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ADHD and Addiction: Diagnosis and Management
 

ADHD and Addiction: Diagnosis and Management

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Presentation by Jacob Kagan MD on the diagnosis and management of ADHD and Substance Abuse Disorders, including epidemiology and comorbid conditions,...

Presentation by Jacob Kagan MD on the diagnosis and management of ADHD and Substance Abuse Disorders, including epidemiology and comorbid conditions,
causality and functional impact, potential explanations for the ADHD/SUD association,stimulant treatment and the risk for SUDs, diversion and misuse of stimulant medications, and treatment recommendations. http://jacobkaganmd.com

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    ADHD and Addiction: Diagnosis and Management ADHD and Addiction: Diagnosis and Management Presentation Transcript

    • ADHD and Addiction: Diagnosis and Management Jake Kagan, MD Outpatient Addiction Services Cambridge Health Alliance
    • Outline
      • ADHD diagnosis and complications of diagnosis
      • ADHD epidemiology and comorbid conditions
      • ADHD and substance use disorder (SUD) epidemiology
      • Association between ADHD and SUDs: determining causality and functional impact
      • Potential explanations for the ADHD/SUD association
      • Stimulant treatment and the risk for SUDs
      • Diversion and misuse of stimulant medications
      • Treatment recommendations
    • Making the ADHD diagnosis: DSM criteria
    • Inattention symptoms
      • Six (or more) of the following symptoms of inattention have persisted for at least 6 months …
        • fails to give close attention to details or makes careless mistakes
        • difficulty sustaining attention
        • does not seem to listen when spoken to directly
        • does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace
        • has difficulty organizing tasks and activities
        • avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (such as schoolwork or homework)
        • loses things necessary for tasks or activities
        • often easily distracted by extraneous stimuli
        • often forgetful in daily activities
    • Hyperactivity/Impulsivity Symptoms
      • Six (or more) of the following symptoms of hyperactivity/impulsivity have persisted for at least 6 months …
      • Hyperactivity
        • fidgets or squirms in seat
        • leaves seat
        • Often runs about or climbs excessively (in adolescents or adults, may be limited to subjective feelings of restlessness)
        • has difficulty playing or engaging in leisure activities quietly
        • "on the go" or often acts as if "driven by a motor"
        • talks excessively
      • Impulsivity
        • blurts out answers before questions have been completed
        • has difficulty awaiting turn
        • interrupts or intrudes on others
    • DSM-IV Diagnosis
      • Symptoms that caused impairment were present before age 7 years.
      • Evidence of clinically significant impairment in social, academic, or occupational functioning.
      • Impairment present in two or more settings (e.g., at school [or work] and at home).
      • The symptoms do not occur exclusively during the course of a Pervasive Developmental Disorder, Schizophrenia, or other Psychotic Disorder and are not better accounted for by another mental disorder (e.g., Mood Disorder, Anxiety Disorder, Dissociative Disorder, or a Personality Disorder).
      • Subtypes – Primarily Inattentive (6), Hyperactive/Impulsive (6), or Combined Type (6+6)
    • Making the ADHD diagnosis (general points)
      • ADHD is a disorder of both childhood and adulthood
      • ADHD is highly comorbid with substance use disorders
      • Follow the general rule of evaluating sxs during periods of sobriety
      • Collateral hx can be crucial as the sxs should have been present prior to age 7
      • The diagnosis is a CLINICAL one – ie. neuropsych can be a helpful adjunct but is insufficient alone to make the dx.
      • ADHD may be better described as a dimensional rather than categorical diagnosis
    • Making the ADHD diagnosis (clinical reality!)
      • Sxs in adults can present differently 1
      • Hyperactive sxs may “resolve”, or may be adapted to with life changes
      • Impulsivity can present functionally (ending relationships, quitting jobs, arrests, driving violations) – and may be better elicited as such
      • Adult ADHD may actually be better dx’d with either different or perhaps less stringent criteria
      • Adults frequently can not recall sxs prior to age 7 – particularly in chaotic households!
      • Again, collateral data wherever possible, including report cards/testing results
      • Concept of “late-onset” ADHD challenges stringent age criteria, as research shows this population to be similar to “full” ADHD 2
      • Comorbidities may complicate diagnosis…
        • Depression:
          • attention/concentration are shared sxs
          • chronic suggests ADHD, guilt/worthlessness, suicidality all suggest depression
        • Bipolar Disorder:
          • hyperactivity, inattention, talkativeness, impulsivity are shared
          • Grandiosity, expansive mood and a cyclical pattern vs chronicity suggest Bipolar Disorder
        • Pay attention to family history
      Making the ADHD diagnosis (clinical reality!)
    • Epidemiology of ADHD
      • Attention-Deficit Hyperactivity Disorder (ADHD) prevalence is approx. 3-7% in school age children 3
      • 75% of children continue to have sxs into adolescence, approximately 50% into adulthood 4
      • Adult prevalence is estimated to be 3-5% 5
      • ADHD is over-represented in substance abusing populations and SUDs similarly in adults with ADHD
    • Epidemiology of ADHD (continued)
      • There are also high rates of other Axis I disorders among adult ADHD populations (NCS-R) 5
      • 38% 12-month prevalence for any mood disorder
      • 19% for MDD, 19% for Bipolar Disorder
      • 47% 12-month prevalence for any anxiety disorder
      • Conduct disorder is also highly comorbid with ADHD – reportedly 30-50% in adolescents 6
    • ADHD and SUD comorbidity
      • NCS-R data 5 :
        • Among adults with ADHD, 12-month prevalence for any SUD is 15% vs 5% in non-ADHD responders
        • Among those w/SUDs, ADHD prevalence is 11% vs 4%
      • In clinical samples, percentages are higher! 7
        • 17-45% ADHD adults have h/o EtOH abuse or dependence
        • 9-30% ADHD adults have h/o drug abuse/dependence
      • Opioid dependent pts: 5-22% with ADHD 8
      • Cocaine dependent pts: 10-35% 8
      • EtOH dependent pts: 33-71% 8
    • Potential impact of ADHD on SUDs
      • Given the bidirectional preponderance, early work reported associations, but also assumed causality.
      • Early work reported that individuals with co-occurring ADHD had:
        • Earlier onset of substance use
        • More severe course of SUD
        • Poorer treatment adherence
        • More difficulty achieving treatment goals
      • Examples: Carroll & Rounsaville (cocaine) 9 , Wise et al. (adolescents seeking residential treatment) 10
      • Criticisms:
        • Retrospective studies prone to possible recall bias
        • Often failed to account for comorbidies – ie Conduct Disoder!
        • Fail to look at individual drugs, gender and dimensional ADHD sxs or subtypes
    • Rethinking old data, and new research
      • The role of conduct d/o
      • ADHD symptom dimensions vs categorical diagnosis
      • Specific substances of abuse/dependence
    • Conduct Disorder: A complicating factor?
      • Given that Conduct Disorder is so highly comorbid with ADHD and also with SUDs, could this account for the association?
      • Flory and Lynam’s 2003 review suggests that ADHD alone (controlling for Conduct D/O) is not associated with a significant risk for SUDs, although ADHD + CD may afford higher risk then either alone 11
      • 2 subsequent prospective studies support this trend:
        • August et al. (2006) 12 – ADHD+CD group at higher risk for SUD, but risk disappears when CD controlled for
        • Barkley et al. (2004) 13 – also ADHD+CD with increased risk, and not ADHD alone, although ADHD severity independently linked to “drug related antisocial activity”
      • To the contrary…
      • Even within the body of data reviewed by Flory and Lynam 11 , multiple studies show that ADHD predicts earlier tobacco use and dependence, independent of CD
      • More recent studies:
        • Molina & Pelham (2003) 14 prospectively study 142 subjects:
          • Inattentive sxs predict ealier use of drugs, frequency of EtOH/MJ use and heavier tobacco use even controlling for CD.
          • CD+ADHD = more use and problems.
      Conduct Disorder: A complicating factor? (continued)
    • Conduct Disorder: A complicating factor? (continued)
      • More recent studies (cont):
      • Elkins et al. (2007) 15 use Minnesota twin data to examine dimensional aspects of ADHD/CD (760F, 752M)
        • Initiation of use: Hyperactive/imp sxs significantly predict use of tobacco/EtOH/illicit drugs, as does CD, inattentive sxs only EtOH and ADHD dx tobacco/illicit drugs only
        • SUDs: HI sxs predict tobacco/MJ, inattentive predict no SUDs, CD predict tobacco/MJ/EtOH, ADHD dx predicts none
        • Hyperactive/impulsive sxs emerge as important
      • Arias et al. (2008) – retrospective analysis of 2047 individuals ascertained in siblings pairs from community sample (although only 92 pts dx’d with ADHD)
        • ADHD associated with earlier age of substance use, more SUD dxs, more psych dxs, more suicide attempts/hospitalizations
        • ADHD/SUD pts may represent a more severe phenotype of addicted patients
    • What to make of all this?!?
      • Conduct D/O independently and significantly predicts risk of SUDs
      • ADHD may independently predict SUDs, in particular nicotine use/dependence
      • Investigation of IN/HI sxs subsets is clearly important, and recent data suggests hyperactivity/impulsivity as significant risks for SUDs
      • ADHD in combination with CD likely predicts a risk of SUDs/outcomes greater than ADHD or CD alone
    • Why the relationship between SUD and ADHD?
      • Self medication?
        • Anecdotal theories: pts use nicotine/MJ/cocaine to increase focus/attention, EtOH/MJ/opioids to calm internal sense of restlessness, or that impulsivity predisposes to use
        • Some supporting data: Wilens et al. (2007) 16 find on self-report scales that 36% of ADHD pts cited “self-medication” as a motivation to use vs. 25% to “get high”
      • Familial link?
        • Recent work by Biederman et al. (2008) 17 suggests a variable expressivity model for ADHD and drug dependence (shared risk factors), but independent transmission for EtOH dependence
        • This work suggests shared risks but does not necessarily imply genetic links – ie environment can not be ruled out
    • ADHD and Substance Abuse: Potential biological pathways
      • Dopamine (DA) pathways:
      • ADHD is almost certainly a polygenic disorder (multiple different genes interacting with environmental stressors)
      • Genes implicated include DA transporter and receptor genes, enzymes involved in metabolism, although also serotonin receptor/transporter genes
      • However, DA is particularly interesting given the DA dysfxn associated with addictive disorders
      • Specifically, DA dysfunction in prefrontal regions, subcortical structures (dorsal/ventral striatum) and connecting circuits may provide a common pathway between ADHD and addictive disorders
    • ADHD and Substance Abuse: Potential biological pathways
      • Preliminary research:
      • Adults with ADHD have been found to have decreased DA synthesis/metabolism in prefrontal cortex 18 in addition to decreased DA release in the caudate and decreased DA receptor availability (D2/D3) 19
      • Decreased DA release in caudate correlates with inattentive sxs AND “drug liking” responses to IV methylphenidate (Ritalin) 19
      • Decreased DA in these regions (or decreased receptor availability) may modulate reinforcing effect of substances of abuse
      • Both alcohol and cocaine dependence are associated with decreased dopamine receptor availability (D2/D3) and decreased DA release in the ventral striatum (NAc) and putamen 21,22
    • Relationship between stimulant treatment and SUDs
      • Does stimulant tx decrease, increase or have no effect on the risk of developing a SUD?
      • Concern stems from “sensitization hypothesis” – that early exposure to stimulants alters DA system, increasing reinforcing effects of substances
      • In some rat models, adolescent animals exposed to methylphidate are more likely to self administer cocaine as adults 22
      • However, even in rat models, data is at times contradictory!
        • Route of administration is likely important (IM vs oral)
        • Length of exposure also likely important, as is age of exposure
        • Dose/pharmacokinetics are hard to match up with humans
        • Thanos et al. (2007) find that 2 mo oral treatment in adolescent rats lead to increased cocaine self-administration, while 8 mo of treatment actually decreased cocaine SA 23
      Relationship between stimulant treatment and SUDs
    • Relationship between stimulant treatment and SUDs
      • Studies in humans…
      • Through 80s and 90s conflicting data emerged, showing increased risk/no risk/decreased risk of SUD associated with prior stimulant tx
      • 2003: Wilens et al. perform meta-analysis revealing small protective effect of stimulant tx on later SUDs 24
        • Only 6 studies included
        • Protective effect much greater on adolescent use than adult use…
      • Why?
      • Adolescents more closely monitored by parents?
      • Adolescents hadn’t passed through “full risk period”?
    • Relationship between stimulant treatment and SUDs
      • More recent studies…
      • Faraone et al. (2007) 25 – retrospective data in adults with ADHD (n=206), separated by exposure to stimulant tx
        • No differences in prevalence of nicotine/EtOH/drug use/abuse/dep
        • Also no protective effect
      • Biederman et al. (2008) 26 – 10 year f/u data from prospective study of boys with ADHD
        • At f/u subjects were in early 20s
        • No evidence of increased SUDs but also no protective effect
        • 4 year f/u data actually showed protective effect, again suggesting that stimulant tx may delay onset of substance use
    • Relationship between stimulant treatment and SUDs
      • More recent studies…
      • Wilens et al. (2008) 27 – 5 year f/u data from prospective study of girls with ADHD (mean age 16)
        • Stimulant tx associated with decreased risk of SUDs
      • Mannuzza et al (2008) 28 – f/u data of boys ascertained in 1970s, evaluated in late adolescence and adulthood (20s)
        • Risk of SUD was associated with age of stimulant tx – ie kids treated later had a significantly higher risk
        • Development of antisocial personality disorder largely accounted for the increased risk – ie kids who were treated were less likely to develop ASPD and then SUDs
      • Conclusions: At this time there is no convincing evidence that stimulant treatment increases the risk for SUDs, but also no conclusive evidence of a decreased risk.
    • Concerns about diversion/misuse of stimulants
      • Among middle school and HS students, 23% of those prescribed stimulants were asked for their meds, 4.5% of total sample reported misuse/diversion 29
      • Among college students lifetime prevalence of stimulant misuse between 6-16% 30, 31, 32
      • More likely to be white, male, fraternities/sororities and lower grades
      • In Biederman’s 10-year prospective study of boys with ADHD, 22% admitted misusing their medications, 11% diverting 33
      • All of misuse attributed to conduct disorders or substance use disorders and occurred with immediate release meds
      • Little clinical data available about risks in pts with SUDs and ADHD
    • Treatment Recommendations
      • Careful thoughtful diagnosis with collateral data
      • Include loved ones/family members in tx plans, w/close f/u/monitoring
      • Unfortunately, relatively few DB, placebo controlled trials available for adults with ADHD/SUDs, and data is underwhelming. 34
      • Avoid stimulant rx if pt actively using, consider non-stimulant tx in those in recent recovery (Wellbutrin, Strattera)
      • Extended release preparations are preferred among stimulants (Concerta, Adderall XR, Vyvanse)
          • Clinical data and imaging/binding studies suggest rate of administration correlates with “likability” of stimulants
          • ER vs IR have slower onset curves and are less “likable”
          • ER formulations much harder to crush and then sniff/inject
    • Summary
      • ADHD persists into adulthood and is associated with significant (-) functional impairments
      • ADHD can be difficult to diagnose in adults – but careful dx is essential, with caveat that sxs often present differently
      • ADHD and substance use disorders are each overrepresented in samples of the other
      • In the ADHD/SUD samples, pts have more severe SUDs which are much harder to treat
      • The ADHD/SUD relationship is complex – conduct disorder clearly accounts for some of the overlap, but those with ADHD+CD may represent a more severe phenotype of ADHD/SUD pts
    • Summary
      • The reasons for the ADHD/SUD are not clear although self-medication and/or common biological pathways are leading hypotheses
      • At this time there is no convincing evidence that stimulant treatment increases the risk for SUDs, but also no conclusive evidence of a decreased risk.
      • Stimulant medications are abused/diverted at a fairly high rate, and misuse among those prescribed may be as high as 25%. However, 75% do NOT abuse their meds!
      • Treatment recommendations focus on careful diagnosis, close follow up and careful choice of medication to minimize risks.
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      • Barkley RA. Primary symptoms, diagnostic criteria, prevalence, and gender differences. In: Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. 3rd ed. New York, NY: Guilford Press; 2006: 76-121.
      • Barkley RA. ADHD in Adults. In: Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. 3rd ed. New York, NY: Guilford Press; 2006: 248-296
      • Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 2006; 163:716-723.
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