Brain diseases: Substance abuse and cooccurring disorders

1
Brain diseases Substance abuse and co-occurring
disorders

• Mark Publicker, MD FASAM
• Medical Director
• Mercy Recovery Center

2
Questions

• Does mental illness cause substance abuse?
• Does substance abuse cause mental illness?
• Are there differences in populations identified
  as primarily psychiatric or as substance abusers?

3
Addiction

• A chronic but treatable brain disease
  characterized by
• loss of control
• compulsive use
• use despite known harm
• relapse

4
Comorbid substance abuse

• Common problem in psychiatric patients
• Contributes to treatment refractoriness,
  non-compliance and increased health services
  utilization and cost

5
Rand Survey of Care, 2001

• 3 US population has co-occuring disorders
• Of these
• 72 received no treatment in previous 12 months
• Only 8 received both mental and substance abuse
  treatment
• Only 23 of those in treatment received
  appropriate treatment

6
Current situation in treatment systems

• Comorbid rates are high
• Patients are most costly to treatment and less
  responsive to treatment
• Different services are provided according to
  entry portal
• Managed care expectations unrealistic

7
Co-morbid psychiatric disorders

• Depression
• Anxiety disorders
• Bipolar disorder

• Schizophrenia
• ADHD
• PTSD
• ASP
• Axis II disorders

8
Epidemiology

• 50 lifetime prevalence of substance abuse
  disorders for psychiatric patients
• Schizophrenia prevalence rates of 70 in some
  surverys
• Onset of symptoms earlier in drug-abusing
  schizophrenics

9
Epidemiology

• Schizophrenia substance abuse associated with
  higher rates of homelessness, non-compliance,
  medical illness and violence
• Bipolar disorder rates estimated to be 50-70
• Associated with worse prognosis

10
Epidemiology

• Unipolar depression 30-50
• Associated with treatment resistance and greater
  severity
• Worsens alcohol dependence treatment outcomes

11
Epidemiology

• ADHD NIDA estimates up to 50 of substance
  abuse patients
• Increased risk of SUD up to 9 times
• Effective childhood treatment reduces risk

12
Epidemiology

• PTSD increased risk of SUD
• Hypothalamic and noradrenergic mechanisms
• PTSD precedes SUD
• Substance abuse modifies neurobiologic substrate,
  intensifying PTSD symptoms which in turn
  intensify SUD

13
PTSD

• In course of use, drug abusers place selves in
  dangerous situations
• Withdrawal symptoms overlap with arousal symptoms
• Increased CRH sensitizes LC, increasing
  noradrenergic tone which increases CRH release
• Increased CRH by both substance abuse and PTSD
  potentiate fear responses in amygdala

14
Epidemiology - Nicotine

• Nicotine-dependent patients with comorbid
  disorders 7.1 US population consume 34.2 of
  all cigarettes smoked

15
Havassy et al. AJP 1/2004

• Comparison study of comorbid patients recruited
  in two treatment settings
• Residential (non-hospital) psychiatric for
  seriously mentally ill patients
• Equivalent Substance abuse residential program

16
Havassy et al.

• Of 420 eligible patients, 54 (N226) met
  comorbid criteria
• More MI patients met comorbid criteria than did
  SA (60-49)

17
Havassy et al

• No significant differences in overall rates of
  mental disorders
• Higher prevalence of schizophrenic spectrum
  disorders in MI setting (43-31)
• No signficant difference in bipolar prevalence

18
Havassy et al

• SA setting decreased likelihood of suicide and
  psychiatric hospitalization history
• No significant differences in rates of substance
  abuse
• Severity of SA higher in SA setting

19
Havassy et al

• SA prevalence
• Less opiate and cocaine use in schizophrenic
  patients
• No difference in days of use
• More similarities than
• differences in two settings

20
Self-medication hypothesis

• Evidence nicotine attenuates stress reactivity
• Schizophrenia use nicotine to deal with negative
  symptoms sleep, dysphoria, antipsychotic adverse
  effects and to improve cognitive function

21
Neurobiology

• Drugs of abuse interact and alter neural
  substrates related to the pathobiology of
  psychiatric disorders
• More neuropsychologic impairment

22
Substance augmentation

• Koob feed-forward system increases stress
  reactivity
• Withdrawal states
• Problem-solution interaction

23
Neurobiology

• Same neurotransmitter systems
• Dopamine
• Serotonin
• GABA
• Glutamate
• Endogenous opioids

24
Definition

• Addiction is a cycle of spiraling dysregulation
  of brain reward systems that progressively
  increases, resulting in compulsive drug use and a
  loss of control over drug taking George Koob

25
Genetics

• No single gene
• 40 genetic
• Cloningers twin study
• COGA

26
(No Transcript)
27
Pathophysiology

• Neural circuitry of reward and brain reward
  thresholds
• Tolerance
• Altered hedonic tone
• Sensitization
• Activation of HPA axis
• Genetic predisposition

28
Neural circuitry of reward

• Present in all animals
• Produces pleasure for behaviors needed for
  survival
• Eating
• Drinking
• Sex
• Nurturing

29
Self-stimulation studies
30
All drugs of abuse bind to the neural circuitry
of reward
31
All drugs abuse increase dopamine in the nucleus
accumbens

• alcohol
• cocaine
• heroin
• marijuana
• nicotine

• amphetamines
• sedatives
• hallucinogens
• pcp
• caffeine

32
Drugs of abuse hijack the Reward Center

• Instead of eating, drinking and making love,
  drugs tell you that you need to take them in
  order to survive.
• This is obviously a lie, and one that leads to
  sickness and death.

33
(No Transcript)
34
Neuroadaptation

• drugs change the brains balance
• the brain has mechanisms to oppose this change
• the balancing action overshoots
• the stronger the drug, the higher the dosage and
  the longer the use, the more the opposing change

35
Neuroadaptation - alcoholics drink

• to get high
• to get sedated
• to get numb

36
Neuroadaptation alcohol

• high depressed
• sedated anxious/sleepless
• numb anguish/pain

37
NeuroadaptationAlcoholics drink

• to get high
• to get sedated
• to get numb

38
Neuroadaptation alcohol

• high depressed
• sedated anxious/sleepless
• numb anguish/pain

39
Positive reinforcers

• Euphoria
• Sedation
• Anesthesia (numbing)

40
Negative reinforcers

• depression
• anxiety
• insomnia
• boredom
• loss of pleasure

41
Cocaine and mood changes
42
Opponent process theory
43
Opponent process - heroin
44
Allostasis

• change to new, vulnerable state
• deficit states inhibition of brain reward
  circuitry
• altered hedonic tone (Koob)
• reward thresholds increase
• opponent process theory
• counteradaptive hedonic dysregulation

45
(No Transcript)
46
Cocaine PET scan
47
SPECT scan healthy brain top down and underside
48
Heroin SPECT scans
49
Alcohol
Intoxication
Sober 30 days
50
Cannabis

• Prospective studies demonstrate increased risk
• Schizophrenia
• Major depressive disorder
• Anxiety disorders, including panic

51
Volkow methamphetamine

• Persistent reductions in dopamine transport in
  striatum
• Long-term psychomotor impairment

52
Methamphetamine
53
Conditioning

• Ivan pavlov
• Conditioned dogs to salivate when they heard a
  bell
• 7-11

54
Amygdala

• Emotional responses
• filters all incoming sensations
• identifies both high risk and high pleasure
  stimuli
• very rapid response

55
Limbic conditioning
56
Brain organization
57
(No Transcript)
58
Brain organization

• The right brain thinks with images, not words
• There is no DONT ELEPHANT in the right brain
• DONT ELEPHANT ELEPHANT!!

59
Which step says Dont drink?

• None of them

60
Medications

• Naltrexone (revia)
• Topiramate
• Acamprosate
• Methadone
• Buprenorphine
• Bupropion

61
Methadone

• Abstinence rates 70-80
• Blocks craving
• Blocks euphoria
• Normalization of HPA axis
• Normalization of limbic function

62
Methadone

• High rates of major depressive disorder and
  anxiety disorders
• Treatment research
• Tricyclic antidepressants, SSRIs and CBT
  effective
• Methadone supports treatment compliance over
  active using condition

63
Buprenorphine/naloxone Suboxone

• Partial agonist pure antagonist
• t/2 gt24 hours
• Blocks craving and euphoria
• Less physical dependence
• Combo decreases diversion risk

64
Suboxone

• DATA 2000 can be prescribed by office-based
  physicians
• DEA waiver
• 30 patient limit
• Adolescent/young adults
• September 2004 training

65
Therapeutic effects

• blocking effect on euphoria with administration
  of heroin
• blocking effect on withdrawal.
• relieves craving
• stabilization of brain function
• decrease in HPA stress state
• improvement in mood and
• behavioral stability

66
Revia - Naltrexone

• Pure opioid antagonist
• Effective in treatment of alcoholism and opiate
  addiction
• Blocks craving
• Blocks the high and increases the negatives

67
Acamprosate - Campral

• NMDA receptor antagonist
• Blocks craving
• Doubles abstinence rates
• Additive with naltrexone

68
Topiramate

• Anti-convulsant
• Anti-craving agent for alcohol, cocaine and
  cannabis
• Increases alcohol abstinence rates by 50
• Patients reports enhanced sense of well-being

69
Zyban (bupropion)

• Antidepressant
• decreases craving
• decreases withdrawal
• can increase abstinence rates
• side effects GI, anxiety, headaches

70
Summary

• Addiction and psychiatric disorders are treatable
  brain diseases
• Research is edifying the biological mechanisms
  involved
• Increased understanding of neurobiology is
  allowing for the development of effective,
  targeted pharmacotherapies