Ethical implications of mental health care and institutionalization

1. Ethical implications of mental health care and institutionalization Nina B. Urban, MD, MSc, FAPAAssistant Professor of PsychiatryColumbia UniversityDivision of Substance AbuseGlobal Bioethics Summer School, NYCJuly 2, 2015

2. Disclosures • No conflicts of interest to report

3. Overview • Dopamine & addiction • PET imaging • Opioids • Drug laws and outcomes • Treatment options

4. Overview • Dopamine & addiction • PET imaging • Opioids • Drug laws and outcomes • Treatment options

5. 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

6. 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).

7. Dopaminergic pathways

8. Dopaminergic pathways

9. Striatal Dopaminergic Synapse D2 20 studies Release 3 amphet/2 AMPT studies Glutamatergic Neuron Synthesis 7 FDOPA studies Glutamate - D2 NMDA DAT Tryptophan + + - D1 DOPA DA Tyrosine D2 TyrosineHydroxylase DOPA-decarboxylase DAT D2 Dopaminergic Neuron GABAergic Neuron

12. Overview • Dopamine & addiction • PET imaging • Opioids • Drug laws and outcomes • Treatment options

13. PET Neuroreceptor Imaging Cyclotron Radiotracer PET scanning 11C BP Input function Modeling Analysis MRI / PET Registration Slifstein, 2006

14. [11C]Raclopride Dopamine Imaging Intrasynaptic Dopamine Release AmphetamineChallenge Baseline Abi-Dargham, 2008

15. PET imaging in addiction research Volkow et al., 2003

16. 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

17. DA release is decreased in cocaine dependence Martinez et al., AJP 2007, 164: 622-629

18. 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

19. Healthy Control Alcohol Dependent Dopamine release in alcoholism * [11C]raclopride displacement (∆BPND) Martinez et al., 2004, 2006

20. Alcohol dependence: Cortical DA release Narendran et al, Am J Psych, 2014

21. 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.

22. Overview • Dopamine & addiction • PET imaging • Opioids • Drug laws and outcomes • Treatment options

23. Opiate receptor & dopamine

25. 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

26. 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

27. Overview • Dopamine & addiction • PET imaging • Opioids • Drug laws and outcomes • Treatment options

28. 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

29. 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

30. 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)

31. 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)

32. 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)

33. 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)

34. U.S. Prison Population As Of Jan. 25, 2014 e – drug related offenses

36. 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

38. ISCD 2010

39. Overview • Dopamine & addiction • PET imaging • Opioids • Drug laws and outcomes • Treatment options

41. “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

42. 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 inmid-1960s: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

43. Mechanism of action of Suboxone

44. 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.

45. DA release by age of onset * *: p = 0.04 when compared to age matched controls, AST: 0.07

46. 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)

47. 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

48. 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

49. 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