The Complex Relationship between ADHD and Addictions
1
J.J. Rasimas, Ph.D., M.D.
Professor of Psychiatry & Emergency Medicine
Dalhousie University, University of Minnesota, & Penn State College of Medicine
C-L Psychiatry and Addictions, Queen Elizabeth Hospital, Charlottetown, PE
I have no relevant conflicts of interest around
treatments or financial interests related to them
While I have greater exposure to the care of children
than a general psychiatrist, including two years of
supervision under a child psychiatrist, I am not board
certified in CAP
I have formal certification in addiction medicine and
medical toxicology – both make me more attuned to
negative consequences of ingesting things, not
automatically prone to see medicines as therapeutic
2
Appreciate aspects of the complex evolution of
Attention Deficit Hyperactivity Disorder (ADHD)
relevant to addictions
Understand clinically applicable science and care
management principles useful in navigating risks and
benefits of treatment of co-occurring ADHD and
substance use
3
ADHD and Addictions are ”Clinical Diagnoses”
No confirmatory diagnostic tests
◦
No validation outside the assessment(s) of clinician(s)
◦
Expert clinicians agree less than 50% of the time (𝞳)
Symptom criteria and their relevant histories define
disorders
◦
Symptom overlap is common (ADHD and Addictions)
◦
Terminology does not standardize meaning
4
Regier, et al. AJP 2013.
“Clinically”
◦
Some combination of severe inattention, hyperactivity, and
impulsivity that begins in childhood, and often persists into
adulthood
◦
Must cause functional impairment across settings, and must
be developmentally relevant
◦
Symptoms must be present before age 7
“Neurobiologically”
◦
A condition of abnormal central neurologic development
partially determined by genetics
◦
Differences in brain morphology reflect neurodevelopment
that can be altered by “nurture” and treatment
5
Spinelli, et al. JAACAP 2011.
Ogrim, et al. Psych Res 2012.
Peak cortical thickness for ADHD and healthy controls:
ADHD
“shift to the right”
Shaw et al. Attention-deficit/hyperactivity disorder is characterized
by a delay in cortical maturation.
PNAS
,
104(49): 19649-19654
Not a thing.
7
Diagnosis is observer-based
◦
Rater bias (including agendas desirous of answers)
◦
With input from multiple sources (parents, teachers, etc.)
reliability is moderate – Connors or other tools can help
Criteria modification with increasing age is not standard
Retrospective views of symptoms by adults, especially
without collateral information are even less reliable
◦
Especially when reported by an individual who has current
suffering and a wish for treatment to soothe it
8
Like all things in medicine, early recognition and
intervention for ADHD is best
Recommendations are grouped by age
◦
4 to 5, behaviour therapy is first line Tx.
◦
6 to 11, stimulant medication
AND
behaviour therapy, along with
accommodations at school to address special needs.
◦
12 to 18, medication with the teen’s consent and participation,
AND
behaviour therapy.
Psychostimulants are the most efficacious
AND
come with
the greatest potential for adverse effects
◦
Atomoxetine, viloxazine, bupropion, TCAs, SSRIs
◦
Clonidine / Guanfacine typically adjunctive (hyperactive subtype)
9
American Academy of Pediatrics
Wang, et al. Plos One 2013.
Large studies of clinically applicable populations indicate
childhood Rx with stimulants does not ”cause addiction”
Robust treatment for ADHD in childhood reduces the
risk of development of clinically evident addictive illness
◦
Up to 50% in youth
◦
At least 15% (perhaps up to 60%) in adolescents / adults
10
Faraone & Wilens. JCP, 2013.
Chang, et al. JCPP 2014.
McCabe, et al. JAACAP 2016.
Addictive disorders have genetic determinants that can
alter risk-benefit profiles with substandard treatment.
Psychostimulant mechanism strikes a key chord in the
limbic music of emotion, reward, and addiction
◦
Increase the amount and persistence of monoamines
(dopamine, norepinephrine, even serotonin) in synaptic clefts
Blockade of DA and NE transporters (reuptake)
Enhance release of catecholamines from presynaptic vesicles
11
Seek an accurate diagnostically-relevant history for
ADHD
Distinguish withdrawal anxieties, sleep inefficiencies,
and other substance-related symptoms
Screen also for comorbid conditions with overlapping
symptoms
◦
PTSD
◦
Anxiety Disorders
◦
Mood Disorders (both depression and (hypo)mania)
◦
Psychosis
12
Mariani & Levin. AM J Addict 2007.
13
Longitudinal NIH Cohort – Followed ~ 2 decades
Giedd, 2010.
Age (yrs)
Cortical Thickness (mm)
G
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o
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O
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o
m
e
T
y
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a
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l
y
D
e
v
e
l
o
p
i
n
g
P
o
o
r
O
u
t
c
o
m
e
Giedd, 2010.
Evidence base is not solid
◦
Clinical expertise and prudence define guidelines
Retain principles of therapy from youth treatment
Atomoxetine, viloxazine (NRIs)
◦
make the most mechanistic sense
TCAs, SNRIs, SSRIs
Bupropion (NDRI)
Modafinil
Clonidine / Guanfacine
15
Mariani & Levin. AM J Addict 2007.
Methylphenidate – rational first choice of compound
◦
Utility of routine urine screening immunoassays
◦
Preparations are not well-protected against diversion
All other stimulants are close structural analogs with
basic amphetamine
◦
Lisdexamfetamine may be the best choice to avoid diversion
Methamphetamine…
16
Mariani & Levin. AM J Addict 2007.
Methylphenidate
17
Bupropion
(Wellbutrin)
29 y/o man — “substance use history”
Delivered by police after neighbors called
◦
Loud disturbance, pounding on walls
◦
Found shirtless, violent with police
◦
Restrained…Multiple doses of sedative medication
Elevated body temperature and blood pressure
◦
Evidence of kidney damage and heart stress
Three days in ICU
◦
Paranoia — robot rats in the walls at home
◦
Took
“Crystal Meth”
to “Get sh** done”
Antipsychotic medications given
Inpatient Psychiatry
Transferred to inpatient addiction recovery weeks later
18
Crosses into and stays in the brain longer than cocaine and
other stimulants
Depletes nerve cells of dopamine and other transmitters
◦
Rush of these chemicals cause the high
◦
Psychosis and dysregulated behaviour
Overstimulation and subsequent lack of transmitters,
nutrients, and integrity causes stress on nerve cells…
sometimes to the point of death
19
Memory, concentration, impulse control, judgment
◦
Greater risk of dementia (earlier)
Anxiety, Depression, Psychosis
◦
Paranoia, Formication
Uncontrolled and / or repetitive movements
◦
Punding (purposeless compulsions)
Dental caries, bruxism (jaw clenching/grinding), acne / skin
breakouts, heart and lung disease,…
20
21
Scylla
Charybdis
Early recognition and treatment for ADHD prevents the
development of substance use disorders
◦
Alcohol, cannabis, stimulants, and even sedatives / opioids
◦
First line treatment is stimulant medication
Once addiction has taken hold, patients need to participate
in psychotherapies to recover
◦
Untreated ADHD symptoms may obstruct the process
Prescribing stimulants may fuel addiction and / or
exacerbate other psychiatric problems (e.g. psychosis)
◦
Nonstimulant medications are “first-line” but often work less well
22
Jay Giedd, M.D. – NIH / UCSD
J. Ward Donovan, M.D. – Penn State / Pinnacle Toxicology
Dan Rusyniak, M.D. – Indiana University
Charlie Reznikoff, M.D. – Hennepin County Medical Center
erowid.org
23
COMMENTS / QUESTIONS ???
24
Endogenous phenethylamines are derivatives of
tyrosine
◦
Dopamine
◦
Norepinephrine
Exogenous phenethylamines
◦
Stimulate dopamine and noradrenergic receptors
◦
Stimulate catecholamine release
◦
Stimulate serotonin receptors
25
26
Lipophilic substitution of the side chains of this core
ephedrine
structure is associated with varying
degrees of
hallucinogenic
and
stimulatory
effect.
27
Cocaine
Monoamines
MAT
1
2
Serotonergic
Neuron
LSD
5-HT
2
receptors
3
Stimulants:
1
inhibitors
2
substrates
Psychedelics:
3
5-HT
2A
agonists
Rx Psychotropics:
4
Reuptake inhibitors
MDMA
4
(SND) RIs
Intensity
28
29
30
Impact of use of meth and newer “designer” stimulant
drugs on brain function and mental health make it difficult
to engage patients in standard addiction treatment
◦
Cognitive impairments, impulse control problems, paranoia, etc.
No current evidence-based medication treatments for
addiction to stimulants
◦
Unlike alcohol, opioids
Comorbid Attention-Deficit Hyperactivity Disorder
(ADHD)
◦
Pre-existing illness vs. similar impairments caused by drug use
31
Hi, I’m J.J. Rasimas.
I wonder if the idea from this subtitle resonates right away – a clinical Odyssey can be threatened on multiple sides, sometimes simultaneously, like the dangers of the strait that separates Sicily from the Italian Peninsula. That’s where these mythical Homeric figures are thought to have lived. The illnesses we are dealing with are quite real, but their threat can be as big as the myth of this monstrous hydra and this gaping whirlpool.
This certainly is a challenging clinical landscape for which I’ll use the time I have today to give a survey, highlighting some issues I think are particularly important.
But, there is enough to be concerned about here to have a whole dedicated subspecialty training program and corresponding medical practices designed to address what we’ll touch on in 45 minutes.
With those limitations in mind, I have confessions to make about what I’ll say…
Appreciate the intricate evolution of Attention Deficit Hyperactivity Disorder (ADHD) in relation to addictions. Explore clinically relevant science and care management principles for managing co-occurring ADHD and substance use. ADHD and addictions are clinical diagnoses with no definitive tests, highlighting the importance of understanding symptom criteria and relevant histories. Dive into the clinical presentation of ADHD, emphasizing the neurobiological basis and developmental factors.
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Presentation Transcript
J.J. Rasimas, Ph.D., M.D. Professor of Psychiatry & Emergency Medicine Dalhousie University, University of Minnesota, & Penn State College of Medicine C-L Psychiatry and Addictions, Queen Elizabeth Hospital, Charlottetown, PE 1
I have no relevant conflicts of interest around treatments or financial interests related to them While I have greater exposure to the care of children than a general psychiatrist, including two years of supervision under a child psychiatrist, I am not board certified in CAP I have formal certification in addiction medicine and medical toxicology both make me more attuned to negative consequences of ingesting things, not automatically prone to see medicines as therapeutic 2
Appreciate aspects of the complex evolution of Attention Deficit Hyperactivity Disorder (ADHD) relevant to addictions Understand clinically applicable science and care management principles useful in navigating risks and benefits of treatment of co-occurring ADHD and substance use 3
ADHD and Addictions are Clinical Diagnoses No confirmatory diagnostic tests No validation outside the assessment(s) of clinician(s) Expert clinicians agree less than 50% of the time (?) Symptom criteria and their relevant histories define disorders Symptom overlap is common (ADHD and Addictions) Terminology does not standardize meaning Regier, et al. AJP 2013. 4
Clinically Some combination of severe inattention, hyperactivity, and impulsivity that begins in childhood, and often persists into adulthood Must cause functional impairment across settings, and must be developmentally relevant Symptoms must be present before age 7 Neurobiologically A condition of abnormal central neurologic development partially determined by genetics Differences in brain morphology reflect neurodevelopment that can be altered by nurture and treatment Spinelli, et al. JAACAP 2011. Ogrim, et al. Psych Res 2012. 5
Peak cortical thickness for ADHD and healthy controls: ADHD shift to the right Shaw et al. Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. PNAS, 104(49): 19649-19654
Diagnosis is observer-based Rater bias (including agendas desirous of answers) With input from multiple sources (parents, teachers, etc.) reliability is moderate Connors or other tools can help Criteria modification with increasing age is not standard Retrospective views of symptoms by adults, especially without collateral information are even less reliable Especially when reported by an individual who has current suffering and a wish for treatment to soothe it 8
Like all things in medicine, early recognition and intervention for ADHD is best Recommendations are grouped by age 4 to 5, behaviour therapy is first line Tx. 6 to 11, stimulant medication AND behaviour therapy, along with accommodations at school to address special needs. 12 to 18, medication with the teen s consent and participation, AND behaviour therapy. Psychostimulants are the most efficacious AND come with the greatest potential for adverse effects Atomoxetine, viloxazine, bupropion, TCAs, SSRIs Clonidine / Guanfacine typically adjunctive (hyperactive subtype) American Academy of Pediatrics Wang, et al. Plos One 2013. 9
Large studies of clinically applicable populations indicate childhood Rx with stimulants does not cause addiction Robust treatment for ADHD in childhood reduces the risk of development of clinically evident addictive illness Up to 50% in youth At least 15% (perhaps up to 60%) in adolescents / adults Addictive disorders have genetic determinants that can alter risk-benefit profiles with substandard treatment. Faraone & Wilens. JCP, 2013. Chang, et al. JCPP 2014. McCabe, et al. JAACAP 2016. 10
Psychostimulant mechanism strikes a key chord in the limbic music of emotion, reward, and addiction Increase the amount and persistence of monoamines (dopamine, norepinephrine, even serotonin) in synaptic clefts Blockade of DA and NE transporters (reuptake) Enhance release of catecholamines from presynaptic vesicles 11
Seek an accurate diagnostically-relevant history for ADHD Distinguish withdrawal anxieties, sleep inefficiencies, and other substance-related symptoms Screen also for comorbid conditions with overlapping symptoms PTSD Anxiety Disorders Mood Disorders (both depression and (hypo)mania) Psychosis Mariani & Levin. AM J Addict 2007. 12
Full remission (21%) Partial (42%) No improvement (37%) Longitudinal NIH Cohort Followed ~ 2 decades Giedd, 2010. 13
Typically Developing Cortical Thickness (mm) Good Outcome Poor Outcome Age (yrs) Giedd, 2010.
Evidence base is not solid Clinical expertise and prudence define guidelines Retain principles of therapy from youth treatment Atomoxetine, viloxazine (NRIs) make the most mechanistic sense TCAs, SNRIs, SSRIs Bupropion (NDRI) Modafinil Clonidine / Guanfacine Mariani & Levin. AM J Addict 2007. 15
Methylphenidate rational first choice of compound Utility of routine urine screening immunoassays Preparations are not well-protected against diversion All other stimulants are close structural analogs with basic amphetamine Lisdexamfetamine may be the best choice to avoid diversion Methamphetamine Mariani & Levin. AM J Addict 2007. 16
Methylphenidate Dopamine Norepinephrine Methamphetamine Amphetamine Bupropion (Wellbutrin) 17
29 y/o man substance use history Delivered by police after neighbors called Loud disturbance, pounding on walls Found shirtless, violent with police Restrained Multiple doses of sedative medication Elevated body temperature and blood pressure Evidence of kidney damage and heart stress Three days in ICU Paranoia robot rats in the walls at home Took Crystal Meth to Get sh** done Antipsychotic medications given Inpatient Psychiatry Transferred to inpatient addiction recovery weeks later 18
Crosses into and stays in the brain longer than cocaine and other stimulants Depletes nerve cells of dopamine and other transmitters Rush of these chemicals cause the high Psychosis and dysregulated behaviour Overstimulation and subsequent lack of transmitters, nutrients, and integrity causes stress on nerve cells sometimes to the point of death 19
Memory, concentration, impulse control, judgment Greater risk of dementia (earlier) Anxiety, Depression, Psychosis Paranoia, Formication Uncontrolled and / or repetitive movements Punding (purposeless compulsions) Dental caries, bruxism (jaw clenching/grinding), acne / skin breakouts, heart and lung disease, 20
Scylla Charybdis 21
Early recognition and treatment for ADHD prevents the development of substance use disorders Alcohol, cannabis, stimulants, and even sedatives / opioids First line treatment is stimulant medication Once addiction has taken hold, patients need to participate in psychotherapies to recover Untreated ADHD symptoms may obstruct the process Prescribing stimulants may fuel addiction and / or exacerbate other psychiatric problems (e.g. psychosis) Nonstimulant medications are first-line but often work less well 22
Jay Giedd, M.D. NIH / UCSD J. Ward Donovan, M.D. Penn State / Pinnacle Toxicology Dan Rusyniak, M.D. Indiana University Charlie Reznikoff, M.D. Hennepin County Medical Center erowid.org COMMENTS / QUESTIONS ??? 23
Endogenous phenethylamines are derivatives of tyrosine Dopamine Norepinephrine Exogenous phenethylamines Stimulate dopamine and noradrenergic receptors Stimulate catecholamine release Stimulate serotonin receptors 25
Lipophilic substitution of the side chains of this core ephedrine structure is associated with varying degrees of hallucinogenic and stimulatory effect. 26
Stimulants: 1 inhibitors 2 substrates Serotonergic Neuron Monoamines Psychedelics: 3 5-HT2A agonists 2 (SND) RIs Rx Psychotropics: 4 Reuptake inhibitors 4 MAT 1 Cocaine LSD 3 MDMA 5-HT2 receptors 27
Stimulant Binge Architecture 14 12 10 8 Intensity 6 4 2 0 Time 1 Time 2 Time 3 Time 4 Euphoria Dysphoria Toxicity 28
Early binge Mid-binge Toxicity Alert Sexy/flirtatious Energetic Confident Chatty Awake Euphoric Vigilant Adventurous Jittery Bold Verbose Up late Need a bump Paranoid Hypersexual Agitated Aggressive Pressured Insomniac Dysphoric 29
Crack Cocaine Meth 30 min 2 hours 8 hours 12 36 5 days hours hours 30
Impact of use of meth and newer designer stimulant drugs on brain function and mental health make it difficult to engage patients in standard addiction treatment Cognitive impairments, impulse control problems, paranoia, etc. No current evidence-based medication treatments for addiction to stimulants Unlike alcohol, opioids Comorbid Attention-Deficit Hyperactivity Disorder (ADHD) Pre-existing illness vs. similar impairments caused by drug use 31
