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,
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.

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ADHD and Addiction: Diagnosis and Management

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