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Editorial
Published Online: 1 May 2008

Does Childhood Treatment of ADHD With Stimulant Medication Affect Substance Abuse in Adulthood?

One of the most controversial issues in childhood psychiatry is whether the widespread use of stimulant medications to treat children with attention deficit hyperactivity disorder (ADHD) increases the risk of substance abuse in adulthood. Part of the rationale for this concern is that stimulant medications (methylphenidate and amphetamine) share with drugs of abuse the ability to increase dopamine concentration in the nucleus accumbens, which is the neural mechanism considered crucial for their reinforcing effects (1) . Indeed, methylphenidate and amphetamine are sometimes abused in some settings (2) . This misuse can produce dependence. Another reason for concern is the timing of exposure. Human epidemiological studies have shown that the earlier an individual is exposed to substances with abuse potential, such as alcohol and nicotine, the greater the risk of drug abuse and dependence in adulthood (3) . However, the opposite perspective has also been proposed—that stimulant treatment of children and adolescents with ADHD may reduce the risk of later substance abuse (4) . Considering that individuals with ADHD are at higher-than-normal risk for substance abuse (5), it is urgent that these two perspectives be addressed properly, yet relatively few clinical studies have done so.
Two articles in this issue of the Journal provide new clinical evidence pertaining to these viewpoints, based on findings from prospective observational studies. One study, conducted by Biederman et al. (6), compares subgroups of children with ADHD who received treatment with stimulants in childhood or adolescence with those who did not. Another study, conducted by Mannuzza et al. (7), evaluates the age when stimulant treatment was initiated in childhood and its relationship to drug abuse in adulthood. The study also compares the prevalence of substance abuse in persons with ADHD with a comparison group. Both studies document high rates (up to 45%) of substance use disorders in their adult cohorts, but both conclude that the long-established clinical practice of the use of stimulant medication to treat young children with ADHD does not affect—neither increasing nor decreasing—the risk for substance abuse in adulthood.
Because of the relevance of these findings to clinical practice, it is important to identify potential sources of uncertainty. These two studies evaluated clinically referred samples, and medication status was not randomized, making the findings vulnerable to referral bias. The samples were also small, especially for the subgroup untreated with stimulants. Also, treatment with stimulants was initiated (as usual) at an average age between 8 and 9 years, with most children discontinuing treatment after an average of 2 (7) to 6 years (6) . Thus, most individuals were probably exposed to stimulants only a short time during childhood, and only a few were likely exposed to stimulants because of treatment during adolescence. Since preclinical studies revealed that exposure to stimulant drugs during the period corresponding with adolescence, but not in the period corresponding with childhood, increased sensitivity to the rewarding effects of cocaine (8), prospective studies of larger samples of adolescents treated with stimulant medications are necessary in order to more carefully evaluate the consequences of stimulant exposure during this developmental period. Studies in progress, such as the Multimodal Treatment Study of ADHD, which have larger samples of ADHD individuals and larger subgroups with extended or no treatment with stimulants throughout childhood and adolescence (9), will provide additional data on adult substance abuse outcomes.
An interesting finding of the Biederman et al. study is the failure to confirm the prior claim that treatment with stimulants markedly reduced the risk for substance abuse (4) . They suggest that the prior finding was because of a temporary benefit that delayed the initiation of drug abuse. This merits further investigation, since reduction of drug exposure during this developmental stage would be expected to result in an improvement in outcomes, including less risk for dependence. However, others have proposed a parsimonious explanation that the untreated ADHD group was an average of 2 years older than the treated group and that an uncontrolled age difference accounted for the difference in substance use that increased with age during adolescence (10) .
An interesting finding from the study by Mannuzza et al. is their observation that subjects with late initiation of stimulant medication (ages 8 to 12) had greater substance abuse that was mediated by an increase in antisocial personality disorder in adulthood. Remarkably, the subgroup with early treatment (before the age of 8) did not differ from comparison subjects in lifetime rates of non-alcohol substance use (27% versus 29%, respectively). The authors discuss the possibility that early stimulant treatment of ADHD may have a protective effect toward the emergence of conduct disorder, which usually precedes antisocial personality disorder and increases the risk for drug abuse. However, this hypothesis is not supported by early findings from the Multimodal Treatment Study of ADHD, in which treatment with stimulants in this prospective follow-up study did not selectively reduce conduct disorder (9), or by national trends over the past decade, when there has been a dramatic fivefold increase in the treatment of ADHD children in the United States with stimulants but no change in the prevalence of conduct disorder (11) .
The two articles in this issue highlight the need to develop a better understanding of the natural history of ADHD over time. It was once assumed that ADHD was a childhood disorder and that most children with childhood diagnoses of ADHD would outgrow their symptoms after puberty. Later, this idea was rejected, and it was proposed that ADHD will persist in a large number of individuals, ranging from 35%–60% of cases, depending on the diagnostic criteria used for the original sample (12) . Thus, an important question is whether these two trajectories—symptoms completely outgrown by adulthood versus a continued subset of symptoms—have a different neurobiology and whether they have different vulnerabilities for substance abuse disorders and long-term effects of treatment with stimulant medications.
A fundamental question is why there is such a high comorbidity between ADHD and substance abuse. There is evidence of impaired brain dopamine activity in individuals with ADHD (13), which could explain why individuals with ADHD are at greater risk of abusing drugs, since drugs of abuse acutely but temporarily raise the concentration of dopamine in the brain and could temporarily improve ADHD symptoms. In contrast, chronic drug abuse decreases dopamine brain activity (13) . Inasmuch as dopamine modulates the activity of brain regions (including the prefrontal cortex, striatum, hippocampus, and amygdala) implicated in the symptoms observed in ADHD, i.e., attention, executive function, and impulsivity (14), chronic drug exposure in ADHD individuals could exacerbate the symptoms of the disorder.
In these studies of the long-term outcomes of individuals with ADHD, the evidence that current clinical practice does not increase later substance use or abuse is comforting, but the failure to document that childhood treatment with stimulant medication decreases the high risk of substance abuse in adulthood is distressing. This highlights the need for the development of integrated treatments that target both ADHD and substance abuse in order to go beyond standard treatment and find a way to reduce or prevent substance abuse and provide better treatment if these disabling outcomes emerge.

Footnotes

Address correspondence and reprint requests to Dr. Volkow, National Institute on Drug Abuse, 6001 Executive Blvd., Rm. 5274, MSC 9581, Bethesda, MD 20892-9581; [email protected] (e-mail). Editorial accepted for publication February 2008 (doi: 10.1176/appi.ajp.2008.08020237).
Dr. Volkow reports no competing interests. Dr. Swanson has received speakers bureau honoraria from UCB, Janssen, and McNeil; he has received advisory board payment from UCB, Eli Lilly, and Shire; he has received research grants from McNeil; and he has received travel payment from UCB, Janssen, McNeil, Eli Lilly, and Shire. Dr. Freedman has reviewed this editorial and found no evidence of influence from their relationship.

References

1.
Wise RA: Brain reward circuitry: insights from unsensed incentives. Neuron 2002; 36:229–240
2.
Volkow ND, Swanson JM: Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD. Am J Psychiatry 2003; 160:1909–1918
3.
Grant BF, Dawson DA: Age at onset of alcohol use and its association with DSM-IV alcohol abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. J Subst Abuse 1997; 9:103–110
4.
Wilens TE, Faraone SV, Biederman J, Gunawardene S: Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature. Pediatrics 2003; 111:179–185
5.
Elkins IJ, McGue M, Iacono WG: Prospective effects of attention-deficit/hyperactivity disorder, conduct disorder, and sex on adolescent substance use and abuse. Arch Gen Psychiatry 2007; 64:1145–1152
6.
Biederman J, Monuteaux MC, Spencer T, Wilens TE, MacPherson HA, Faraone SV: Stimulant therapy and risk for subsequent substance use disorders in male adults with ADHD: a naturalistic controlled 10-year follow-up study. Am J Psychiatry 2008; 165:597–603
7.
Mannuzza S, Klein RG, Truong NL, Moulton JL III, Roizen ER, Howell KH, Castellanos FX: Age of methylphenidate treatment initiation in children with ADHD and later substance abuse: prospective follow-up into adulthood. Am J Psychiatry 2008; 165:604–609
8.
Volkow ND, Insel TR: What are the long-term effects of methylphenidate treatment? Biol Psychiatry 2003; 54:1307–1309
9.
Molina BS, Flory K, Hinshaw SP, Greiner AR, Arnold LE, Swanson JM, Hechtman L, Jensen PS, Vitiello B, Hoza B, Pelham WE, Elliott GR, Wells KC, Abikoff HB, Gibbons RD, Marcus S, Conners CK, Epstein JN, Greenhill LL, March JS, Newcorn JH, Severe JB, Wigal T: Delinquent behavior and emerging substance use in the MTA at 36 months: prevalence, course, and treatment effects. J Am Acad Child Adolesc Psychiatry 2007; 46:1028–1040
10.
Pelham WE: ADHD treatment with stimulant medication and later substance use, in Proceedings of the 51st Annual Meeting of the American Academy of Child and Adolescent Psychiatry. Washington, DC, AACAP, 2004
11.
Costello EJ, Foley DL, Angold A: 10-year research update review: the epidemiology of child and adolescent psychiatric disorders, II: developmental epidemiology. J Am Acad Child Adolesc Psychiatry 2006; 45:8–25
12.
Kessler RC, Adler LA, Barkley R, Biederman J, Conners CK, Faraone SV, Greenhill LL, Jaeger S, Secnik K, Spencer T, Ustün TB, Zaslavsky AM: Patterns and predictors of attention-deficit/hyperactivity disorder persistence into adulthood: results from the National Comorbidity Survey Replication. Biol Psychiatry 2005; 57:1442–1451
13.
Volkow ND, Wang GJ, Newcorn J, Telang F, Solanto MV, Fowler JS, Logan J, Ma Y, Schulz K, Pradhan K, Wong C, Swanson JM: Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/ hyperactivity disorder. Arch Gen Psychiatry 2007; 64:932–940
14.
Sonuga-Barke EJ: The dual pathway model of AD/HD: an elaboration of neuro-developmental characteristics. Neurosci Biobehav Rev 2003; 27:593–604

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Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 553 - 555
PubMed: 18450933

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Published online: 1 May 2008
Published in print: May, 2008

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James M. Swanson, Ph.D.

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