Attention Deficit Hyperactivity Disorder and AddictionLaura Ferguson MD, Hazelden

Agenda ADHD and Addiction

• Case Study

• History of ADHD

• Assessment and Diagnosis

• Epidemiology

• Genetics

• Neurobiology

• Treatment

Case Study of “Joe”

• 31 year old man with history of methamphetamine and alcohol dependency, off meth x 3 years and EtOH x 2 years presents with c/o mood swings, irritability, impulsivity, and inattention probs. Currently wanting to go back to school for RT, but worries his symptoms will prevent him from reaching his goals.

• As adult has periods of increased impulsivity, irritability, reduced need for sleep, racing thoughts, and risk taking behaviors (fighting) lasting 1-2 days and depressions lasting 1-2 days.

• Childhood history of hyperactivity, inattention, poor grades, truancy, legal issues, and conflicts at home.

• What might Joe’s problem be?

History of ADHD

• Originally identified by Dr. George Still in the early 20th

century - described children with emotional lability, aggression, defiance, disinhibition, and inattention. Called it “deficient rule governing behavior” and considered a “defect of moral control”.

• Early research looked at brain insults to the frontal lobe, but saw pts w/o brain damage with similar symptoms.

• Hyperactivity most emphasized symptom until the 70’s until Dr. Virginia Douglas looked at daydreaming and lack of focus and hyperactivity… “Attention Deficit Hyperactivity Disorder”.

History of ADHD

• Originally identified by Dr. George Still in the early 20th

century - described children with emotional lability, aggression, defiance, disinhibition, and inattention. Called it “deficient rule governing behavior” and considered a “defect of moral control”.

• Early research looked at brain insults to the frontal lobe, but saw pts w/o brain damage with similar symptoms.

• Hyperactivity most emphasized symptom until the 70’s until Dr. Virginia Douglas looked at daydreaming and lack of focus and hyperactivity… “Attention Deficit Hyperactivity Disorder”.

Diagnosis of ADHD

• DSM-IV-TR criteria– Diagnostic criteria for Attention-Deficit/Hyperactivity

Disorder…primarily inattentive type, primarily hyperactive type, or combined type

– A. Either (1) or (2):(1) inattention: 6 (or more) of the following symptoms of inattention have persisted for 6 months+ to a degree that is maladaptive and inconsistent with development level

(a) often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities

(b) often has difficulty sustaining attention in tasks or play activities

(c) often does not seem to listen when spoken to directly

Diagnosis of ADHD

Inattention continued

(d) often does not follow through on instructions and fails to finishschool work, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions)

(e) often has difficulty organizing tasks and activities

(f) often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (such as schoolwork or homework)

(g) often loses things necessary for tasks or activities (e.g., toys, school assignments, pencils, books, or tools)

(h) is often easily distracted by extraneous stimuli

(i) is often forgetful in daily activities

Diagnosis of ADHD

– (2) hyperactivity-impulsivity: 6 (or more) of the following symptoms of hyperactivity-impulsivity have persisted for 6 months+ to a degree that is maladaptive and inconsistent with development level

• Hyperactivity(a) often fidgets with hands or feet or squirms in seat(b) often leaves seat in classroom or in other situations in which remaining seated is expected(c) often runs about or climbs excessively in situations in which it is inappropriate (in adolescents or adults, may be limited to subjective feelings of restlessness)(d) often has difficulty playing or engaging in leisure activities quietly(e) is often "on the go" or often acts as if "driven by a motor"(f) often talks excessively

Diagnosis of ADHD

• Impulsivity(g) often blurts out answers before questions have been completed(h) often has difficulty awaiting turn(i) often interrupts or intrudes on others (e.g., butts into conversations or games)

B. Some hyperactive-impulsive or inattentive symptoms that caused impairment were present before age 7 (if not then consider ADHD NOS diagnosis)

C. Some impairment from the symptoms is present in 2 or more settings (e.g. at school, work, home)

D. There must be clear evidence of clinically significant impairment in social, academic, or occupational functioning

E. 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

Other Symptoms of ADHD

• Emotional Dysregulation– Deficient Emotional Self-Regulation (DESR) in adults, topic of

exploration in recent studies

– DESR more common with ADHD adults than non ADHD adults

– Symptoms of low frustration tolerance, impatience, temper outbursts, over-reactive, easily frustrated, easily excited, and emotional lability

Other Symptoms of ADHD

• Emotional Dysregulation contined

– DESR greater severity of symptoms in ADHD versus controls and associated with significant morbidity and distress

– Functional/social impairment in multiple domains – education, work, money management, peers, marriage, parenting, driving, legal, and leisure activities

Other Symptoms of ADHD

• Insomnia - independent of other co-morbid diagnosis– Circadian Rhythm DO

ADHD vs controls - incr. c/o sleep onset insomnia and sleep study documented falling asleep and waking up later even when no c/o insomnia compared to controls (Van Veen et al)

– Do medications worsen insomnia?Post hoc analysis of 2 random, parallel-group, double-blind, placebo-controlled studies of Vyvance- no significant change in sleep quality or an improvement from baseline (Weisler et al)

Epidemiology of ADHD

• Epidemiology– ADHD one of most common diagnosis: 8-9% of school aged

children and 4.4% adults

– Worldwide prevalence of ADHD 5.3%

– Up to 60% persistence of ADHD into adulthood

– If diagnosis in childhood, male>female but rates about equal between genders when diagnosed as adults

Epidemiology of ADHD

• 78.68% females and 74.78% males with ADHD have 2+ Axis I diagnosis

• Percent with 2nd diagnosis and number of diagnosis increase with age

• 60% ADHD children have co-morbid oppositional defiant DO (ODD) and 19% conduct DO

• 50% of children with Tourette’s also have ADHD

• ADHD adults can see anxiety, depression, bipolar, cluster B personality DO (borderline/antisocial)

ADHD and Substance Abuse

• 17-45% have co-morbid ETOH abuse/dependence (Goodwin, et al and Tarter, et al showed 70% prevalence)

• In one study, Biederman et al….– Cannabis 67%

– Cocaine 23%

– Other stimulants 18%

• Prevalence is higher in adults with ADHD than adolescents

• Peak of SUD in ADHD patients seen at 20 years old

Causes for ADHD Symptoms

• Most likely a combination of genetics plus environment

• See differences in brain structure, neurotransmitters (dopamine, norepinephrine, and possibly serotonin), and brain function in the prefrontal cortex down to the subcortical areas

Genetics of ADHD

• 60-95% heritability in twin/adoption studies, as high or higher than other diagnosis

• Monozygotic (identical) twins more likely than dizygotic(fraternal) twins

• Family studies suggest the Relative Risk (RR) for ADHD diagnosis in parents or siblings is 4-6 x greater

• RR is higher when symptoms persist into teens

Genetics of ADHD

• Genetic studies suggest 7+ genes may be associated with ADHD– Encode parts of the neurotransmitter signaling system

– Most noted the DA (dopamine) and NE (norepinephrine) neurotransmitter system, decreased in ADHD

• NE involved in attention, arousal, mood

• DA involved in reward systems, impulsivity, modulation of mood

– Polymorphism in DA-beta hydroxylase -> deficit in attention (converts DANE)

– DA - 4/5 receptor and DA transporter gene (DAT)

– Serotonin transporter/receptor genes also implicated

Neurobiology of ADHD

Neurobiology of ADHD

• PET - injection or inhalation of radioactive material and measure distribution in brain

• In ADHD have seen – Changed frontostriatal function with decreased DA release in

caudate and limbic regions

– Decreased activity in reward processing and motivation areas, nucleus accumbens, and caudate

– Decreased activity of DA in hypothalamus (sleep problems, obesity, abnormal reaction to stress?)

Neurobiology of ADHD

ADHD brain---neurons less active

Normal brain—neurons more active

PET Scan

Neurobiology of ADHD

• Functional MRI looks at brain activity at rest and during task– Differences in working memory, executive function, cognitive

control, reward processing, task switching, and attention

• Structural MRI looks at brain structures– Certain brain structures that are involved in attention,

processing, and impulsivity maybe smaller in size in ADHD pts• Right prefrontal cortex (PFC)

– Lesions to the right PFC in animals-ADHD symptoms

• Caudate nucleus, Globus pallidus, Cerebellum and other hypothesized areas (e.g. parietal cortices, cingulate gyrus)

Environmental Risks for ADHD

• Unlikely to be any one environmental cause, may increase risk with underlying genetic risk– Exposure to polychlorinated biphenyls

– Fetal exposure to EtOH/drugs

– Prenatal maternal smoking

– Complications of pregnancy and delivery

– Psychosocial adversity

Testing for ADHD

• Several scales available– Brown ADD scale

• Measures a host of symptoms beyond inattentive criteria

– ADHD rating scale• Based on DSM-IV criteria

– Conners adult ADHD rating scale• Inattention/hyperactivity/impulsivity

– Diagnostic interview schedule-IV section L (DIS-L)• Retrospectively looks at DSM-IV childhood ADHD criteria in

adults

– Others

Treatment of ADHD with Drug Dependence

• Some studies suggest that children treated for ADHD have lower likelihood of SUD, others suggest no protective or worsening risk of SUD with stimulant treatment

• Some studies suggest treatment of adults with ADHD/SUD may reduce the risk of relapse, others suggest no reduction in relapse

• Patients with ADHD and SUD have earlier age of onset of SUD, may take longer to remission, and may have higher rates of other psych comorbidities

Treatment of ADHD with Drug Dependence

• Studies suggest that children are abusing prescription drugs in higher and higher numbers

• Many get the drugs from friends or their parent’s medicine cabinet

• Many adults in treatment at Hazelden have endorsed abusing their stimulants, sharing with friends, or selling them for other drugs as children/teens/adults

• Highest risk for abuse of stimulants is in individuals with previous SUD

ADHD and Drug Dependence

• Himanshu P. Managing Attention Deficit/Hyperactivity Disorder in the presence of substance use disorder. Journal of Clinical Psychiatry 2007; 68 (suppl 11): 23-30

- Review article looked at 16 studies (6 case reports, 4 open label, and 6 double blind)

- 3/6 looked at methylphenidate use for ADHD with h/o cocaine, alcohol, or varied drug use (others looked at use of pemoline, bromocriptine, bupropion, and methylphenidate treatment in methadone patients with ADHD)

- None saw decreased drug use with methylphenidate, except one showed possible reduction of cocaine use over time with treatment

- None showed worsening of drug/EtOH use with methylphenidate

What about “Joe”?

• Unable to get improvement of ADHD with trials of Effexorand Wellbutrin (Strattera not available)

• Really struggling in school and C&S for 4 years+ from everything

• Very compliant and had family support

• Started Ritalin and was doing better in school, more hopeful, less anxious, and less depressed

What about “Joe”?

• Very busy with school and later with work so difficult to make it in for appointments

• Then c/o more anxious, depression, and not sleeping

• Later found he had relapsed to drinking and was abusing Ritalin

• Stopped Ritalin and referred back into SUD treatment, but no follow through

• Lessons Learned?

Treatment of ADHD and Drug Dependence

• Start with non-stimulants especially if still using or newly C&S

• If non-stimulant meds fail, use extended release stimulants such as methylphenidate (Ritalin/Concerta) - may reduce the risk of misuse or diversion (ALL have been abused)

• Close monitoring - frequent visits, non-judgmental, supportive dialogue along with explanations for limit setting helps build trust

• Random urine drug screens• Small quantities of pills and pill counts• Warn patients to store medications safely “NO early refills”

Treatment of ADHD and Drug Dependence

• Red Flags– Demanding IR products

– Discordant pill counts

– Multiple requests for early refills

– Psychosis, moodiness, or changes in mental status

– C/o palpitations, syncope, and shortness of breath

Non-Stimulant Medications

• Antidepressants with NE/DA effects – Ex. venlafaxine (Effexor), desipraminine (Norpramin),

bupropion (Wellbutrin) and duloxetine (Cymbalta)

• Atomoxetine (Strattera) only non-stimulant indicated for ADHD, also NE effects– Likely to take longer to get effect than stimulants, up to 6-8

weeks

– Side effects similar to stimulants

– Expensive so some insurance issues

Non-Stimulant Med Studies

• Burpopion - helpful for ADHD and may help Meth dependence in smaller quantity users (randomized, placebo cont study in ADHD saw 30% reduction of symptoms in 70% of subjects)

• Desipramine - found to be helpful in study of adults with ADHD (randomized, placebo cont response rate 68%)

• Atomoxitine (Strattera) - found more effective than placebo for adults in 2 studies with >500 adults

Other Non-stimulant Options

• Clonidine XR (Kapvay) or guanfacine XR (Intuniv) approved for children (with stimulants) for residual ADHD symptoms, also helpful for ODD symptoms

• Possible dietary changes for intolerance to foods or food additives for children (Elimination Diet)

• CBT and Meta-cognitive training for adults– 12 wk, manualized group treatment for organization, time

management, and planning skills

Summary

• ADHD is a common disorder that tends to run in families• Causes are multifactorial - genetics and environmental• Presents in childhood, often with emotional lability and

interpersonal, educational, career difficulties • Highly co-morbid with SUD and other Axis I diagnosis• Not treating ADHD could increase risk of SUD or relapse to

substance use• ADHD co-morbid with SUD is challenging due risk of abuse of

stimulant drugs or relapse to other drugs• Few stimulant studies with SUD, mixed results, but recommend

use of non-stimulant options first• Co-morbid ADHD + SUD folks need close monitoring and lots of

support

References

• Biederman J. et al. Stimulant therapy and risk for subsequent substance use disorders in male adults with ADHD: A naturalistic controlled 10-year follow-up study. Am J Psychiatry. 2008;165:597-603

• Brennan AR, Arnsten AET. Neuronal mechanisms underlying attention deficit hyperactivity disorder, the influence of arousal on prefrontal cortical function. Annals of New York Academy of Sciences. 2008;1129:236-245

• Faraone SV, Antshel KM. Diagnosing and treating attention-deficit/hyperactivity disorder in adults. World Psychiatry. 2008;7:131-6

• Kollins S. ADHD from the inside out: Genetics, neuroimaging, and implications for treatment. Medscape Education Psychiatry & Mental Health. 12/17/2010

• Prince J. Catecholamine dysfunction in attention-deficit/hyperactivity disorder, an update. Journal of Clinical Psychopharmacology. 2008;28(3):S39-44