Transcript BrainPowerPointHealy

Daniel Healy, M.D.
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Psychotic Disorders
 Schizophrenia
 Schizoaffective Disorder
Mood Disorders
 Major Depressive Disorder + psychosis
 Bipolar Disorder (Manic-Depression) + psychosis
Anxiety Disorders
 PTSD
 OCD
 GAD
 Panic Disorder
Personality Disorders
 Cluster A (Paranoid, Schizoid, Schizotypal
 Cluster B (Borderline, Antisocial, Narcissiistic, Histrionic)
 Cluster C (Avoidant, Dependent, Obsessive –Compulsive)
Substance Abuse Disorders
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Problem in certain brain regions that comprise circuits
 Frontal lobe- cognition, alertness, control impulses,
motivation
 Temporal lobe (hippocampus plus)-forming memories,
auditory hallucinations
 Thalamus-interprets inputs from the five senses
 Cingulate gyrus-normal expression of emotions
 Caudate-putamen, nucleus accumbens-fine tunes emotions
and movements, reward/reinforcement
 Parietal lobe-allows you to be aware of your own actions
 Amygdala-anxiety, anger
 Hypothalamus-sleeping, eating
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Problem with certain neurotransmitters (nerves don’t
connect, gap is called synapse, neurotransmitters “connect” nerves)
 Dopamine-reward/reinforcement, paranoia, substance abuse
 Glutamate-ubiquitous, excitatory, too much kills neurons,
stress increases cortisol increases glutamate (stress kills
nerves), cognition, pain/temperature, affects dopamine
release
 Serotonin-depression, anxiety, abnormal movements
 GABA-ubiquitous, inhibitory, anxiety, cognition
 Acetylcholine-memory, cognition, movements, nicotine
affects acetylcholine nerves
 http://www.brainexplorer.org is a good website; so is
www.sharpbrains.com, which puts brain function in the
context of investing.
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Why it is complicated
 Billions of connections
 Different brain areas use different neurotransmitters
 Neurotransmitters have multiple types of receptors, some
having opposite effects for same neurotransmitter
 Few medications affect only one neurotransmitter, so can’t
control the (side) effects of medications (most selective, least
effective)
 Homeostasis, tendency to maintain status quo, means that it
is hard to drive one area only
 Giving a medication to affect one area causes changes in other
regions
 Genes and environment are both influential
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Defined by impaired reality testing
Positive symptoms (presence of abnormality):
 thought content: delusions
 perception: hallucinations
 thought stream: grossly disorganized
 behavior: grossly disorganized
Dopamine imbalance in the frontal lobe
and caudate putamen)
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Negative symptoms (absence of normality):
 Affect blunted or flat
 Avolition/amotivation
 Alogia: decreased amount or content
 Anhedonia: lack of interests
Dopamine and glutamate imbalance (too
little frontal lobe, too much in caudate
putamen, maybe amygdala and
hippocampus)
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Stimulus flooding
 Lack of an effective filter
 Too much information from the environment
 Leads to withdrawal from social contact
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Stimulus overload
 Leads to frustration, poor concentration,
nervousness
Thalamus uses gaba and glutamate to filter info
from all five senses
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Chlorpromazine
Fluphenazine
Haloperidol
Loxapine
Mesoridazine
Molindone
Perphenazine
Pimozide
Thioridazine
Thiothixene
Trifluoperazine
Thorazine
Prolixin
Haldol
Loxitane
Serentil
Moban
Trilafon
Orap
Mellaril
Navane
Stelazine
Haloperidol Decanoate (Haldol)
 Fluphenazine Decanoate (Prolixin)
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Effective control of psychotic symptoms in
responsive patients
Reduced need for institutional care
Clinical experience
Relatively inexpensive, generics available
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Lack of efficacy
 Negative symptoms (frontal lobe, glutamate)
 Depression
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Safety and tolerability concerns
 Extrapyramidal symptoms / tardive dyskinesia
(dopamine/acetylcholine in caudate putamen)
 Sedation (frontal lobe)
 Cognitive impairments (frontal lobe)
 Prolactin elevation (dopamine pituitary)
 Cardiovascular symptoms (arrhythmias)
 Nonadherence
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clozapine
risperidone
olanzapine
quetiapine
ziprasidone
aripiprazole
paliperidone
ileoperidone
asenapine
lurasidone
(Clozaril)
(Risperdal)
(Zyprexa)
(Seroquel)
(Geodon)
(Abilify)
(Invega)
(Fanapt)
(Saphris)
(Latuda)
1990
1994
1996
1997
2001
2002
2006
2009
2009
2011
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clozapine (Fazaclo)
risperidone (Risperdal M-tabs)
olanzapine (Zyprexa Zydis)
aripiprazole (Abilify Discmelt)
asenapine (Saphris is sublingual)
risperidone Consta (Risperdal)
 paliperidone Sustenna (Invega)
 olanzapine Relprevv (Zyprexa) (Watch out for
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coma. Seriously.)
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At least as effective as conventional agents
Shift the risk / benefit ratio
The EPS advantage (serotonin)
Reduced risk of tardive dyskinesia (dopamine
serotonin)
Broader symptom efficacy
May enhance compliance, reduce
hospitalizations, be cost-effective
Challenge providers to deliver effective
rehabilitation services
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Expensive
Weight gain, diabetes, cholesterol
Sedating (histamine)
Sometimes not efficacious against positive
symptoms (dopamine)
Seroquel can be a drug of abuse
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Life expectancy increasing in general population
(when controlling for infant mortality)
Life expectancy still around 55 for folks
diagnosed with schizophrenia
Lifestyle improvements not adopted by the
people we serve (exercise, nutrition, smoking)
Access to healthcare
Weight gain from medications
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Sad, irritable or empty mood
Diurnal variation
Diminished capacity for enjoyment
Diminished interests
Frontal lobe, serotonin, norepinephrine,
dopamine (anhedonia)
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Difficulty concentrating
Indecisiveness
Memory problems
Depressed content of thought
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Worthlessness
Guilt
Hopelessness
Death and Suicide
Frontal lobe, serotonin, norepinephrine
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Sleep disturbances
Appetite disturbances, weight changes
Fatigue, low energy
Upset stomach, constipation
Physical pain
Hypothalamus serotonin, norepinephrine,
histamine (sleep)
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Mild to severe
 May include psychosis, poor self care, suicide
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Abraham Lincoln describing his own
depression:
 “I am now the most miserable man living. If
what I feel were equally distributed to the whole
human family, there would not be one cheerful
face on earth. Whether I shall ever be better, I
cannot tell. I awfully forebode I shall not. To
remain as I am is impossible. I must die or be
better, it appears to me.”
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All antidepressants must be taken for at least
4-6 weeks to have substantial benefit
Studies are showing that if you don’t respond
in the first week or two, you’re probably not
going to, so augment or change earlier than
previously recommended.
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Problem in certain brain regions that comprise circuits
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Frontal lobe- mood, cognition, alertness, motivation
Cingulate gyrus-normal expression of emotions
Caudate-putamen-fine tunes emotions and movements
Amygdala-anxiety, anger
Hypothalamus-sleeping, eating
Hippocampus-memory
 Dopamine-reward/reinforcement, anhedonia
 Glutamate-ubiquitous, excitatory, too much kills neurons,
stress increases cortisol increases glutamate (stress kills
nerves), cognition, affects dopamine release
 Serotonin- all aspects of depression
 Norepinephrine- all aspects of depression
 GABA-ubiquitous, inhibitory, anxiety, cognition
 Acetylcholine-memory, cognition,
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Fluoxetine (Prozac)
Sertraline (Zoloft)
Paroxetine (Paxil)
Citalopram (Celexa)
Escitalopram (Lexapro)
Fluvoxamine (Luvox)
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Nausea
Dry mouth
Diarrhea or stomach upset
Lack of appetite
Feeling tired, weak, or dizzy
Headache
Anxiety or nervousness
Sexual dysfunction
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Bupropion (Wellbutrin, Zyban)
 Can cause agitation, anxiety, insomnia
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Venlafaxine (Effexor, Pristiq)
 Hypertension, SSRI-like side effects
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Trazodone (Desyrel)
 Sedation, dizziness
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Nefazodone (Serzone)
 SSRI-like but more sedation, monitor for liver toxicity
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Mirtazapine (Remeron)
 May cause sedation, weight gain
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Duloxetine (Cymbalta)
 May cause nausea
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Amitriptyline (Elavil)
Clomipramine (Anafranil)
Desipramine (Norpramin)
Doxepin (Sinequan)
Imipramine (Tofranil)
Nortriptyline (Pamelor)
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Can be fatal in overdose
Fatigue, sedation
Light-headedness, dizziness
Dry mouth
Constipation
Weight gain
Headache
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Isocarboxazid (Marplan)
Meclobemide (Aurorix)
Phenelzine (Nardil)
Tranylcypromine (Parnate)
Selegiline (Eldepryl)
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Strict dietary restriction
 Avoid aged cheeses and meats, soy sauce, soy
beans, fava beans, wine, beer, others
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Avoid other anti-depressants
Avoid over-the-counter medications
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Hypertensive crisis
Serotonin syndrome
Weight gain
Fatigue
Constipation
Dizziness
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1% of general population
Equal in men and women
Age of onset similar to schizophrenia
Episodes can come on very fast (1-7 days)
Later episodes longer, more severe, more frequent
Substance abuse common
Heredity plays a greater role than in depression
Family members also at higher risk for major
depression
High suicide risk
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Persistently elevated, expansive or irritable mood for
one week
Associated symptoms (need 3 or more for diagnosis)
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Inflated self -esteem or grandiosity
Decreased need for sleep
More talkative
Racing thoughts or flight of ideas
Distractibility
Agitation or increase in activities
Excessive involvement in pleasurable activities with a high risk for
painful consequences
 Spending sprees, sexual indiscretions, foolish investments
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Distinct period of persistently elevated, expansive, or irritable mood, lasting
throughout at least 4 days plus three of the following:
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inflated self-esteem or grandiosity
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decreased need for sleep (e.g., feels rested after only 3 hours of sleep)
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more talkative than usual or pressure to keep talking
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flight of ideas or subjective experience that thoughts are racing
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distractibility (i.e., attention too easily drawn to unimportant or irrelevant
external stimuli)
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increase in goal-directed activity (either socially, at work or school, or sexually)
or psychomotor agitation
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excessive involvement in pleasurable activities that have a high potential for
painful consequences (e.g., engaging in unrestrained buying sprees, sexual
indiscretions, or foolish business investments)
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The criteria are met both for a Manic Episode and for a Major Depressive
Episode (except for duration) nearly every day during at least a 1-week period.
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B. The mood disturbance is sufficiently severe to cause marked impairment in
occupational functioning or in usual social activities or relationships with
others, or to necessitate hospitalization to prevent harm to self or others, or
there are psychotic features.
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C. The symptoms are not due to the direct physiological effects of a substance
(e.g., a drug of abuse, a medication, or other treatment) or a general medical
condition (e.g., hyperthyroidism).
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Frontal lobe and amygdala-emotion regulation
Impulsivity-dopamine reward/reinforcement
Lack of need for sleep-histamine
Increased neuronal firing, glutamate
Mood stabilizers may reduce the chemicals
produced after a nerve fires
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FDA Approved Agents
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lithium (Eskalith, Lithobid) (mania, depression)
valproate (Depakote) (mania)
carbamazepine XR (Tegretol XR) (mania)
aripiprazole (Abilify) (mania)
asenapine (Saphris) (mania)
chlorpromazine (Thorazine) (mania)
olanzapine (Zyprexa) (mania)
olanzapine + fluoxetine (depression)
lamotrigine (Lamictal) (depression prevention)
risperidone (Risperdal) (mania)
quetiapine (Seroquel) (depression, mania)
ziprasidone (Geodon) (mania)
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Toxic in overdose
 Severe tremor, confusion, disorientation, seizure,
coma
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Can check blood levels
Tremor
Gastrointestinal symptoms
Increased weight
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Monitor blood levels
Stomach upset
Weight gain
Sedation
Liver failure
 Yellowing of skin or eyes, dark urine, nausea/vomiting
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Pancreatitis
 Abdominal pain, nausea/vomiting, decreased appetite
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Polycystic Ovary risk
Hair loss
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Other anticonvulsants
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Oxcarbazepine (Trileptal)
Topiramate (Topamax)
Tiagabine (Gabitril)
Gabapentin (Neurontin)
Other second generation antipsychotics
 iloperidone (Fanapt)
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Conventional neuroleptics
Benzodiazapines
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Posttraumatic Stress Disorder
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Obsessive Compulsive Disorder
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Generalized Anxiety Disorder
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Panic Disorder with or without
agoraphobia
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SSRIs, SNRIs, TCAs effective in concert
with psychotherapy
Amygdala mediates fear and anxiety,
GABA+glutamate balance,
norepinephrine, dopamine, serotonin
Frontal lobe mediates increased
attention/vigilance, norepinephrine
Hypothalamus-blood pressure, increased
heart rate
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Fluoxetine (Prozac)
Sertraline (Zoloft)
Paroxetine (Paxil)
Citalopram (Celexa)
Escitalopram (Lexapro)
Fluvoxamine (Luvox)
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Bupropion (Wellbutrin, Zyban)
 Can cause agitation, anxiety, insomnia
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Venlafaxine (Effexor, Pristiq)
 Hypertension, SSRI-like side effects
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Trazodone (Desyrel)
 Sedation, dizziness
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Nefazodone (Serzone)
 SSRI-like but more sedation, monitor for liver toxicity
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Mirtazapine (Remeron)
 May cause sedation, weight gain
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Duloxetine (Cymbalta)
 May cause nausea
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Alprazolam (Xanax)
Chlordiazepoxide (Librium)
Clonazepam (Klonopin)
Diazepam (Valium)
Lorazepam (Ativan)
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Oxazepam (Serax)
Temazepam (Restoril)
Triazolam (Halcion)
Zolpidem (Ambien)
Zaleplon (Sonata)
Note: all have addiction potential, last four mostly for sleep,
GABA in amygdala a major target
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Sedation
Addiction potential
Can be fatal in overdose, especially if
combined with alcohol
Studies show most likely outcome for adding a
benzo is to create benzo dependence; either
no benefit or trigger for abusing other
substances
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Severe craving lengthens tapering off period
Taking benzos decreases craving for benzos,
alcohol, or other substance of abuse, but does
not improve illness
Folks with bipolar disorder and depression
have a very high risk of developing benzo
abuse/dependence, with no evidence that
benzos beneficial for mood
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Many states are restricting or eliminating
benzos from formulary
Time-limited, supervised use for
detox/withdrawal and akasthisia now only
acceptable use for benzos
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Intending to use the substance
Hoping not to get in trouble
Make bad choices
Do get in trouble
Outcome goal- abstinence or non-harmful use
Dopamine in nucleus accumbens, amygdala
frontal lobe, temporal lobe (withdrawal
balance of GABA and glutamate)
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Achieve abstinence before treating
mood, anxiety or psychotic disorder
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Psychotropic medications reduced the
likelihood of sobriety
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No medications available to facilitate
sobriety (Antabuse-no data on sobriety)
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Treat all illnesses simultaneously, and
combine medications designed to
enhance sobriety with psychosocial
interventions
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Harm reduction is a useful treatment
goal as part of the treatment plan.
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Comorbidity is the expectation, not the
exception
 Persons diagnosed with schizophrenia
 47% use substances
 55% of those in psychiatric treatment
 Bipolar disorder
 62% have substance use disorder
 Bipolar consumers more likely to abuse alcohol and cannabis
than MDD
 Major Depressive disorder
 More likely to have alcohol dependence than abuse
 Consumers with mood disorders, in general, are likely to
abuse benzodiazepines.
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Provision for basic needs
Assertive community treatment (ACT)
Patient and family psychoeducation
Vocational rehabilitation
Clubhouses
Social skills training
Support groups
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Motivational enhancement therapy
Cognitive behavioral (relapse prevention)
12 step programs
Contingency management
Family interventions
Self-help manuals/workbooks
Case management
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There is little evidence that there is a gene that
increases likelihood that you will have a cooccurring disorder
There is also little evidence that any one factor
“causes” you to develop co-occurring disorder
(e.g. personality disorder, “addictive
personality”).
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There is little agreement whether mood disorder
symptoms precede or follow substance abuse
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NO (most of the time)
Treat both conditions simultaneously
Yearly schizophrenia relapse rate
 With medication - 15-20%
 Without medication - 70%
 Without medication and with precipitant such as
substance abuse – greater than 70%
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With deinstitutionalization, more choices including selfdetermination
Not just to self-medicate symptoms
Relieves feelings of isolation, loneliness, boredom and
despair
Facilitates peer interaction and social engagement
Promotes a sense of well-being, escape from life perceived
as bleak or hopeless, mitigates withdrawal
Harder to modify behavior if have cognitive impairments
Increases metabolism, effectively reducing doses of
medications
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disulfiram (Antabuse)
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Works by interfering with alcohol metabolismcousin of formaldehyde accumulates in blood,
causing illness
Doesn’t affect craving directly, limited data on
relapse reduction
More of an aversive treatment
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Avoid alcohol in any form (aftershave, etc)
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naltrexone (Revia)
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Works by affecting endogenous opioid system
Reduces craving
Will induce withdrawal if consumer using or
abusing opiates
Can’t use opiates for pain management
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injectible naltrexone (Vivitrol)
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Works by affecting endogenous opioid system
Reduces craving
Will induce withdrawal if consumer using or
abusing opiates
Can’t use opiates for pain management
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acamprosate (Campral)
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Works by affecting glutamate and/or GABA
receptors
May reduce craving by mitigating early
withdrawal, and reduces relapse rates
Avoid if consumer has kidney problems
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methadone (Dolophine)
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Works by occupying opiate receptors in same
way morphine and its cousins do
Will reduce withdrawal symptoms but some
abuse potential
Needs to be prescribed in a subspecialty clinic
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buprenorphine (Suboxone)
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Works by occupying opiate receptors without
fully stimulating them
Will reduce withdrawal symptoms and may
have less abuse potential than methadone
Prescribers must go through special training in
order to prescribe
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imipramine (Tofranil)
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Used to treat depression in consumer with
opiate abuse/dependence
Treatment for depression with imipramine was
associated with reduced craving for, and selfreported use of, opiates, cocaine, and cannabis
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Nicotine replacement
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Works same way smoking and dipping does
May reduce craving by occupying and
stimulating receptors
Available in multiple delivery systems
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buproprion (Zyban, Wellbutrin)
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Works through the dopamine and
norepinephrine system (presumably)
May reduce craving indirectly
Effect independent of antidepressant effect
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Varenicline (Chantix)
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Works by occupying nicotinic receptors,
blocking nicotine effects
May reduce craving by mildly stimulating
receptors
Nicotinic receptors are odd: initially
stimulated, then shut down
Insomnia, agitation, psychosis possible
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No medication approved for caffeine
use/abuse
Caffeine blocks adenosine
Adenosine receptors in brain affect
wakefulness
Adenosine receptors in the heart regulate
rhythm
Adenosine receptors in stomach affect acid
secretion
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Consumers on clozapine seem to have lower
rates of substance abuse
Lithium for adolescents seems to reduce
alcohol abuse
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Withdrawal from alcohol and benzos can be
fatal
Withdrawal from opiates is very
uncomfortable, with significant physical
symptoms, but rarely fatal
Withdrawal from cocaine rarely requires close
supervision
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Accessible
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Flexible
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Capable
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Individualized
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Comprehensive
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Willing and Tolerant
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Continuous
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Culturally competent
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Integrated
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Safe housing
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Meaningful daytime activity
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Sober support network
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Positive alliance with at least one treatment
provider
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Social work interventions reduce stress,
preserving brain function, and leading to
better outcomes
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Can’t remember
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Don’t have an illness, so
don’t need medications
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Difficult medication
schedule
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Stigma of taking a
psychiatric medication
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Don’t like/trust the
prescriber
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The meds aren’t
working
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Fear of medications
Bad side effects
No social support
Conditions that may be related to problems with brain
regions that mediate facial recognition
Capgras-delusion that family and friends are imposters
Fregoli-delusion that one person is wearing many disguises, so multiple people are
actually just one person
Cotard-delusion that all of organs are gone or they are dead
Autism and Aspergers-interpersonal difficulties may be related to inability to recognize
facial expressions
Depersonalization-delusion that the face in the mirror is not you
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Denial-you understand, on some level, your actions
and consequences, but this understanding does not
influence behavior
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Anosognosia or lack of insight is the physical
inability to understand your actions while sick
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Anosognosia is more similar to amnesia than to
denial
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Coercion assumes that the role of the treatment team is to be right and to
minimize risk liabilities
Therefore, take the steps necessary to optimize a narrowly defined outcome
(e.g. suicide prevention)
Hospitalization and symptom improvement most likely interventions when
suicide risk acutely increased
Both are independent risk factors for completed suicide, so…what are we
doing?
Recovery is a civil rights movement similar to the advances made by the
physically disabled to (re-)integrate into the community
Society created accommodations for physically disabled (ramps, automatic
doors, etc) so they could participate in society
Accommodations for the mentally ill were not included in this movement,
necessitating a separate movement
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Basic tenets of the recovery movement include hope, engagement,
supporting self-efficacy, and the dignity of risk
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Treatment providers should take a consultative, rather than directive, role in
the treatment of psychiatric illnesses; fewer appointments, and more walkin availability
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Note that recovery is not a synonym for symptom remission; consumers can
be symptomatic and still participate in society
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The role of any health care intervention is to shift the odds in your favor;
ownership of outcomes cannot rest solely on health care providers
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Psychiatric illness associated with increased mortality (life expectancy in
your 50s), even when suicide excluded; so…what are we doing?
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Some have argued that coercive treatment is an accommodation for asognosia (lack
of insight into need for treatment)
Others have argued that coercive treatment is a legitimate engagement tool, but
should not be relied upon for prolonged periods of time
Still others argue that ATOs and recovery can never be reconciled, and they are even
against involuntary hospitalization
Intensive outreach and engagement are the keys to recovery; court orders merely
obligate staff to do the job they should be doing anyway (and without resorting to
restrictions of liberty)
Do ATO’s reduce or increase autonomy?
 Treatment Advocacy Center: “Severe mental illness, not its treatment, restricts
civil liberties. By assuring timely and effective intervention for the disabling
medical condition of severe mental illness, assisted outpatient treatment restores
the capacity to exercise civil liberties and reduces the likelihood of the loss of
liberty or life as a result of arrest, incarceration, hospitalization, victimization,
suicide and other common outcomes of non-treatment.”
Thanks for your time
Thanks for your time!
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Shout out to Dr Tom Coles, for finishing the
Detroit Free Press/Talmer Bank Marathon and
raising awareness for the Brain & Behavior
Research Foundation (formerly NARSAD)