Transcript Masters Series Anissa Abi-Dargham MD Professor of Clinical

Ethical implications of mental health care and
institutionalization
Nina B. Urban, MD, MSc, FAPA
Assistant Professor of Psychiatry
Columbia University
Division of Substance Abuse
Global Bioethics Summer School, NYC
July 2, 2015
Disclosures
• No conflicts of interest to report
Overview
•
•
•
•
•
Dopamine & addiction
PET imaging
Opioids
Drug laws and outcomes
Treatment options
Overview
•
•
•
•
•
Dopamine & addiction
PET imaging
Opioids
Drug laws and outcomes
Treatment options
Vm PFC – risk, inhibition of impulsivity, emotional decision making; OFC –
reward, social decision making; DLPFC - executive functions, i.e. working
memory, planning, inhibition, abstract reasoning
Background:
Animal studies
• Microdialysis in rats - drugs
abused by humans, including
ethanol, induce DA release in
dorsal caudate and N. accumbens(
DiChiara, 1988)
• Alcohol-preferring rats show
reduced ventral striatal D2/3
receptor density , lower
extracellular DA levels , and
greater VST DA release in
response to alcohol
• increases in DA induced by
drugs are 3-5 fold higher in Nac
than by natural reinforcers (quick
onset of large magnitude).
Dopaminergic pathways
Dopaminergic pathways
Striatal Dopaminergic Synapse
D2
20 studies
Release
3 amphet/2 AMPT
studies
Synthesis
7 FDOPA studies
Glutamate D2
DAT
+
-
Tryptophan
+
D1
DA
DOPA
Tyrosine
D2
DAT
D2
Tyrosine
DOPAdecarboxylase Hydroxylase
Overview
•
•
•
•
•
Dopamine & addiction
PET imaging
Opioids
Drug laws and outcomes
Treatment options
PET Neuroreceptor Imaging
Cyclotron
Radiotracer
PET scanning
11C
BP
Input function
Modeling Analysis
MRI / PET Registration
Slifstein, 2006
Imaging Intrasynaptic Dopamine Release
Baseline
Amphetamine
Challenge
[11C]Raclopride
Dopamine
Abi-Dargham, 2008
PET imaging in addiction research
Volkow et al., 2003
Average [11C]ABP688 BPND (calculated per voxel) images in the healthy
volunteers (top row) and cocaine abusing subjects (second row) for each group.
These images illustrate that cocaine abuse is associated with a decrease in
[11C]ABP688 BPND compared to healthy volunteers.
Martinez et al., Biological Psych, 2013
DA release is decreased in cocaine
dependence
Martinez et al., AJP 2007, 164: 622-629
Background
Chronic stage:
 Martinez et al, 2005, Biol Psych.: Alcoholics also had
lower D2 receptor binding at baseline than controls
 Volkow, J Neurosci. 2007: 20 controls and 20 detoxified
alcoholics, VST and Putamen, 70 and 50% lower than
controls, respectively
Early Stage: vulnerability
 Volkow et al, 2005, Archives of Gen Psych: high levels of
D2 in unaffected family members protect against drinking
 Munro & Wand, 2006, Alcoholism: no difference in
baseline binding or DA release post-amphetamine healthy
subjects with positive family history vs. negative
[11C]raclopride displacement (∆BPND)
Dopamine release in alcoholism
*
Healthy Control
Alcohol Dependent
HC
AD
p
VST
-14.2 ± 8.3%
-5.2% ± 3.6%
0.001*
AST
-8.1% ± 5.5%
-4.6% ± 5.8%
0.10
SMST
-15.3% ± 8.4%
-12.3% ± 7.3%
0.31
Martinez et al., 2004, 2006
Alcohol dependence: Cortical DA release
Narendran et al, Am J Psych, 2014
Dysruption in dopaminergic pathways through
enhanced value of drug leads to addiction
Volkow et al, 2003
Enhanced value of the drug in the reward, motivation, and memory circuits
overcomes inhibitory control of the prefrontal cortex, favoring a positive-feedback
loop initiated by the consumption of the drug and perpetuated by the enhanced
activation of the motivation/drive and memory circuits.
Overview
•
•
•
•
•
Dopamine & addiction
PET imaging
Opioids
Drug laws and outcomes
Treatment options
Opiate receptor & dopamine
Past year initiates for specific illicit drugs among persons aged 12 or older:
2010. Source: Substance Abuse and Mental Health Services Administration.
Results from the 2010 National Survey on Drug Use and Health:Summary of
National Findings
Nationally, deaths from drug overdose were second only to motor vehicle crashes among leading causes of
unintentional injury death. ER visits related to opioid analgesic abuse increased 117 percent between ‘94 and ’01.
There has been at least a 10-fold increase in the medical use of opioid painkillers since 1995, resulting from a
movement toward more aggressive management of pain – and a 5-fold increase in accidental OD deaths
Overview
•
•
•
•
•
Dopamine & addiction
PET imaging
Opioids
Drug laws and outcomes
Treatment options
Brief history of drug laws, policies and attitudes
• Harrison Narcotic Act (1914) earliest significant Federal attempt
to place strict controls on opioids and other substances
• permitted physicians and dentists to dispense opioids “to a
patient … in the course of professional practice only”
• Treasury interpreted the act as a prohibition on physicians'
prescribing opioids to persons with addictions to maintain their
addictions, as not considered “patients”
• 1919: US Supreme Court upheld Treasury's interpretation,
ending, until well into the 1960s, any legitimate role for the
general medical profession in medication-assisted treatment for
people with drug addictions
Brief history of drug laws, policies and attitudes
• 1920s, increase in crime related to acquisition of illicit opioids in
cities throughout the country.
• 1929, Congress established two new treatment facilities that
detoxified patients with opioid addiction who entered voluntarily,
and they also served as hospitals for prison inmates legally
committed to treatment through a Federal court
• social, medical, psychological, and psychiatric services plus
detoxification & low patient-to-staff ratio (about 2 to 1), but the
atmosphere was described as prisonlike
• Overall deemed failures with 93-97% relapse rate, but research
conducted there provided much of the foundation upon which
modern treatment advances were built
Brief history of drug laws, policies and attitudes
• Civil commitment: legislation enabling those with substance
addiction and those “in imminent danger of becoming addicted”
to be confined in rehabilitation centers without first committed or
convicted of a crime.
• instituted in California and New York in the 1960s to allay fears
about addiction-related crimes against people and property in
the inner cities, but minimal results and expensive
• Court decisions after the 1960s generally have required that an
individual be a danger to himself or herself or others before the
legal system can use involuntary commitment
• Controlled Substances Act (1970)
Brief history of drug laws, policies and attitudes
• Drug courts: if charged with a non-violent drug or alcohol related
crime, avoid prison by agreeing to get addiction treatment
instead.
• 1st or 2nd offense, no history of violence or sexual assault
• arrested on a drugs crime, intoxicated or high at the time or
addiction to drugs or alcohol contributed to crime.
• willing and able to comply with any mandated treatment
• willing to plead guilty to crime (in many states, after successfully
completing court mandated treatment criminal record is
expunged)
Brief history of drug laws, policies and attitudes
• A sentence length of between 1 and 2 years
• Mandatory treatment participation
• No drug or alcohol use
• Frequent random drug and alcohol testing
• Frequent court appearances for progress updates
• Making restitution to victims (if any) by community service or
payment
• Rewards for program compliance and sanctions for infractions,
like failed drug tests (e.g. weekend in jai)
Brief history of drug laws, policies and attitudes
• A sentence length of between 1 and 2 years
• Mandatory treatment participation
• No drug or alcohol use
• Frequent random drug and alcohol testing
• Frequent court appearances for progress updates
• Making restitution to victims (if any) by community service or
payment
• Rewards for program compliance and sanctions for infractions,
like failed drug tests (e.g. weekend in jai)
U.S. Prison Population As Of Jan. 25, 2014
e – drug related offenses
Drugs and prison
population
• Between 2001 and 2013, 51% of prisoners serving sentences
of more than a year in federal facilities and 25% in state
facilities were convicted of drug offenses
• 25% among women, 15% among male prisoners
• Only 15% of inmates receive addiction treatment, still prisons
are biggest provider
• As the number of people convicted of drug offenses has gone
up, the federal prison population has increased -- almost 790%
since 1980 leading to overcrowding and endangerment of
inmates and COs
• Mandatory prison sentence for certain drug charges: 5, 10, 20
yrs
• Still: every 4 minutes someone is sent to drug treatment instead
of prison & mandated treatment is as effective as voluntary
ISCD 2010
Overview
•
•
•
•
•
Dopamine & addiction
PET imaging
Opioids
Drug laws and outcomes
Treatment options
“If we as psychiatrists can embrace addiction as a
disease of the brain that disrupts the systems that allow
people to exert self-control, we can reduce the stigma
that surrounds this disorder—for insurance companies
and the wider public—and help to eliminate the shame
and suffering that accompany the addict who
experiences relapse after relapse after relapse.”
-Nora Volkow, APA 2015
Drug-treatment in the US
• US addiction treatment industry had revenues of $34 billion by
2014, an increase of 55% from 2005.
• 80% public funding, ACA will help access
• 14,500 addiction-treatment centers, but only 10% of people 12
yrs or older in need of treatment received it (2.4 mio of 23 Mio)
• Methadone maintenance treatment developed in NYC inmid1960s:Dr. Vincent P. Dole, at Rockefeller University & chair of
Narcotics Committee of the Health Research Council
• & Dr. Marie E. Nyswander, psychiatrist with experience in
treating opioid addiction
• Buprenorphine : UK 1971
• Suboxone: US 2002, EU 2006
Mechanism of action of Suboxone
Treatment seeking cocaine abusers showed that both [11C]raclopride D2 receptor
binding (BPND) and presynaptic dopamine release (BPND) were higher in subjects who
responded to treatment versus those who did not. PET scans (A) from the treatment
responders (top) and nonresponders (bottom) are shown.
DA release by age of onset
*
*: p = 0.04 when compared to age matched controls, AST: 0.07
Experimental treatments for Cocaine
dependence
• Long-acting dextro-amphetamine (e.g. Adderall) – reduces
craving and cocaine, methamphetamine use = agonist
substitution therapy
• Experimental: Vaccinations; repetitive Transcranial Magnetic
Stimulation (rTMS)
Treatments for Alcohol dependence
• Disulfiram (Antabus) – negative reinforcement through aversive
learning
• Naltrexone (Vivitrol) – mu opioid antagonist; reduces craving
through blocked reinforcement
• Acamprosate (Campral) – reduces craving, likely by
antagonizing glu NMDA receptors & agonist at GABA-A
receptors
• Experimental: e.g. Carbamazepine, baclofen, angiotensin
conversion inhibitors, rTMS
Experimental treatments for Cannabis
dependence
• Lithium – reduces symptoms of withdrawal
•
•
•
•
Dronabinol – agonist substitution therapy
Entacapone – COMT inhibitor; decreases craving
N-Acetylcysteine – normalized Glu release; decreases craving
Buspirone - 5HT1A anxiolytic; reduced use
• Naltrexone – reduces craving and use
• rTMS – reduces craving, normalizes prefrontal brain function
Conclusions
•
Addiction has to be considered a medical and mental illness
with profound long-term central and peripheral
neurophysiological changes leading to profound involuntary
behavioral changes and to relapse without adequate treatment
•
There are still limited effective/medical treatment options and
further research is a public health need; a combination of
psychosocial and medical interventions is most effective
•
However, even these options are not available to everyone in
need: costs, un-cooperative & outdated treatment philosophies,
lack of specialized providers & facilites
•
A large portion of patients in need for treatment are
incarcerated instead, most frequently for less harmful drugs