ADHD and Substance AbuseAlan Zametkin MD*Kristen MoultonKathleen Nadeau PhD**Chesapeake ADHD Center of MD

The Complicated Relationship

betweenADHD and SUD

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

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)

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) 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 impactKIDS 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?

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

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 dysfunctionLin, Chen, & Gau,

2014

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, 2014

Raldiris, Bowers, & Towsey, 2014

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

prematurityThapar, Cooper, Jefferies, & Stergiakouli, 2012

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

DEPRESSION

•Sadness•Fatigue•Sleep•Suicidal Ideation

ANXIETY DISORDER

•Excessive worry•Fears•Avoidance•Separation/Social

Symptom Overlap

•Poor concentration•Restlessness•DistractibilityADHD

•Fidgeting•Impulsive•Organizational problems

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

Assessment of Adults

1. Developmental Hx2 Clinical Interview R/O all DSM- 5

disorders3 Outside sources: spouse, parents4 Previous reports (report cards best)5 Teen school ratings parent ratings6 Neuropsych Reports7 Outside sources

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)

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…

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.

ADHD leads to SUD

1. Twice as likely to smoke2. Twice as likely for OH dependence3. 1.5 as likely to have marijuana

dependence4. Twice as likely to have cocaine

dependence5. 2.5 times as likely to have a SUD

Why?

1. ADHD: Impulsivity and Risk Taking2. ADHD has DAT density/rapid clearance

of DA3. Hence lower DA in synapses4. Drugs of Abuse: All* increase DA in

reward centers (Nucleus Accumbens)5. *cocaine stimulants, Ecstasy, nicotine ,

OH, opiates, marijuana

To Treat ADHD or Not

• Is there evidence to supportpharmacological treatment?

• Is there an argument not to treat?

Major Questions?

•Is it safe and effective in treating ADHD?

•Does it work to treat SUD?

Risk of ADHD to Develop SUD

▫Risk is twice normal rates

▫Risk is four times if CONDUCT DISORDER develops

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

Effects of Early ADHD Tx on SUD

•Clearcut: Stimulant Tx does NOT INCREASE later SUD

•HOWEVER…

DOES EARLY TX PREVENT OR REDUCE LATER SUD

•META-ANALYSIS (Wilens) SHOWED REDUCED LATER SUD

BUT…

•Later META-ANALYSIS #2 SHOWED NO EFFECT!

IN ADOLESCENTS

•STIMULANT TREATMENT REDUCES SUD WHILE TREATED

•LESS CRIMINAL ACTIVITY WHILE TREATED

•CD IS A GATEWAY TO SUD

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

Actions of MP vs Cocaine

•MPD blocks DA REUPTAKE TRANSPORTER

•Cocaine blocks DA REUPTAKE Transporter

•PICTURE HERE

Pharmacotherapy:

Receptors

Synapse

DopamineNorepinephrine

NerveImpulse

Transporter

Tyrosine Hydroxylase

Courtesy of T. Wilens.

Mechanism of Action

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

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!!

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

9 Studies of MPD(Ritalin)

•NOT EFFECTIVE IN TREATING COCAINE /Nicotine

•Atomoxatine (1 study) reduced Nicotine Abstinence (non ADHD sample)

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

CONCERTA™: Proof of ProductDevelop OROS® Technology

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

Comprehensive Tx of ADHD/SUD1. Extended release Ritalin mixed results2. Buproprion in adults (mixed)3. CBT: results are not clear cut4. Contingency mgmt. moderate effect 30

studies

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

Bottom Line: To Treat or Not

1. Case by case decision-making2. Degree of diagnostic certainty3. Risk of diversion or destabilization of

other comorbidity4. Presence of reliable support and

monitoring5. Previous and current substances abused

Discussion Points for TX

1. Proper administration (SUPERVISION)

2. Education about diversion and misuse

3. Transition of care*

4. other administration to self-administration

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

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

Non Medication Tx of ADHD1) 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.

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

THE END

DSM-IV ADHD Diagnostic Criteria

A: List of symptoms must be present for past 6 months

B: Some symptoms present before 7 years of ageC: 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.

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*

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*