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Cited by 211Attention Deficit Hyperactivity DisorderSubstance Abuse Treatment and OutcomesNeurotransmitter Receptor Influence on Behavior

Stimulant Medication and Substance Use Outcomes

Open access
Humphreys, Kathryn L., Eng, Timothy, Lee, Steve S.·2013·JAMA Psychiatry
DOI 10.1001/jamapsychiatry.2013.1273PMC PMC6688478
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Abstract

Meta-analysis of longitudinal studies of childhood stimulant treatment and later substance outcomes.

Integrity signals

Registry

Crossref · 10.1001/jamapsychiatry.2013.1273

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 17 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The likelihood of substance initiation did not differ according to medication status.

    “this study suggests that the likelihood of substance initiation did not differ according to medication status.”
    Quote in the paperSubstantial claim
  • Findingown data

    The percentage of children with ADHD treated with stimulant medication was negatively associated with pooled effect size for alcohol abuse or dependence (t=-4.25, P=.003, adjusted R2=89.05).

    “The percentage of children with ADHD treated with stimulant medication (number who received medication/total number of children with ADHD) was negatively associated with pooled effect size (t = −4.25, P =.003, adjusted R2 = 89.05).”
    Quote in the paperSubstantial claim
  • Findingown data

    In this meta-analysis of longitudinal studies, children with ADHD who received stimulant medication and those who did not had comparable later outcomes for any substance use and for abuse or dependence across all substance types.

    “Results suggested comparable outcomes between children with and without cation treatment history for any substance use and abuse or dependence outcome across all substance types.”
    • Also stated in: § DISCUSSION · hedged
      “Across 5 types of substance (ie, alcohol, cocaine, marijuana, nicotine, and nonspecific drugs) for lifetime use and abuse or dependence, results indicated that substance outcomes were comparable to those individuals who did and did not receive medication.”
    Quote in the paperSubstantial claim
  • Findingown data

    For nicotine use, after removing the Huss study, effect sizes were no longer significantly heterogeneous (Q=4.29, P=.12).

    “For nicotine use, after the removal of Huss,32 the effect sizes were no longer significantly heterogeneous (Q = 4.29, P =.12).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Huss,32

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Findingown data

    When both alcohol abuse or dependence moderators were included in the same model, only the percentage treated remained a significant predictor of between-study variance.

    “When both moderators were in the same model, only the percentage treated remained a significant predictor of between-study variance.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 22
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 2

  • May combine two claims.

    Findingown data

    For marijuana abuse or dependence, the meta-analysis found comparable odds between medicated and nonmedicated children (OR, 0.97; 95% CI, 0.59-1.59; P=.87), with significant heterogeneity across studies.

    “The random-effects model estimated comparable odds of marijuana abuse or dependence for children who did vs did not receive medication (OR, 0.97; 95% CI, 0.59−1.59; P =.87); however, significant heterogeneity was observed across the studies (Q = 15.68, P=.047).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For lifetime alcohol use, the meta-analysis found no difference between children who received stimulant medication and those who did not (OR, 0.99; 95% CI, 0.61-1.62; P=.97), with no significant heterogeneity.

    “The random-effects meta-analysis found that children who did and did not receive medication treatment were comparable in alcohol use (OR, 0.99; 95% CI, 0.61−1.62; P =.97), and no significant heterogeneity was observed across studies (Q = 2.82, P =.42).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For alcohol abuse or dependence, the meta-analysis found comparable odds between medicated and nonmedicated children (OR, 0.80; 95% CI, 0.46-1.38; P=.42), with significant heterogeneity across studies.

    “The random-effects regression estimated that children with or without medication treatment were largely comparable to alcohol abuse or dependence (OR, 0.80; 95% CI, 0.46−1.38; P =.42), although significant variability was seen in effect sizes (Q = 33.87, P <.001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For cocaine abuse or dependence, the meta-analysis found comparable odds between medicated and nonmedicated children (OR, 1.10; 95% CI, 0.51-2.38; P=.81), with no significant heterogeneity.

    “the random-effects model estimated that children who received medication treatment were comparable to children who did not receive medication treatment in the development of cocaine abuse or dependence (OR, 1.10; 95% CI, 0.51−2.38; P =.81). No significant heterogeneity in ORs was noted (Q = 8.17, P =.23).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    When the Wilens et al study was removed, nonspecific drug abuse or dependence showed no significant heterogeneity and an estimated effect of 1.01 (95% CI, 0.70-1.44), suggesting that study contributed to the heterogeneous pooled effect.

    “When the model was reanalyzed with the study by Wilens et al36 removed, no significant heterogeneity was found, and the estimated effect was 1.01 (95% CI, 0.70−1.44), suggesting that the study by Wilens et al36 contributed to the heterogeneous pooled effect size.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wilens et al36

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingown data

    For nonspecific drug abuse or dependence, the meta-analysis found comparable outcomes between medicated and nonmedicated children (OR, 0.85; 95% CI, 0.51-1.40; P=.52), with significant heterogeneity.

    “The random-effects model for all studies estimated that children who received medication treatment were comparable to those who did not (OR, 0.85; 95% CI, 0.51−1.40; P =.52), although once again significant heterogeneity was observed (Q = 15.99, P =.01).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For ever having used nicotine, the meta-analysis found largely comparable outcomes between medicated and nonmedicated children, with limited precision (OR, 1.55; 95% CI, 0.73-3.30; P=.26) and significant heterogeneity.

    “the random-effects model estimated that children with ADHD who received stimulant medication were largely comparable to children not treated with stimulant medication, although the precision of the estimate is limited (OR, 1.55; 95% CI, 0.73−3.30; P =.26). However, there was evidence of significant heterogeneity (Q = 10.72, P =.01).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For marijuana abuse or dependence, leave-one-out pooled odds ratios ranged from 0.96 to 1.23, all confidence intervals included 1, and heterogeneity resolved after removing three studies.

    “For marijuana abuse or dependence, pooled OR estimates ranged from 0.96 to 1.23, and all 95% CIs included 1. The effect size was no longer heterogeneous (P >.05) after the individual removal of 3 studies.27,32,35”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [27]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [32]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [35]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingown data

    For lifetime marijuana use, the meta-analysis found comparable odds between children with and without a history of stimulant medication treatment (OR, 1.01; 95% CI, 0.68-1.50; P=.95), with no significant heterogeneity.

    “The random-effects model estimated that children with a history of stimulant medication treatment were comparable to those without (OR, 1.01; 95% CI, 0.68−1.50; P =.95). No significant heterogeneity was observed (Q = 1.85, P =.60).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Reanalysis excluding unpublished studies was largely consistent with the main analyses, and all confidence intervals included 1.

    “Results were largely consistent with the above analyses, and in all cases the 95% CI included 1.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For lifetime nonspecific drug use, the meta-analysis found similar likelihood between medicated and nonmedicated children (OR, 1.27; 95% CI, 0.88-1.82; P=.52), with no significant heterogeneity.

    “The random-effects model for all studies estimated that children with ADHD who received stimulant medication were similar to children who did not receive stimulant medication in the likelihood of ever having used a nonspecific drug (OR, 1.27; 95% CI, 0.88−1.82; P =.52). No significant heterogeneity was detected across the 3 studies (Q = 0.39, P =.82).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    No significant publication bias was found for all substance outcomes other than marijuana use.

    “No significant publication bias was found for all other substance outcomes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The sex effect for nonspecific drug abuse or dependence appeared to be driven by the Wilens et al study; after removing that study, sex was no longer associated with effect size (t=-0.02, P=.99).

    “Notably, the same study36 removed during the sensitivity analysis appeared to be driving this sex effect.”
    • Also stated in: § MODERATORS · plain
      “When we reanalyzed the percentage of male participants without the study by Wilens et al,36 sex was no longer associated with effect size (t =−0.02, P =.99).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wilens et al,36

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingown data

    For nicotine dependence, the meta-analysis found comparable outcomes between medicated and nonmedicated children (OR, 1.34; 95% CI, 0.90-1.99; P=.15), with no significant heterogeneity.

    “The overall random-effects model estimated that children who received stimulant medication were comparable to children who did not receive medication treatment in developing later nicotine dependence (OR, 1.34; 95% CI, 0.90−1.99; P =.15). No significant heterogeneity was observed (Q = 7.87, P =.16).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The Egger test for marijuana use showed a modest association (t=-4.00, P=.06), because the largest study reported a relatively larger effect than the other three studies.

    “The bias statistic from the Egger test for marijuana use had a modest association (t = −4.00, P =.06) because the largest study reported a relatively larger effect (stimulant medication treatment was associated with higher rates of ever having used marijuana) than the 3 other studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For cocaine use, the meta-analysis estimated possibly higher odds in children treated with stimulant medication, but the confidence interval included 1 and precision was limited (OR, 2.21; 95% CI, 0.87-5.65; P=.10), with no significant heterogeneity.

    “The random-effects model estimated that children treated with stimulant medication may have higher odds of having used cocaine compared with those who did not receive stimulant medication, but the precision of the estimate is limited, and the 95% CI included 1 (OR, 2.21; 95% CI, 0.87−5.65; P =.10). No significant heterogeneity was observed (Q = 3.27, P=.20).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    For nonspecific drug abuse or dependence, leave-one-out pooled odds ratios ranged from 0.76 to 1.01, all confidence intervals included 1, and heterogeneity resolved after removing one study.

    “Sensitivity analysis for nonspecific drug abuse or dependence found pooled OR estimates ranged from 0.76 to 1.01, and all 95% CIs included 1. The effect sizes were no longer heterogeneous (P >.05) after the removal of one study.36”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationown data

    Treatment of ADHD with stimulant medication neither protects against nor increases the risk of later substance use disorders.

    “These results provide an important update and suggest that treatment of attention-deficit/hyperactivity disorder with stimulant cation neither protects nor increases the risk of later substance use disorders.”
    • Also stated in: § DISCUSSION · plain
      “The present findings do not support the sensitization hypothesis7,34 as an additional factor in the decision-making process in the treatment of ADHD, although, importantly, the present findings do not support the role of a protective effect for medication treatment for ADHD in both substance use initiation or substance use disorders across a number of substance types.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    If the medicated group had forgone medication and developed substance use problems at a higher rate, the present findings may represent a protective effect.

    “Given that medication treatment may be biased toward more severe cases,45 the present findings may indeed represent a protective effect if the group treated with stimulant medication had forgone that medication and developed substance use problems at a higher rate.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [45]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationown data

    As the proportion of children with ADHD who received stimulant medication increased, the odds ratio for alcohol abuse or dependence decreased; studies with a smaller treated proportion were more likely to have youth meet criteria for alcohol abuse or dependence.

    “As the proportion of those with ADHD who received stimulant medication increased, the OR decreased significantly. In other words, studies with a smaller proportion of individuals treated with stimulant medication were more likely to have those youth meet diagnostic criteria for alcohol abuse or dependence.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The current meta-analysis, based on a larger sample including unpublished studies, suggests no increased or reduced risk of stimulant treatment on later alcohol and substance outcomes, and this pattern was robust across substance types.

    “Crucially, findings from the current meta-analysis, based on a larger sample of studies (including several unpublished studies), suggest no increased or reduced risk of treatment with stimulant medication on later alcohol and substance outcomes and that this pattern was robust to all substance types.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Several investigators did not respond to or declined requests for unpublished data.

    “Although these efforts resulted in the addition of several studies with unpublished data, several investigators did not respond to or declined these requests.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The inference that stimulant medication treatment is unrelated to later substance outcomes is based on correlational data; without random assignment, observed group differences may reflect unmeasured confounds.

    “Second, the inference that stimulant medication treatment is unrelated to later substance outcomes is based on correlational data. That is, in the absence of random assignment to different treatment groups (eg, with and without stimulant medication), observed group differences may reflect unmeasured confounds.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductcitation

    Comorbidity in ADHD is likely salient, but few included studies compared whether substance use outcomes by medication status differed by comorbidity status or type.

    “Fourth, the issue of comorbidity in ADHD is likely to be salient15 Several studies included in the meta-analysis characterized comorbidity among ADHD probands, but few compared whether substance use outcomes based on stimulant medication status differed by comorbidity status or type.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Study design and conductown data

    The meta-analysis was unable to thoroughly assess age of medication onset, type of medication, dosages, discontinuation, adherence, and current treatment status.

    “We were unable to thoroughly assess the potential role of age of medication use onset, along with other important and relevant medication-related information thoroughly (type of medication, dosages, medication discontinuation, and treatment adherence) and, importantly, current treatment status.”
    Quote in the paperSubstantial claim
25 of 25

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In the meta-analysis of 15 longitudinal studies by Humphreys et al. (2013), studies on ADHD-children with and without stimulant medication showed inconsistent outcomes but overall similar risk of developing SUD later in life.

    “However, in the meta-analysis of 15 longitudinal studies by Humphreys et al. (2013), the studies on ADHD-children with and without stimulant medication showed inconsistent outcomes with positive, neutral, and negative outcomes, but overall, they had a similar risk of developing SUD later in life [55].”

    From Treatment of Adolescents with Concurrent Substance Use Disorder and Attention-Deficit/Hyperactivity Disorder: A Systematic Review (2021) · cites this paper as [55]

    The Discussion reports a meta-analysis of 15 longitudinal studies, mixed findings across studies, and overall comparable later substance outcomes for stimulant-treated and untreated children with ADHD. However, Study Selection notes that one included study followed children with a reading disorder rather than ADHD, so the description of all 15 studies as studies of children with ADHD is not fully accurate. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The Multimodal Treatment Study follow-up and a meta-analysis found no link between medication and substance use or problems.

    “For example, follow-up data from the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder and a meta-analysis showed no medication associations with substance use or problems (16, 17).”

    From ADHD Medication and Substance-Related Problems (2017) · cites this paper as [16]

  • Observational study conclusions are limited by possible confounding from differences between pharmacologically treated and untreated patients, known as confounding by indication.

    “At the same time, conclusions from observational studies have been constrained by the possibility of confounding from differences between patients who are and are not treated pharmacologically (i.e., confounding by indication) (16).”

    From ADHD Medication and Substance-Related Problems (2017) · cites this paper as [16]

  • A meta-analysis found that stimulants did not increase risk for nicotine abuse or dependence.

    “A meta-analysis found that stimulants did not increase the risk for alcohol (11 studies, over 1,300 participants, nicotine (6 studies, 884 participants), cocaine (7 studies, 950 participants), or cannabis abuse or dependence (9 studies, over 1,100 participants) (Humphreys et al., 2013).”

    From The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder (2021) · cites this paper as Humphreys et al., 2013

  • A meta-analysis found that stimulants did not increase risk for cannabis abuse or dependence.

    “A meta-analysis found that stimulants did not increase the risk for alcohol (11 studies, over 1,300 participants, nicotine (6 studies, 884 participants), cocaine (7 studies, 950 participants), or cannabis abuse or dependence (9 studies, over 1,100 participants) (Humphreys et al., 2013).”

    From The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder (2021) · cites this paper as Humphreys et al., 2013

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • The overall nicotine-use Q statistic has two values

    Minor

    The nicotine-use results report Q = 10.72, but the sensitivity analysis calls Q = 1.55 the overall meta-analysis estimate. The latter appears to confuse the reported odds ratio, 1.55, with Q.

  • Follow-up moderator direction conflicts with its negative t statistic

    Minor

    The paper says that longer follow-up was associated with larger odds ratios, but reports a negative t statistic for that moderator. For the stated direction of the association, the statistic should have the opposite sign.

2 of 2

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Authors
Humphreys, K. L., Eng, T., & Lee, S. S.
Affiliations
University of California, Los Angeles (US)
Corresponding author
  • Humphreys, Kathryn L.
  • Lee, Steve S.
ORCID
Humphreys, Kathryn L.
Venue
JAMA Psychiatry
Publisher
American Medical Association (AMA)
Published
2013-07-01
Volume
70
Issue
7
Pages
740
ISSN
2168-622X (ISSN-L)
DOI
10.1001/jamapsychiatry.2013.1273
PMC
PMC6688478
OpenAlex
W2151244707
Cited by
211
References
45
Citations by year
2026: 6 · 2025: 8 · 2024: 8 · 2023: 13 · 2022: 13 · 2021: 14 · 2020: 21 · 2019: 15 · 2018: 10 · 2017: 24 · 2016: 14 · 2015: 25 · 2014: 25 · 2013: 14 · 2012: 1
FWCI
14.43
Type
journal article
Language
en
Open access
Locations
  • JAMA Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (submittedVersion)
  • PubMed Central (submittedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
stimulant medication, attention deficit hyperactivity disorder, substance use disorders, substance abuse, substance dependence, alcohol consumption, cocaine use, cannabis use
MeSH terms
Adolescent, Adult, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, Female, Humans

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