Stimulant Therapy and Risk for Subsequent Substance Use Disorders in Male Adults With ADHD: A Naturalistic Controlled 10-Year Follow-Up Study

Research Program in Pediatric Psychopharmacology and Adult ADHD, Department of Psychiatry, Massachusetts General Hospital, Boston 02114, USA. biederman@
American Journal of Psychiatry (Impact Factor: 12.3). 06/2008; 165(5):597-603. DOI: 10.1176/appi.ajp.2007.07091486
Source: PubMed


The extant literature does not provide definite answers pertaining to whether stimulant treatment increases, decreases, or does not affect the risk for subsequent substance use disorders in youths with attention deficit hyperactivity disorder (ADHD). The authors examined the association between stimulant treatment in childhood and adolescence and subsequent substance use disorders (alcohol, drug, and nicotine) into the young adult years.
The authors conducted a 10-year prospective follow-up study. One hundred forty male Caucasian children with ADHD, ages 6 to 17, were examined at baseline. Of these, 112 (80%) were reassessed at the 10-year follow-up (mean age at follow-up=22 years). Assessments were made using Cox proportional hazards survival models. All models were adjusted for conduct disorder, since conduct disorder is a potent predictor of subsequent substance use disorders.
Of the 112 ADHD subjects who were reassessed at the 10-year follow-up, 82 (73%) had been treated previously with stimulants and 25 (22%) were undergoing stimulant treatment at the time of the follow-up assessment. There were no statistically significant associations between stimulant treatment and alcohol, drug, or nicotine use disorders.
The findings revealed no evidence that stimulant treatment increases or decreases the risk for subsequent substance use disorders in children and adolescents with ADHD when they reach young adulthood.

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Available from: Michael C Monuteaux, Oct 29, 2014
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    • "Confirmation of the genetic vulnerability to SUD offers the possibility of early identification and targeted preventive interventions for ADHD patients at genetically increased risk for addiction. Treatment of children with ADHD with stimulant medication has shown some promise in diminishing but not eliminating the risk for later addiction (Biederman et al., 2008; Wilens et al., 2003). A better understanding of the genetic underpinnings of addiction could help us identify which patients would benefit most from ADHD medication and which patients would be better served by other interventions. "
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    ABSTRACT: The shared genetic basis of attention deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) was explored by investigating the association of candidate risk factors in neurotransmitter genes with both disorders. One hundred seven methadone maintenance treatment patients, 36 having an ADHD diagnosis, 176 adult patients with ADHD without SUDs, and 500 healthy controls were genotyped for variants in the DRD4 (exon 3 VNTR), DRD5 (upstream VNTR), HTR1B (rs6296), DBH (rs2519152), COMT (rs4680; Val158Met), and OPRM1 (rs1799971; 118A>G) genes. Association with disease was tested using logistic regression models. This pilot study was adequately powered to detect larger genetic effects (OR≥2) of risk alleles with a low frequency. Compared to controls, ADHD patients (with and without SUDs) showed significantly increased frequency of the DBH (rs2519152: OR 1.73; CI 1.15-2.59; P=0.008) and the OPRM1 risk genotypes (rs1799971: OR 1.71; CI 1.17-2.50; P=0.006). The DBH risk genotype was associated with ADHD diagnosis, with the association strongest in the pure ADHD group. The OPRM1 risk genotype increased the risk for the combined ADHD and SUD phenotype. The present study strengthens the evidence for a shared genetic basis for ADHD and addiction. The association of OPRM1 with the ADHD and SUD combination could help to explain the contradictory results of previous studies. The power limitations of the study restrict the significance of these findings: replication in larger samples is warranted.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 07/2012; 23(6). DOI:10.1016/j.euroneuro.2012.07.003 · 4.37 Impact Factor
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    • "), treatment itself does not necessarily appear to increase the likelihood of drug use in adolescence and/or adulthood. Among young adults treated as children or currently in treatment, rates of drug, alcohol, or nicotine abuse have been reported to not be significantly different from rates in a sample of healthy untreated controls (Biederman et al, 2008; Mannuzza et al, 2008). In these studies, there was some suggestion that the earlier treatment is initiated the smaller the likelihood of substance abuse in young adulthood. "
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    ABSTRACT: Despite the widespread use of stimulant medications for the treatment of attention deficit hyperactivity disorder, few studies have addressed their long-term effects on the developing brain or susceptibility to drug use in adolescence. Here, we determined the effects of chronic methylphenidate (MPH) treatment on brain dopamine (DA) systems, developmental milestones, and later vulnerability to substance abuse in juvenile nonhuman primates. Male rhesus monkeys (approximately 30 months old) were treated daily with either a sustained release formulation of MPH or placebo (N=8 per group). Doses were titrated to achieve initial drug blood serum levels within the therapeutic range in children and adjusted throughout the study to maintain target levels. Growth, including measures of crown-rump length and weight, was assessed before and after 1 year of treatment and after 3-5 months washout. In addition, positron emission tomography scans were performed to quantify binding availability of D2/D3 receptors and dopamine transporters (DATs). Distribution volume ratios were calculated to quantify binding of [(18)F]fluoroclebopride (DA D2/D3) and [(18)F]-(+)-N-(4-fluorobenzyl)-2β-propanoyl-3β-(4-chlorophenyl)tropane (DAT). Chronic MPH did not differentially alter the course of weight gain or other measures of growth, nor did it influence DAT or D2/D3 receptor availability after 1 year of treatment. However, after washout, the D2/D3 receptor availability of MPH-treated animals did not continue to decline at the same rate as control animals. Acquisition of intravenous cocaine self-administration was examined by first substituting saline for food reinforcement and then cocaine doses (0.001-0.1 mg/kg per injection) in ascending order. Each dose was available for at least five consecutive sessions. The lowest dose of cocaine that maintained response rates significantly higher than saline-contingent rates was operationally defined as acquisition of cocaine reinforcement. There were no differences in rates of acquisition, overall response rates, or cocaine intake as a function of cocaine dose between groups. In an animal model that closely mimics human development; chronic treatment with therapeutic doses of sustained release MPH did not have a significant influence on the regulation of DATs or D2/D3 receptors, or on standard measures of growth. Furthermore, this treatment regimen and subsequent drug washout did not have an impact on vulnerability to cocaine abuse.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 07/2012; 37(12):2555-65. DOI:10.1038/npp.2012.117 · 7.05 Impact Factor
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    • "There is some amount of risk of abuse with MPH-IR formulations (Findling, 2008[38]). Concerns on an increase in the risk of drug and alcohol abuse disorders later in life in ADHD children treated with stimulants have not been supported by research (Wilens et al., 2003b[134]; Biederman et al., 2008a[16]; Mannuzza et al., 2008[66]). "
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    ABSTRACT: Attention deficit hyperactivity disorder is a developmental disorder with an age onset prior to 7 years. Children with ADHD have significantly lower ability to focus and sustain attention and also score higher on impulsivity and hyperactivity. Stimulants, such as methylphenidate, have remained the mainstay of ADHD treatment for decades with evidence supporting their use. However, recent years have seen emergence of newer drugs and drug delivery systems, like osmotic release oral systems and transdermal patches, to mention a few. The use of nonstimulant drugs like atomoxetine and various other drugs, such as α-agonists, and a few antidepressants, being used in an off-label manner, have added to the pharmacotherapy of ADHD. This review discusses current trends in drug therapy of ADHD and highlights the promise pharmacogenomics may hold in the future.
    03/2012; 10(1):45-69. DOI:10.4103/0973-1229.87261
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