ADHD Subtypes and Subgroups at Risk for Substance Use Disorders
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Transcript of ADHD Subtypes and Subgroups at Risk for Substance Use Disorders
ADHD Subtypes and Subgroups at Risk ADHD Subtypes and Subgroups at Risk for Substance Use Disordersfor Substance Use Disorders
Naimah Weinberg, M.D., DiscussantMedical Officer
National Institute on Drug Abuse, NIH
What is SUD?
Substance Use Disorder (abuse or dependence), per DSM
Distinct from substance use: while use appears driven by both biological and environmental factors, progression to abuse & dependence largely influenced by individual-level (genetic, psychiatric) factors
Difficult to apply to adolescents, but no current standardized substitute
Some studies use early onset drug use as proxy for SUD
Current research questions Is ADHD a risk factor for SUD?
Which children with ADHD might be at increased risk? for which substances?
Why might some children with ADHD be at increased risk for SUD?
Does treatment of ADHD alter risk for SUD?
Does stimulant treatment alter risk for SUD?
Is ADHD a risk factor for SUD?
Many clinical studies and reports suggest it is
HOWEVER: Not population based (referral bias)
Some didn’t take comorbidity into account
Many are retrospective (subject to systematic recall bias)
Population-based studies
Population-(or community-)based studies are needed to validate clinical studies because:
Clinic samples more likely to include comorbidity
Clinic and community samples may differ in severity, comorbidity patterns, temporal ordering, risk factors, treatment history
Seeming risk factors for disorder may actually be markers of likelihood for referral (e.g. poverty and Medicaid) Armstrong & Costello, 2002
Population-based studies of ADHD and SUD
A few so far
Taken together, do not support ADHD as risk factor when CD is taken into account
Comorbidity
Is very common in children with ADHD
Often associated with worse outcomes
Numerous studies: factoring in CD -> ADHD drops out as SUD risk factor
However, some recent literature finding a contribution of ADHD in presence of CD
Externalizing-internalizing combination also associated w/increased SUD risk
Is ADHD a risk factor for SUD? II
Many clinical studies and reports suggest it is
HOWEVER: Not population based (referral bias)
Some didn’t take comorbidity into account
Many are retrospective (subject to recall bias)
So it isn’t yet clear
Which children with ADHD might be at increased risk?
Clinically derived; may offer clues to further study
Comorbid psychiatric disorders
Family history of SUD (may contribute to both ADHD and SUD)
Persistent ADHD
Social skills deficits
Which children might be at increased risk? (con’t)
Severity of childhood symptoms?
Inattention (for tobacco)?
Impulsivity or disinhibition (for other drugs)?
Gender differences: findings contradictory so far
Ethnic or racial group differences: inadequately studied so far
Why might some with ADHD be at increased risk for
SUD?Biologically: mostly common risk factors, a few
mediators
Psychosocially/environmentally: mostly mediators between ADHD and (early) substance use
And these interact
Why might some be at increased risk for SUD? (con’t)
May both be manifestations of behaviorally disinhibited phenotype
Executive cognitive dysfunction present in ADHD and predicts SUD (in high risk samples)
Temperament: novelty seeking, low constraint – may mediate, maybe affect dysregulation
Why might some be at increased risk for SUD? (con’t)
Other biological associations: Through prenatal exposure to alcohol, smoking, perhaps drugs
Low birth weight
Dopaminergic system: Self-medication? (especially tobacco)
Perhaps an internalizing/inattentive/self-medicating late-onset subtype?
Perhaps sensitization through use of stimulants
Why might some be at increased risk for SUD? (con’t)
Psychosocial factors that might impact use/early use:
Weak attachment to & conflict with parents, school secondary to behavior problems
Disordered alcohol or drug expectancies
Association with deviant peers
Attribution (fulfilling expectations)?
Parental modeling, monitoring, coping (ADHD parents or child-induced)
Does treatment of ADHD alter the risk for SUD?
Little data so far
Focus of ongoing and new studies
However, controlled clinical studies lacking
Answers could help us disentangle etiologic role of ADHD in risk for drug abuse
Does stimulant treatment alter the risk for SUD?
Prescription stimulants: Methylphenidate (Ritalin)
Amphetamines (Dexedrine, Adderall)
Pemoline (Cylert)
Prescription estimates: 3% - >6% of American schoolchildren
How they act: release and/or block reuptake of dopamine into presynaptic neuron
Does stimulant treatment alter the risk for SUD? II
Why might stimulant medication increase risk for SUD?
Psychologically: engender drug-taking attitudes, use of drug to solve problems; reliance on medication reduces efforts to develop other coping mechanisms or pursue other treatments
Biologically: sensitization, i.e. persistent hypersensitivity to drug effects as result of prior exposure (both stimulants and drugs of abuse act through increased dopamine transmission)
Does stimulant treatment alter the risk for SUD? III
Why might stimulant medication reduce risk for SUD?
Psychologically: through improved self-esteem, academic achievement, relationships, parent monitoring
Biologically: reduce “self-medication”; may alter reinforcing properties of drugs; hypothesized that early stimulant treatment normalizes white matter volume, in turn enhancing executive function and reducing later SUD risk
Does stimulant treatment alter the risk for SUD? IV
Human follow up studies: findings Most show no effect or a protective effect Meta-analysis of 5 studies -> 2.3-fold reduced risk for SUD
associated with stimulant treatment in youth (Wilens et al, 2003)
However, some have found increased rates of SUD outcomes
“Protection” may depend on age at prescription, and may dissipate by adulthood
Does stimulant treatment alter the risk for SUD? V
Human follow up studies: weaknesses
NOT RANDOMIZED! Self-selection effects and biases: which children receive
medication may be function of factors that alter risk
Possible cohort effects on prescription patterns
Need to take into account age at prescription, age at assessment, length of follow up
Does stimulant treatment alter the risk for SUD? VI
Animal studies: findings Recent refinements studying pre- and peri-adolescent rats, using
therapeutic-range dosages of methylphenidate Show long-lasting behavioral and neurobiological adaptations, and
altered responses to reinforcing properties of cocaine in adulthood Results inconsistent: some show enhanced reinforcement by
cocaine, some reduced Response appears to be sensitive to age at administration: younger
reduces reinforcement
Does stimulant treatment alter the risk for SUD? VII
Animal studies: weaknesses Rats don’t have ADHD
Rats lack human prefrontal cortex
Medication not administered orally
Outcome measures open to interpretation
Volkow & Insel, 2003; Hyman, 2003
Does stimulant treatment alter the risk for SUD? VIII
Perhaps no single answer: impact on risk may depend on subtype, interaction with other risk and protective factors, age at medication administration, medication response, choice of stimulant
Or, no impact
Summary of the science
Lack population-based data supporting ADHD itself as a risk factor for drug abuse
Subgroups appear to be at increased risk: comorbid disorders esp. conduct, family history of drug abuse, perhaps more severe or impairing ADHD
Understanding impact of pharmacologic and behavioral treatments is important, controversial, and not yet clear
Sources of divergence
Methodologic: measures, samples (self-selection), constructs, covariates, timing, length of follow up
Individual factors: stimulant exposure, family history, comorbidity
State of research
Several NIDA-funded studies underway (many population-based) to address these questions
Data from studies funded by NIMH, NICHD, NIAAA might also be mined to address
For clinical (treatment) questions, data from controlled clinical trials are lacking; MTA may be opportunity
Public health implications
Major public health issues, given prevalence of ADHD, SUD, stimulant use, individual and social costs of these disorders
More work needed on all these questions
Ultimate goal: reduction and prevention of SUD and associated adverse outcomes
Public health implications II
For etiologic questions: require sophisticated transdisciplinary approaches, that nest imaging, neurocognitive tests, behavioral pharmacology, genetics research in studies of population-based samples
For treatment issues: need randomized studies (within ethical limits; MTA), prospective studies, creative methodologic approaches, developmental sensitivity, and to take family history of SUD into account
Etiologic and prevention research can and must be used to inform each other