ADHD and Addiction: Diagnosis and Management

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ADHD and Addiction Diagnosis and Management
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Outline

1. ADHD diagnosis and complications of diagnosis
2. ADHD epidemiology and comorbid conditions
3. ADHD and substance use disorder (SUD)
   epidemiology
4. Association between ADHD and SUDs determining
   causality and functional impact
5. Potential explanations for the ADHD/SUD
   association
6. Stimulant treatment and the risk for SUDs
7. Diversion and misuse of stimulant medications
8. Treatment recommendations

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Making the ADHD diagnosisDSM criteria
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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

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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

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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 (66)

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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

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Making the ADHD diagnosis(clinical reality!)

• Sxs in adults can present differently1
• 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 dxd 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 ADHD2

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Making the ADHD diagnosis(clinical reality!)

• 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

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Epidemiology of ADHD

• Attention-Deficit Hyperactivity Disorder (ADHD)
  prevalence is approx. 3-7 in school age
  children3
• 75 of children continue to have sxs into
  adolescence, approximately 50 into adulthood4
• Adult prevalence is estimated to be 3-55
• ADHD is over-represented in substance abusing
  populations and SUDs similarly in adults with ADHD

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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 adolescents6

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ADHD and SUD comorbidity

• NCS-R data5
• 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 ADHD8
• Cocaine dependent pts 10-358
• EtOH dependent pts 33-718

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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

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Rethinking old data, and new research

1. The role of conduct d/o
2. ADHD symptom dimensions vs categorical diagnosis
3. Specific substances of abuse/dependence

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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 Lynams 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 alone11
• 2 subsequent prospective studies support this
  trend
• August et al. (2006)12 ADHDCD group at higher
  risk for SUD, but risk disappears when CD
  controlled for
• Barkley et al. (2004)13 also ADHDCD with
  increased risk, and not ADHD alone, although ADHD
  severity independently linked to drug related
  antisocial activity

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Conduct Disorder A complicating
factor?(continued)

• To the contrary
• Even within the body of data reviewed by Flory
  and Lynam11 , 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.
• CDADHD more use and problems.

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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 dxd
  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

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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

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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

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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

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ADHD and Substance Abuse Potential biological
pathways

• Preliminary research
• Adults with ADHD have been found to have
  decreased DA synthesis/metabolism in prefrontal
  cortex18 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 putamen21,22

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Relationship between stimulant treatment and SUDs

• Does stimulant tx decrease, increase or have no
  effect on the risk of developing a SUD?

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Relationship between stimulant treatment and SUDs

• 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 adults22
• 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 SA23

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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 SUDs24
• Only 6 studies included
• Protective effect much greater on adolescent use
  than adult use
• Why?
• Adolescents more closely monitored by parents?
• Adolescents hadnt passed through full risk
  period?

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Relationship between stimulant treatment and SUDs

• More recent studies
• Faraone et al. (2007)25 retrospective data in
  adults with ADHD (n206), 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

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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.

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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/diversion29
• Among college students lifetime prevalence of
  stimulant misuse between 6-1630, 31, 32
• More likely to be white, male, fraternities/sorori
  ties and lower grades
• In Biedermans 10-year prospective study of boys
  with ADHD, 22 admitted misusing their
  medications, 11 diverting33
• 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

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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

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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 ADHDCD may represent a
  more severe phenotype of ADHD/SUD pts

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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.