Assessment and treatment of adolescents and adults with ADHD and SUD

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Assessment and treatment of adolescents and
adults with ADHD and SUD

• Howard Schubiner, MD
• Department of Internal Medicine, Providence
  Hospital
• Southfield, MI
• Clinical Professor, Wayne State University School
  of Medicine
• Detroit, Michigan, USA

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Sudden cardiac death scare in Canada, Feb. 2005

• There were 12 deaths reported in children and
  adolescents in the U.S. between 2001-2004, who
  were taking Adderall (mixed amphetamine salts)
• Adderall was taken off the market by the Canada
  Health Ministry

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Risk of sudden cardiac death with stimulants

• Rates of SCD for Adderall estimated by 10-12
  deaths in children 33 million rxs / 12 months
  per year 0.36 deaths per 100,000 pt-yrs. (0.4
  if use 12 deaths)
• Rates for methylphenidate 7 deaths with 44
  million rxs 0.19 deaths per 100,000 pt-yrs.

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Risk of sudden cardiac death

• 600 sudden deaths per year in children
  (excluding SIDS)
• 300,000/year in adults
• Sudden non-traumatic death accounts for 2-20 of
  all deaths in children age 1-20
• 1.3-8.5 deaths per 100,000 patient years
• Malefemale ratio of 31

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US FDA Response

• The US FDA has issued a warning that stimulants
  should not be used in those with underlying
  cardiac disorders
• Physicians in the US take these warnings
  seriously

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Causes of sudden cardiac death

• Hypertrophic Cardiomyopathy
• Coronary artery anomaly
• Coronary artery disease
• Myocarditis
• RV cardiomyopathy
• Mitral valve prolapse
• Long QT interval
• Aortic dissection

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Adults with markers of Autonomic Nervous System
dysfunction are 3-5 X more likely to die due to
cardiovascular disease
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• Four markers of ANS dysfunction
• Elevated resting heart rate (above 90 bpm).
• Impaired chronotropic response to exercise
  defined as a failure to achieve 85 of
  age-predicted maximal heart rate. Seen in 11-26
  of healthy middle aged adults.
• Heart rate recovery after exercise defined as
  failure to decrease HR by gt12 bpm in the first
  minute after exercise. Occurs in 20 of healthy
  middle aged adults.
• Low HR variability, defined as failure to change
  heart rate (R-R interval) by gt10 beats per minute
  during 1 minute of slow deep breathing. Mayo Clin
  Proc. 2002,7745-54.

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ANS function in ADHD adults

• 30 adults with ADHD on stimulants and 30
  controls underwent exercise stress testing
• 4 of the control group had some abnormalities
  in the ANS in comparison to 24 of the ADHD group
  (p0.052)
• However 24 prevalence is similar to general
  population figures (control group more fit)
• When controlled for METS achieved, small but
  significance differences in HR recovery remained.
  Studies in those on and off stimulants are
  ongoing.
• Schubiner, et. al. J Attention Dis
  200610(2)205-211.

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Risk of stimulant abuse and diversion

• Approx. 7-11 of college students without ADHD
  reported using MPH/AMPH recreationally
  (Klein-Schwartz, McCabe)
• Of 150 non-ADHD students 4 misused AMPH
  compounds, 7 MPH, 24 both, 1/3 admitted to
  using cocaine (Low and Gendaszek)
• Multiple colleges survey 6.9 of students used
  stimulants, 2.1 have used them in the past month
  (McCabe)
• Diversion to young adults without ADHD appears
  problematic

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Risk of stimulant abuse and diversion

• Survey of junior/senior high school students who
  were prescribed stimulants (Poulin et al.)
• --7 sold (diverted) their medications
• Approximately 2/3 using stimulants to study 1/3
  to get high

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Evolution of Therapies for ADHD

• Amphetamines1937
• Methylphenidate1956
• Ritalin SR1967
• Concerta (OROS) MPH2000
• Adderall and XR (mixed amphetamine salts)1996,
  2002
• Focalin and XR (d-MPH)2001,2004

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Non-stimulant Therapies for ADHD

• Wellbutrin (buproprion)1989 Not approved in the
  U.S. for ADHD
• Strattera (atomoxetine)2002 Approved for
  children and adults for ADHD
• Provigil (modafinil)2006 Not approved in the
  U.S. for ADHD

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Emerging Therapies for ADHD

• Daytrana (MPH transdermal patch)2006 Approved
  for children with ADHD
• Vyvanse (Lis-dexamphetamine)2007 Approved for
  children for ADHD

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Methylphenidate Transdermal System (Daytrana)
DOT MatrixTM
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Methylphenidate Pharmacokinetics Transdermal
System
Mean Plasma Concentration of d-methylphenidate
Pierce, et al. Poster presented at AACAP Annual
Meeting October 20, 2005 Toronto, Canada.
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Assessment of ADHD

• Does the individual really have ADHD?
• Careful evaluation is warranted due to higher
  rates of co-morbid conditions which may mimic
  ADHD
• Pay particular attention to childhood history
  and ratings by parents, teachers, and others
• If ADHD is present, what co-morbid conditions
  are also present?
• Assess for anxiety disorders, depression or
  dysthymia, bipolar disorder, ODD/CD

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Assessment of ADHD II

• How are they doing in life? School, work,
  relationships
• Other risk behaviors? Driving safety, sexual
  behaviors, other injury risks
• What are their strengths? Arts, sports,
  electronics, hobbies, clubs, social
• Do they want treatment? Assessment of
  motivation, willingness for treatment, interest
  in achievement in academic and other areas

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Assessment of SUD in individuals with ADHD

• Careful assessment of types of substances used,
  amount and frequency, functional impairments and
  consequences of use
• Severity of SUD and type of drugs involved will
  play a critical role in the management plan

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Development of an honest and caring relationship

• Show interest in them and their activities
• Act as a facilitator to help them define and
  achieve their goals
• Explain options, be honest, expect honesty
• Support motivation and strengths
• Allow them to make choices and give them as much
  control as possible, depending on level of SUD
  and severity of risk behaviors

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Issues in the treatment of ADHD/SUD individuals

• Cardiac risk factors and other medical history
• Treatment options depending on level of SUD
• Risk for diversion and abuse
• Educating patients about diversion and abuse
• Medication treatment and follow up
• Signs of diversion and abuse

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Evaluation of cardiac risk to stimulants and
other ADHD medications

• Family historyof SCD, early MI, congenital
  heart disease, significant arrhythmias
• Personal historyfor heart disease, HTN, chest
  pain, shortness of breath, palpitations, syncope,
  seizures, tics, glaucoma
• Cardiac examrule out significant murmurs
• ECG, Echo, stress test if suspicion of heart
  disease

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Medication options for ADHD/SUD

• Stimulants
• Short, intermediate and long acting
  methylphenidate, including OROS, patch
  technology, d-methylphenidate
• Short and long acting, amphetamine and mixed
  salts amphetamine, lis-dexamphetamine
• Non-stimulants
• Atomoxetine, bupropion, venlafaxine, tricyclics,
  clonidine, guanfacine, modafanil?

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Assessment of risk/severity of SUD in adolescents
and adults with ADHD

• Lower risk groups
• No history of SUD Family history of SUD
  Personal history of SUD (nicotine, alcohol,
  marijuana) in remission Active nicotine SUD
• Moderate risk groups
• Active alcohol SUD active marijuana SUD
  recreational use of cocaine, opiates or other
  drugs, but not SUD
• Higher risk groups
• Current or prior cocaine, opiate, stimulant, or
  prescription drug SUD

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Medical treatment of lower risk ADHD/SUD patients

• Brief office interventions on skills, resources,
  boundaries of use, risks of use
• Warnings regarding diversion
• Monitoring of ADHD response and use/abuse
  patterns
• Family involvement
• Use of stimulants as first line agents due to
  efficacy and safety

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Medical treatment of moderate risk ADHD/SUD
patients

• Above interventions plus
• SUD counseling/office interventions/self-help
  groups
• Toxicology testing as indicated
• More frequent monitoring of use/abuse patterns
  Family treatment as indicated
• Use of stimulants or atomoxetine/bupropion as
  first line agents

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Medical treatment of higher risk ADHD/SUD patients

• All of the above interventions plus
• Rehab program/Contract for continued SUD rx
• Close communication between providers
• May delay ADHD rx until in SUD remission for
  weeks to months
• Use of atomoxetine/bupropion as first line
  agents
• Use of stimulants only under strict supervision

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Minimizing stimulant abuse and diversion

• Cardiac risk screening in all patients and
  explanation of this risk to each patient
• Concern re those without cardiac screening
  receiving stimulants, risk of SCD
• Felony level offenses by giving, loaning or
  selling controlled substances
• Importance of keeping medications hidden/locked

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Use of Medication and Follow up

• Find optimal dosingstart with low doses and
  quickly titrate up to best efficacy without side
  effects
• Tailor dosing to the individuallonger acting
  meds and certain formulations less likely to be
  abused/diverted (e.g. XR,OROS, patch, LDX,
  non-stimulants)
• Frequent visits to monitor ADHD response, SUD
  progress, and overall functioning
• Warn re interaction of OTC drugs, caffeine,
  alcohol, etc.

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Clues for diversion and abuse

• Losing medications
• Urgent requests for refills
• Larger dosing than usual, larger number of pills
• Use of medications documented on automated
  prescription tracking systems

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Conclusions

• SUD is over-represented among those with ADHD
• Treatment of children with ADHD can reduce risk
  of SUD
• Careful assessment of both ADHD and SUD are
  essential
• Treatment of those with ADHD/SUD should be
  tailored to their level of SUD
• Emerging therapies lower the risk of abuse and
  diversion

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