Stimulant treatment for attention-deficit hyperactivity disorder and risk of developing substance use disorder

Groenman, Annabeth P.; Oosterlaan, Jaap; Rommelse, Nanda; Franke, Barbara; Greven, Corina U.; Hoekstra, Pieter J.; Hartman, Catharina A.; Luman, Marjolein; Roeyers, Herbert; Oades, Robert D.; Sergeant, Joseph A.; Buitelaar, Jan K.; Faraone, Stephen V.

doi:10.1192/bjp.bp.112.124784

Cited by 70 publications

(43 citation statements)

References 35 publications

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“…Interestingly, our results suggest that insensitivity to a drug that is used to treat ADHD might be a genetic risk factor for ADHD; however, it is important to note that we examined sensitivity to the euphoric effects of amphetamine and not sensitivity to its therapeutic effects. Our results are consistent with studies that have shown a protective effect from substance use disorders in stimulant-treated adolescents with ADHD (22,23).…”

Section: Discussionsupporting

confidence: 93%

Genetic variation associated with euphorigenic effects of d -amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder

Hart

Gamazon²,

Engelhardt

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Here, we extended our findings from a genome-wide association study of the euphoric response to d-amphetamine in healthy human volunteers by identifying enrichment between SNPs associated with response to d-amphetamine and SNPs associated with psychiatric disorders. We found that SNPs nominally associated (P ≤ 0.05 and P ≤ 0.01) with schizophrenia and attention deficit hyperactivity disorder were also nominally associated with d-amphetamine response. Furthermore, we found that the source of this enrichment was an excess of alleles that increased sensitivity to the euphoric effects of d-amphetamine and decreased susceptibility to schizophrenia and attention deficit hyperactivity disorder. In contrast, three negative control phenotypes (height, inflammatory bowel disease, and Parkinson disease) did not show this enrichment. Taken together, our results suggest that alleles identified using an acute challenge with a dopaminergic drug in healthy individuals can be used to identify alleles that confer risk for psychiatric disorders commonly treated with dopaminergic agonists and antagonists. More importantly, our results show the use of the enrichment approach as an alternative to stringent standards for genome-wide significance and suggest a relatively novel approach to the analysis of small cohorts in which intermediate phenotypes have been measured.G enome-wide association studies (GWAS) implicitly assume that all SNPs in the genome are equally likely to be causal, although most SNPs are unlikely to have any functional consequences. Studies from our groups and others have shown the use of incorporating prior information about SNPs into the genetic analysis of complex traits, including autism and bipolar disorder (1-6). These studies have shown that there is an enrichment of SNPs with functional consequences (e.g., expression quantitative trait loci) among SNPs modestly associated with a broad spectrum of complex traits.We recently conducted, to our knowledge, the first GWAS of an intermediate pharmacogenetic phenotype, namely the acute subjective response to a drug of abuse, d-amphetamine, in a sample of 381 healthy human volunteers (7). We identified only one genomewide significant association, and no replication samples were available; thus, the results were difficult to interpret. In the present study, we sought to further interrogate the numerous nominally significant associations from our d-amphetamine response GWAS. We hypothesized that nominally significant associations would be mostly false positives but also, would be enriched for true positives.Amphetamine produces its subjective and behavioral effects in part by increasing synaptic levels of dopamine (8). We took advantage of prior GWASs for psychiatric disorders to identify a subset of SNPs that showed nominal association with both amphetamine response and psychiatric disorders in which dopaminergic signaling is also hypothesized to play an important role. We predicted that, if these different phenotypes had shared susceptibility alleles, then we would ...

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Section: Discussionsupporting

confidence: 93%

Genetic variation associated with euphorigenic effects of d -amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder

Hart

Gamazon²,

Engelhardt

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…This is more alarming, since adolescence is a vulnerable period of development with complex changes of the youngsters' social, educational and occupational environment and increased risk for emergence of new psychiatric disorders and comorbidities. Data indicate that continued medication use during adolescence improves academic outcomes and postpones substance initiation (Barbaresi et al 2007;Wilens et al 2008;Biederman et al 2009;Groenman et al 2013). A factor with great bearing on the discontinuity of care is that mental health services for children and adolescents in most countries are provided till age 18, and in some exceptions till age 21.…”

Section: First Published Online 17 April 2017mentioning

confidence: 99%

Optimising treatment strategies for ADHD in adolescence to minimise ‘lost in transition’ to adulthood

Buitelaar

2017

Epidemiol Psychiatr Sci

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The persistence of attention-deficit hyperactivity disorder (ADHD) from adolescence to adulthood is not matched by continuity of care in this transition period. Many adolescents with ADHD have poor medication adherence or even stop medication treatment, and use of behavioural interventions is also suboptimal. The present commentary focuses on treatment strategies that might improve effects of ADHD medication treatment by improving adherence in adolescents with ADHD and/or optimise behavioural interventions for ADHD in adolescence. Most treatment strategies in adolescents with ADHD are merely copied from treatments offered to children. Instead however treatment should be focused on what makes adolescents special and vulnerable, such as poor insight into own functioning and poor decision making. Techniques that offer promise for adolescents are motivational interviewing, use of ecological momentary assessments and interventions, mindfulness-based training and serious games. Systematic studies into the effects of these techniques alone and in combination with medication are lacking. First published online 17 April 2017Key words: Attention-deficit hyperactivity disorder, transition, adolescence, mental health services.Attention-deficit hyperactivity disorder (ADHD) is a rather common neurodevelopmental disorder with an estimated prevalence of at least 5% in children and adolescents and 2.5% in adults (Polanczyk et al. 2007;Simon et al. 2009). Onset of the disorder is mostly during the preschool years or in childhood. From the three defining symptoms of ADHD, inattentiveness tends to be rather stable over development, whereas hyperactivity and impulsivity tend to decline more over age (Biederman et al. 2000). Despite these age-related symptomatic improvements, ADHD is a highly persistent disorder with between one third and half of ADHD children still meeting clinical threshold criteria and the majority of children with ADHD being functional impaired at adult age (Faraone et al. 2015).Despite claims of overdiagnosis and overtreatment of ADHD, survey data about treatments received for ADHD among children with special needs tell a different story (Visser et al. 2015). Of all adolescents of a national representative USA sample of 12-17 year old with ADHD, 27.9% were reported to have received both medication and behavioural interventions in the last year, 48.3% received medication only, 12.5% received behavioural interventions only and 14.3% did receive neither medication nor behavioural interventions (Visser et al. 2015). Furthermore, the persistence of the disorder over adolescence into adulthood is not matched by continuity of care in this important phase of life. For example, prescription data of ADHD medication by UK general practitioners show a significant drop from age 15 to 21 years. This discontinuation of medication treatment is much greater than the agerelated decline in symptoms, suggesting that young adults with ADHD receive insufficient treatment (McCarthy et al. 2009). This is more alarming, since adolescen...

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“…Wilens et al suggested that on the contrary, the use of stimulants in childhood might actually decrease the risk of future drug and alcohol use disorders [16,17]. Other, more recent studies have continued to show that stimulants might have a protective effect in mitigating the risk for later substance abuse [18]. However, the evidence on whether stimulants decrease the risk for later substance abuse is inconsistent.…”

Section: Substance Abusementioning

confidence: 99%

Long-Term Effects of Stimulant Treatment for ADHD: What Can We Tell Our Patients?

Craig

Davies²,

Schibuk³

et al. 2015

Curr Dev Disord Rep

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Introduction Stimulant medication is a well-researched treatment for attention deficit hyperactivity disorder (ADHD) and is among the most effective treatments in psychiatry. Parents often want to know more about the long-term risks and benefits of medication. Our objective was to review the seminal papers on long-term outcomes of stimulant treatment for ADHD for the purpose of providing clinicians with the background they need to interpret these findings for patients. Methods We reviewed key articles on long-term outcome of symptoms, comorbidity, substance use, executive functioning, academics, side effects, neurobiology, functioning, and quality of life. Results Stimulants are very effective medications in the short term when used optimally. Long-term randomized, placebocontrolled studies are not feasible. Long-term naturalistic studies are limited by absence of controls.Discussion When administered properly with careful titration, follow-up, and dose adjustment, stimulants are a safe and effective treatment for ADHD with minimal long-term risk and possible long-term benefit.

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Stimulant treatment for attention-deficit hyperactivity disorder and risk of developing substance use disorder

Abstract: Stimulant treatment appears to lower the risk of developing substance use disorders and does not have an impact on the development of nicotine dependence in adolescents with ADHD.

Cited by 70 publications

References 35 publications

Genetic variation associated with euphorigenic effects of d -amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder

Genetic variation associated with euphorigenic effects of d -amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder

Optimising treatment strategies for ADHD in adolescence to minimise ‘lost in transition’ to adulthood

Long-Term Effects of Stimulant Treatment for ADHD: What Can We Tell Our Patients?

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