE, Dickinson K, West BT, Wilens TE. Age of onset, duration, and type of medication therapy for attention-deficit/hyperactivity disorder and substance use during adolescence: a multi-cohort national study. J Am Acad Child Adolesc Psychiatry. 2016;55(6):479–486. doi:. doi:10.1016/j.jaac.2016.03.011 [CrossRef]
- McCabe SE, Veliz P, Boyd CJ. Early exposure to stimulant medications and substance-related problems: the role of medical and nonmedical contexts. Drug Alcohol Depend. 2016;163:55–63. doi:. doi:10.1016/j.drugalcdep.2016.03.019 [CrossRef]
- Crunelle CL, van den Brink W, Moggi F, et al. International Consensus Statement on Screening, Diagnosis and Treatment of Substance Use Disorder Patients with Comorbid Attention Deficit/Hyperactivity Disorder. Eur Addict Res. 2018;24(1):43–51. doi:. doi:10.1159/000487767 [CrossRef]
- van Emmerik-van Oortmerssen K, Vedel E, van den Brink W, Schoevers RA. Integrated cognitive behavioral therapy for patients with substance use disorder and comorbid ADHD: two case presentations. Addict Behav. 2015;45:214–217. doi:. doi:10.1016/j.addbeh.2015.01.040 [CrossRef]
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- Levin FR, Mariani JJ, Specker S, et al. Extended-release mixed amphetamine salts vs placebo for comorbid adult attention-deficit/hyperactivity disorder and cocaine use disorder: a randomized clinical trial. JAMA Psychiatry. 2015;72(6):593–602. doi:. doi:10.1001/jamapsychiatry.2015.41 [CrossRef]
- Bihlar Muld B, Jokinen J, Bolte S, Hirvikoski T. Long-term outcomes of pharmacologically treated versus non-treated adults with ADHD and substance use disorder: a naturalistic study. J Subst Abuse Treat. 2015;51:82–90. doi:. doi:10.1016/j.jsat.2014.11.005 [CrossRef]
- Konstenius M, Jayaram-Lindstrom N, Guterstam J, Beck O, Philips B, Franck J. Methylphenidate for attention deficit hyperactivity disorder and drug relapse in criminal offenders with substance dependence: a 24-week randomized placebo-controlled trial. Addiction. 2014;109(3):440–449. doi:. doi:10.1111/add.12369 [CrossRef]
- Wilens TE, Adler LA, Weiss MD, et al. Atomoxetine treatment of adults with ADHD and comorbid alcohol use disorders. Drug Alcohol Depend. 2008;96(1–2):145–154. doi:. doi:10.1016/j.drugalcdep.2008.02.009 [CrossRef]
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Strategies for Treating Substance Use Disorder in ADHD
|Assessment||Evaluate SUD, ADHD, and other comorbidities|
|In context to SUD||ADHD treatment should be considered|
|Substance use, misuse, or less severe SUD with ADHD||Initiate or maintain ADHD treatment concomitantly (CBT, nonstimulants, stimulants)|
|For more severe SUD with ADHD||Address SUD initially (may require discontinuing ongoing ADHD treatment)|
|If unable to address SUD initially or if recalcitrant SUD in ADHD||For ADHD use CBT and nonstimulants initially, then consider extended-release stimulants (avoid immediate-release stimulants)|