Dr. Alan Zametkin of the Chesapeake ADHD Center (http://www.chesapeakeadd.com/) presented "The Complex Relationship Between ADHD & Substance Abuse", for the Kolmac School on May 15, 2015 in the Kolmac Clinic - Silver Spring office. It was rated one of the best Kolmac School presentations.

1. ADHD and Substance Abuse
Alan Zametkin MD*
Kristen Moulton
Kathleen Nadeau PhD*
*Chesapeake ADHD Center of MD

2. The Complicated
Relationship
between
ADHD and SUD

5. Prevalence of ADHD in SUD
• 23% *
• Which Substances?
• What diagnostic instrument?
• *Van Emmerick-van OortmerssenK, van de Glind G,
van den Brink W, et al Prevalence of attention deficit
disorder in substance abuse disorder patients: a
meta analysis and meta regression analysis. Drug
Alcohol Depend 2012, 122: 11—9

6. 1) What causes ADHD?
2) What sort of diagnostic mistakes should we be
careful to avoid?
3) What sort of questions are helpful to establish a
diagnosis of adult ADHD? (assuming parental
information is not available or not reliable)

7. 4) How to use stimulants
5) What to do with patients who cannot take
stimulants?
6) Can drugs of abuse cause something similar
to ADHD?
7) Can they treat ADHD?

8. 8) How to deal with the combination of ADHD and
anxiety?
9) How to treat ADHD without medications?
What are the non-pharmacological interventions that
actually have an impact
KIDS VS ADULTS
10) Which books to read? (considering that most
people treat adults and some late adolescents)
for the professional?
for patients?
What about autobiographies of people with ADHD?

9. Attention-Deficit / Hyperactivity Disorder
• Neurodevelopmental disorder that affects both
children and adults
• Persistent pattern of inattention and/or
hyperactivity-impulsivity that impairs daily
functioning
Inattention Hyperactivity Impulsivity
-Difficulty
following
instructions and
completing tasks
-Easily distracted
-Forgetfulness
-Organizational
problems
-Difficulty
remaining still
-Fidgets or
bounces when
seated
-Always seems to
be moving
-Excessive talking
-Difficulty
awaiting turn in
group situations
-Interrupts others
-Blurts out
answers before
questions are
completed

10. Subsyndromal ADHD
• According to the DSM-5, children diagnosed with
ADHD display at least 6 IA or HI symptoms of
disorder, and adults display 5 or more symptoms
• Some individuals display fewer symptoms than
required for diagnosis, yet show comparable
impairment in neuropsychological function
• Subclinical symptoms, particularly inattention,
may still correlate with executive dysfunction
Lin, Chen, & Gau, 2014

11. Potential Confound:
Fetal Alcohol Syndrome
• Children with FAS present with similar
symptoms to ADHD and are often misdiagnosed
• Individuals with FAS show slower development
and function at a younger mental age
• However, maternal alcohol use during
pregnancy is also associated with increased risk
of ADHD
• Some children suffer from both FAS and ADHD
Nauert,
Raldiris,
Bowers, &
Towsey, 2014

12. Causes of ADHD
• No single causal risk factor, but appears to be a
combination of genetics and environment
• Family and twin studies consistently show higher
heritability in those with shared genes
▫ Heritability estimate: ~79%
• Often presents with other neurodevelopmental and
psychiatric problems
• Environmental risks:
▫ Maternal smoking, alcohol, or substance abuse
▫ Family adversity and low income
▫ Nutritional deficiencies, low birth weight and
prematurity
Thapar, Cooper, Jefferies, & Stergiakouli, 2012

13. Diagnosing Adults without Prior Diagnosis
• Skepticism, Skepticism, and more Skepticism
• Mistake #1: Assume previous dx is correct
• Mistake #2: Disregard DSM 5 rules “not better
accounted for another Dx.” (page 60, DSM-5)
• Structured Interview or Rating Scales:
▫ WURS*, Murphy Depaul and Barkley
▫ Wender Utah Rating Scale : see References

15. DEPRESSION
•Sadness
•Fatigue
•Sleep
•Suicidal
Ideation
ANXIETY
DISORDER
•Excessive worry
•Fears
•Avoidance
•Separation/Social
Symptom Overlap
•Poor
concentration
•Restlessness
•Distractibility
ADHD
•Fidgeting
•Impulsive
•Organizational problems

16. Adult Recall of Childhood Sx
• Findings are INCONSISTENT:
• Barkley et al: only 47 % of adults could recall that a
childhood diagnosis existed.
• Only 20 % concordance between parents and adults
diagnosed as children with ADHD
• Manuzza et al: good recall in adulthood (but this was
a clinically referred sample)
• HOWEVER HIGH RATES OF FALSE POSITIVES IN
CONTROLS

17. Assessment of Adults
1. Developmental Hx
2 Clinical Interview R/O all DSM- 5 disorders
3 Outside sources: spouse, parents
4 Previous reports (report cards best)
5 Teen school ratings parent ratings
6 Neuropsych Reports
7 Outside sources

18. Effects of Chronic Marijuana Use
• Greater attention deficits
• Reduced verbal or overall IQ
• Executive dysfunction
• Slower processing speeds
• Poor emotional control, increased impulsivity
**particularly severe cognitive consequences for
early-onset marijuana use (before 16 years old)

19. Effects of other drugs…
• Chronic opiate users show impairments in executive
function and memory
▫ Also show brain structure abnormalities: non-specific
ventricular and cortical volume losses
• Cocaine and other psychostimulant users show
impaired working memory, in addition to
attentional deficits, impaired executive function and
slower response speeds
▫ More specific structural abnormalities, including
losses in the prefrontal and medial temporal lobes
• These drug effects can lead to what appears to be
symptoms of ADHD…

20. What % SUD need Tx for ADHD
20 %**
**2 Kooij SJ, Bejerot S, Blackwell A et al European consensus statement on
diagnosis and treatment of adult ADHD: the European Network Adult ADHD.
BMC Psychiatry 2010; 10: 67. doi: 10.1186/1471-244X-10-67.

21. ADHD leads to SUD
1. Twice as likely to smoke
2. Twice as likely for OH dependence
3. 1.5 as likely to have marijuana dependence
4. Twice as likely to have cocaine dependence
5. 2.5 times as likely to have a SUD

22. Why?
1. ADHD: Impulsivity and Risk Taking
2. ADHD has DAT density/rapid clearance of DA
3. Hence lower DA in synapses
4. Drugs of Abuse: All* increase DA in reward
centers (Nucleus Accumbens)
5. *cocaine stimulants, Ecstasy, nicotine , OH,
opiates, marijuana

23. To Treat ADHD or Not
• Is there evidence to support
pharmacological treatment?
• Is there an argument not to treat?

24. Major Questions?
•Is it safe and effective in treating
ADHD?
•Does it work to treat SUD?

25. Risk of ADHD to Develop SUD
▫Risk is twice normal rates
▫Risk is four times if CONDUCT
DISORDER develops

26. What explains the link?
1. Nicotine improves attention/Exec Fct
2. FUNCTIONAL IMAGING shows both
disorders have Deficits in Ant. Cingulate
and Frontocortical systems
3. DOPAMINE involved in BOTH Disorders

27. Effects of Early ADHD Tx on SUD
• Clearcut: Stimulant Tx does NOT
INCREASE later SUD
• HOWEVER…

28. DOES EARLY TX PREVENT OR REDUCE
LATER SUD
• META-ANALYSIS (Wilens) SHOWED
REDUCED LATER SUD
BUT…
• Later META-ANALYSIS #2 SHOWED
NO EFFECT!

29. IN ADOLESCENTS
• STIMULANT TREATMENT REDUCES SUD
WHILE TREATED
• LESS CRIMINAL ACTIVITY WHILE TREATED
• CD IS A GATEWAY TO SUD

30. IS it safe to Treat ADHD in SUD
• MPD and Cocaine well tolerated
• No EKG findings in interaction between MPD
and Cocaine
• MPD reduced some positive effects of cocaine
• BUT. . . .
• Earlier Literature suggests MPD may
INCREASE CRAVING

31. Actions of MP vs Cocaine
• MPD blocks DA REUPTAKE
TRANSPORTER
• Cocaine blocks DA REUPTAKE
Transporter
• PICTURE HERE

32. Pharmacotherapy:
Receptors
Synapse
Dopamine
Norepinephrine
Nerve
Impulse
Transporter
Tyrosine Hydroxylase
Courtesy of T. Wilens.
Mechanism of Action

33. What does MPD treat in SUD
• Clearly Reduces SX of ADHD (impulsivity)
• Clearly Rarely Reduces SUBSTANCE ABUSE
• WHY????? Anybody’s Guess !!!!!!!
• Treatment for ADHD does not exacerbate SUD

34. Wait for SUD Control Before Treating
ADHD?
• YES: Cannot diagnose ADHD while USING
SUD will prevent response: (Not True)
• Diagnostic uncertainty
• Short acting tx can be abused !
• Exacerbation of non ADHD co morbidity
• Remember: If ADHD exists only during SUD,
IT IS NOT ADHD!!

35. Wait for SUD Control Before Treating
ADHD?
• NO: ADHD treatment will reduce SA (not been
show in research but there are individual
exceptions)
• ADHD is a “causal” factor in SUD (True)
• BUT LONGITUDINAL RESEARCH has NOT
show ADHD Tx to alter the development of SUD
• Pt care is NOT LONGITUDINAL/ Individual

36. 9 Studies of MPD
(Ritalin)
• NOT EFFECTIVE IN TREATING COCAINE
/Nicotine
• Atomoxatine (1 study) reduced Nicotine
Abstinence (non ADHD sample)

37. Treating ADHD in Active SUD
1. Be certain of childhood onset and Dx certainty
2. Use Concerta or Vyvanse (pro drug) or
atomoxatine
3. Careful nursing or significant other
participation
4. Avoid drug seeking or previous stimulant
abusers

38. CONCERTA™: Proof of Product
Develop OROS® Technology

39. CONCERTA™: Proof of Product
Pharmacokinetics
CONCERTA™
provides
–Immediate release
followed by
extended release of
methylphenidate
–Minimized
fluctuations in peak
and trough plasma
concentrations
compared to
methylphenidate tid
N = 36 healthy adults

40. Comprehensive Tx of ADHD/SUD
1. Extended release Ritalin mixed results
2. Buproprion in adults (mixed)
3. CBT: results are not clear cut
4. Contingency mgmt. moderate effect 30 studies

41. Abuse Potential of Tx of ADHD
• High: Dexedrine, Adderall, short-acting Ritalin
• Medium: Ritalin LA, SR, Metadate ,Methylin
Adderall XR
• Low: Vyvance, Intunive, Strattera, Concerta
Buproprion, Daytrana Patch

42. Bottom Line: To Treat or Not
1. Case by case decision-making
2. Degree of diagnostic certainty
3. Risk of diversion or destabilization of other
comorbidity
4. Presence of reliable support and monitoring
5. Previous and current substances abused

43. Discussion Points for TX
1. Proper administration (SUPERVISION)
2. Education about diversion and misuse
3. Transition of care*
4. other administration to self-administration

44. Role of Psychotherapy
• 8 studies show CBT effective for ADHD
symptom reduction when SUD is comorbid
• Since most studies include psychotherapies
alone, UNLCEAR the role of CBT on SUD in
ADHD but 3/10 studies DID show an effect

45. Books for Professionals Tx of Adult
ADHD
1) Ari Tuckman - More Attention, Less
Deficit
2) Kathleen Nadeau- ADD-friendly
Ways to Organize your Life
3) Safren - Mastering your Adult
ADHD
4) Zylowska - The Mindfulness
Prescription for Adult ADHD

46. Non Medication Tx of ADHD
1) Lydia Zylowska's mindfulness meditation -shows
very positive benefit : book : The Mindfulness
Prescription
2) Julia Rucklidge, Ph.D. micronutrients in British
Journal of Psychiatry High doses of a complex
combination of vitamins, minerals and supplements.
3) Steve Safren at MGH: Benefits of Cognitive
Behavioral Therapy in Adult ADHD
4) Mary Solanto Book on CBT for adult ADHD - and
group CBT methods.

52. References:
• Ersche, K. D., Clark, L., London, M., Robbins, T. W., & Sahakian, B. J. (2006).
Profile of executive and memory function associated with amphetamine and
opiate dependence. Neuropsychopharmacology: Official Publication of the
American College of Neuropsychopharmacology, 31(5), 1036–1047.
http://doi.org/10.1038/sj.npp.1300889
• Jovanovski, D., Erb, S., & Zakzanis, K. K. (2005). Neurocognitive deficits in
cocaine users: a quantitative review of the evidence. Journal of Clinical and
Experimental Neuropsychology, 27(2), 189–204.
http://doi.org/10.1080/13803390490515694
• Lin, Y. J., Chen, W. J., & Gau, S. S. (2014). Neuropsychological functions
among adolescents with persistent, subsyndromal and remitted attention
deficit hyperactivity disorder. Psychological Medicine, 44(8), 1765–1777.
http://doi.org/10.1017/S0033291713002390
• Raldiris, T. L., Bowers, T. G., & Towsey, C. (2014). Comparisons of Intelligence
and Behavior in Children With Fetal Alcohol Spectrum Disorder and ADHD.
Journal of Attention Disorders. http://doi.org/10.1177/1087054714563792
• Thapar, A., Cooper, M., Jefferies, R., & Stergiakouli, E. (2012). What causes
attention deficit hyperactivity disorder? Archives of Disease in Childhood,
97(3), 260–265. http://doi.org/10.1136/archdischild-2011-300482

53. THE END

54. DSM-IV ADHD Diagnostic Criteria
A: List of symptoms must be present for past 6
months
B: Some symptoms present before 7 years of age
C: Some impairment from symptoms must be
present in 2 or more settings (eg, school and
home)
D: Significant impairment: social, academic, or
occupational
E: Exclude other mental disorders
American Psychiatric Association. 1994:83-85.

55. DSM-IV Symptoms of Hyperactivity-
Impulsivity
Hyperactivity
• Squirms and fidgets
• Can’t stay seated
• Runs/climbs excessively
• Can’t play/work quietly
• “On the go” / “Driven by a motor”
• Talks excessively
Impulsivity
• Blurts out answers
• Can’t wait turn
• Intrudes/interrupts others
*Must have 6 or more symptoms for at least 6 months to a degree that is maladaptive
and inconsistent with developmental level.
Manifestations of the following symptoms must occur OFTEN*

56. DSM-IV Symptoms of Inattention
Inattention
• Careless
• Difficulty sustaining
attention in activity
• Doesn’t listen
• No follow through
• Avoids/dislikes tasks
requiring sustained
mental effort
• Can’t organize
• Loses important items
• Easily distractible
• Forgetful in daily
activities
*Must have 6 or more symptoms for at least 6 months to a degree that is maladaptive and
inconsistent with developmental level.
Manifestations of the following symptoms must occur OFTEN*