Daniel Healy, M.D.Daniel Healy, M.D.

Psychotic DisordersPsychotic Disorders SchizophreniaSchizophrenia Schizoaffective DisorderSchizoaffective Disorder

Mood DisordersMood Disorders Major Depressive Disorder Major Depressive Disorder ++ psychosis psychosis Bipolar Disorder (Manic-Depression) Bipolar Disorder (Manic-Depression) ++ psychosis psychosis

Anxiety DisordersAnxiety Disorders PTSDPTSD OCDOCD GADGAD Panic DisorderPanic Disorder

Personality DisordersPersonality Disorders Cluster A (Paranoid, Schizoid, SchizotypalCluster A (Paranoid, Schizoid, Schizotypal Cluster B (Borderline, Antisocial, Narcissiistic, Histrionic)Cluster B (Borderline, Antisocial, Narcissiistic, Histrionic) Cluster C (Avoidant, Dependent, Obsessive –Compulsive)Cluster C (Avoidant, Dependent, Obsessive –Compulsive)

Substance Abuse DisordersSubstance Abuse Disorders

Problem in certain brain regions that comprise Problem in certain brain regions that comprise circuitscircuits Frontal lobe- cognition, alertness, control impulses, Frontal lobe- cognition, alertness, control impulses,

motivationmotivation Temporal lobe (hippocampus plus)-forming memories, Temporal lobe (hippocampus plus)-forming memories,

auditory hallucinationsauditory hallucinations Thalamus-interprets inputs from the five sensesThalamus-interprets inputs from the five senses Cingulate gyrus-normal expression of emotionsCingulate gyrus-normal expression of emotions Caudate-putamen, nucleus accumbens-fine tunes Caudate-putamen, nucleus accumbens-fine tunes

emotions and movements, reward/reinforcementemotions and movements, reward/reinforcement Parietal lobe-allows you to be aware of your own Parietal lobe-allows you to be aware of your own

actions actions Amygdala-anxiety, angerAmygdala-anxiety, anger Hypothalamus-sleeping, eatingHypothalamus-sleeping, eating

Problem with certain neurotransmitters Problem with certain neurotransmitters (nerves (nerves don’t connect, gap is called synapse, neurotransmitters “connect” nerves)don’t connect, gap is called synapse, neurotransmitters “connect” nerves)

Dopamine-reward/reinforcement, paranoia, substance abuseDopamine-reward/reinforcement, paranoia, substance abuse Glutamate-ubiquitous, excitatory, too much kills neurons, Glutamate-ubiquitous, excitatory, too much kills neurons,

stress increases cortisol increases glutamate (stress kills stress increases cortisol increases glutamate (stress kills nerves), cognition, pain/temperature, affects dopamine nerves), cognition, pain/temperature, affects dopamine releaserelease

Serotonin-depression, anxiety, abnormal movementsSerotonin-depression, anxiety, abnormal movements GABA-ubiquitous, inhibitory, anxiety, cognitionGABA-ubiquitous, inhibitory, anxiety, cognition Acetylcholine-memory, cognition, movements, nicotine Acetylcholine-memory, cognition, movements, nicotine

affects acetylcholine nervesaffects acetylcholine nerves

http://www.brainexplorer.org is a good website; so is is a good website; so is www.sharpbrains.comwww.sharpbrains.com, which puts brain function in the context of investing.

Why it is complicatedWhy it is complicated Billions of connectionsBillions of connections Different brain areas use different neurotransmittersDifferent brain areas use different neurotransmitters Neurotransmitters have multiple types of receptors, Neurotransmitters have multiple types of receptors,

some having opposite effects for same some having opposite effects for same neurotransmitterneurotransmitter

Few medications affect only one neurotransmitter, so Few medications affect only one neurotransmitter, so can’t control the (side) effects of medications (most can’t control the (side) effects of medications (most selective, least effective)selective, least effective)

Homeostasis, tendency to maintain status quo, means Homeostasis, tendency to maintain status quo, means that it is hard to drive one area onlythat it is hard to drive one area only

Giving a medication to affect one area causes changes Giving a medication to affect one area causes changes in other regionsin other regions

Genes and environment are both influentialGenes and environment are both influential

Defined by impaired reality testingDefined by impaired reality testing Positive symptoms (presence of Positive symptoms (presence of

abnormality):abnormality): thought content: delusionsthought content: delusions perception: hallucinationsperception: hallucinations thought stream: grossly disorganizedthought stream: grossly disorganized behavior: grossly disorganizedbehavior: grossly disorganizedDopamine imbalance in the frontal lobe Dopamine imbalance in the frontal lobe

and caudate putamen)and caudate putamen)

Negative symptoms (absence of normality):Negative symptoms (absence of normality): Affect blunted or flatAffect blunted or flat Avolition/amotivationAvolition/amotivation Alogia: decreased amount or contentAlogia: decreased amount or content Anhedonia: lack of interestsAnhedonia: lack of interestsDopamine and glutamate imbalance (too Dopamine and glutamate imbalance (too

little frontal lobe, too much in caudate little frontal lobe, too much in caudate putamen, maybe amygdala and putamen, maybe amygdala and hippocampus)hippocampus)

Stimulus floodingStimulus flooding Lack of an effective filterLack of an effective filter Too much information from the environmentToo much information from the environment Leads to withdrawal from social contactLeads to withdrawal from social contact

Stimulus overloadStimulus overload Leads to frustration, poor concentration, Leads to frustration, poor concentration,

nervousnessnervousnessThalamus uses gaba and glutamate to filter Thalamus uses gaba and glutamate to filter

info from all five sensesinfo from all five senses

ChlorpromazineChlorpromazineThorazineThorazine FluphenazineFluphenazine ProlixinProlixin HaloperidolHaloperidol HaldolHaldol LoxapineLoxapine LoxitaneLoxitane MesoridazineMesoridazine SerentilSerentil MolindoneMolindone MobanMoban PerphenazinePerphenazine TrilafonTrilafon PimozidePimozide OrapOrap ThioridazineThioridazine MellarilMellaril ThiothixeneThiothixene NavaneNavane TrifluoperazineTrifluoperazine StelazineStelazine

Haloperidol Decanoate Haloperidol Decanoate (Haldol)(Haldol)

Fluphenazine Decanoate Fluphenazine Decanoate (Prolixin)(Prolixin)

Effective control of psychotic Effective control of psychotic symptoms in responsive patientssymptoms in responsive patients

Reduced need for institutional Reduced need for institutional carecare

Clinical experienceClinical experience Relatively inexpensive, generics Relatively inexpensive, generics

availableavailable

Lack of efficacyLack of efficacy Negative symptoms (frontal lobe, glutamate)Negative symptoms (frontal lobe, glutamate) DepressionDepression

Safety and tolerability concernsSafety and tolerability concerns Extrapyramidal symptoms / tardive dyskinesia Extrapyramidal symptoms / tardive dyskinesia

(dopamine/acetylcholine in caudate putamen)(dopamine/acetylcholine in caudate putamen) Sedation (frontal lobe)Sedation (frontal lobe) Cognitive impairments (frontal lobe)Cognitive impairments (frontal lobe) Prolactin elevation (dopamine pituitary)Prolactin elevation (dopamine pituitary) Cardiovascular symptoms (arrhythmias)Cardiovascular symptoms (arrhythmias) NonadherenceNonadherence

clozapine clozapine (Clozaril) (Clozaril) 19901990 risperidone risperidone (Risperdal) (Risperdal) 19941994 olanzapine olanzapine (Zyprexa) (Zyprexa) 19961996 quetiapine quetiapine (Seroquel) (Seroquel) 19971997 ziprasidone ziprasidone (Geodon)(Geodon) 20012001 aripiprazolearipiprazole (Abilify)(Abilify) 20022002 paliperidonepaliperidone (Invega)(Invega) 20062006 ileoperidoneileoperidone (Fanapt)(Fanapt) 20092009 asenapineasenapine (Saphris)(Saphris) 20092009 lurasidone lurasidone (Latuda)(Latuda) 20112011

clozapine (Fazaclo) clozapine (Fazaclo) risperidone (Risperdal M-tabs) risperidone (Risperdal M-tabs) olanzapine (Zyprexa Zydis) olanzapine (Zyprexa Zydis) aripiprazole (Abilify Discmelt)aripiprazole (Abilify Discmelt) asenapine (Saphris is sublingual)asenapine (Saphris is sublingual)

risperidone Consta risperidone Consta (Risperdal)(Risperdal)

paliperidone Sustenna paliperidone Sustenna (Invega)(Invega)

olanzapine Relprevv olanzapine Relprevv (Zyprexa) (Zyprexa) (Watch out for coma. Seriously.)(Watch out for coma. Seriously.)

At least as effective as conventional agentsAt least as effective as conventional agents Shift the risk / benefit ratioShift the risk / benefit ratio The EPS advantage (serotonin)The EPS advantage (serotonin) Reduced risk of tardive dyskinesia (dopamine Reduced risk of tardive dyskinesia (dopamine

serotonin)serotonin) Broader symptom efficacyBroader symptom efficacy May enhance compliance, reduce May enhance compliance, reduce

hospitalizations, be cost-effectivehospitalizations, be cost-effective Challenge providers to deliver effective Challenge providers to deliver effective

rehabilitation servicesrehabilitation services

ExpensiveExpensive Weight gain, diabetes, cholesterol Weight gain, diabetes, cholesterol Sedating (histamine)Sedating (histamine) Sometimes not efficacious against Sometimes not efficacious against

positive symptoms (dopamine)positive symptoms (dopamine) Seroquel can be a drug of abuseSeroquel can be a drug of abuse

Life expectancy increasing in general Life expectancy increasing in general population (when controlling for infant population (when controlling for infant mortality)mortality)

Life expectancy still around 55 for folks Life expectancy still around 55 for folks diagnosed with schizophreniadiagnosed with schizophrenia

Lifestyle improvements not adopted by the Lifestyle improvements not adopted by the people we serve (exercise, nutrition, people we serve (exercise, nutrition, smoking)smoking)

Access to healthcareAccess to healthcare Weight gain from medicationsWeight gain from medications

Sad, irritable or empty moodSad, irritable or empty mood Diurnal variationDiurnal variation Diminished capacity for enjoymentDiminished capacity for enjoyment Diminished interestsDiminished interests Frontal lobe, serotonin, Frontal lobe, serotonin,

norepinephrine, dopamine norepinephrine, dopamine (anhedonia)(anhedonia)

Difficulty concentratingDifficulty concentrating IndecisivenessIndecisiveness Memory problemsMemory problems Depressed content of thoughtDepressed content of thought

WorthlessnessWorthlessness GuiltGuilt HopelessnessHopelessness Death and Suicide Death and Suicide

Frontal lobe, serotonin, norepinephrineFrontal lobe, serotonin, norepinephrine

Sleep disturbancesSleep disturbances Appetite disturbances, weight changesAppetite disturbances, weight changes Fatigue, low energyFatigue, low energy Upset stomach, constipationUpset stomach, constipation Physical painPhysical pain Hypothalamus serotonin, Hypothalamus serotonin,

norepinephrine, histamine (sleep)norepinephrine, histamine (sleep)

Mild to severeMild to severe May include psychosis, poor self care, suicideMay include psychosis, poor self care, suicide

Abraham Lincoln describing his own Abraham Lincoln describing his own depression:depression:

““I am now the most miserable man living. If I am now the most miserable man living. If what I feel were equally distributed to the what I feel were equally distributed to the whole human family, there would not be one whole human family, there would not be one cheerful face on earth. Whether I shall ever cheerful face on earth. Whether I shall ever be better, I cannot tell. I awfully forebode I be better, I cannot tell. I awfully forebode I shall not. To remain as I am is impossible. I shall not. To remain as I am is impossible. I must die or be better, it appears to me.”must die or be better, it appears to me.”

All antidepressants must be taken All antidepressants must be taken for at least 4-6 weeks to have for at least 4-6 weeks to have substantial benefitsubstantial benefit

Studies are showing that if you Studies are showing that if you don’t respond in the first week or don’t respond in the first week or two, you’re probably not going to, two, you’re probably not going to, so augment or change earlier than so augment or change earlier than previously recommended.previously recommended.

Problem in certain brain regions that Problem in certain brain regions that comprise circuitscomprise circuits Frontal lobe- mood, cognition, alertness, Frontal lobe- mood, cognition, alertness,

motivationmotivation Cingulate gyrus-normal expression of Cingulate gyrus-normal expression of

emotionsemotions Caudate-putamen-fine tunes emotions and Caudate-putamen-fine tunes emotions and

movementsmovements Amygdala-anxiety, angerAmygdala-anxiety, anger Hypothalamus-sleeping, eatingHypothalamus-sleeping, eating Hippocampus-memoryHippocampus-memory

Dopamine-reward/reinforcement, anhedoniaDopamine-reward/reinforcement, anhedonia Glutamate-ubiquitous, excitatory, too much Glutamate-ubiquitous, excitatory, too much

kills neurons, stress increases cortisol kills neurons, stress increases cortisol increases glutamate (stress kills nerves), increases glutamate (stress kills nerves), cognition, affects dopamine releasecognition, affects dopamine release

Serotonin- all aspects of depressionSerotonin- all aspects of depression Norepinephrine- all aspects of depressionNorepinephrine- all aspects of depression GABA-ubiquitous, inhibitory, anxiety, cognitionGABA-ubiquitous, inhibitory, anxiety, cognition Acetylcholine-memory, cognition, Acetylcholine-memory, cognition,

Fluoxetine (Prozac)Fluoxetine (Prozac) Sertraline (Zoloft)Sertraline (Zoloft) Paroxetine (Paxil)Paroxetine (Paxil) Citalopram (Celexa)Citalopram (Celexa) Escitalopram (Lexapro)Escitalopram (Lexapro) Fluvoxamine (Luvox)Fluvoxamine (Luvox)

NauseaNausea Dry mouthDry mouth Diarrhea or stomach upsetDiarrhea or stomach upset Lack of appetiteLack of appetite Feeling tired, weak, or dizzyFeeling tired, weak, or dizzy HeadacheHeadache Anxiety or nervousnessAnxiety or nervousness Sexual dysfunctionSexual dysfunction

Bupropion (Wellbutrin, Zyban)Bupropion (Wellbutrin, Zyban) Can cause agitation, anxiety, insomniaCan cause agitation, anxiety, insomnia

Venlafaxine (Effexor, Pristiq)Venlafaxine (Effexor, Pristiq) Hypertension, SSRI-like side effectsHypertension, SSRI-like side effects

Trazodone (Desyrel)Trazodone (Desyrel) Sedation, dizzinessSedation, dizziness

Nefazodone (Serzone)Nefazodone (Serzone) SSRI-like but more sedation, monitor for liver SSRI-like but more sedation, monitor for liver

toxicitytoxicity Mirtazapine (Remeron)Mirtazapine (Remeron)

May cause sedation, weight gainMay cause sedation, weight gain Duloxetine (Cymbalta)Duloxetine (Cymbalta)

May cause nauseaMay cause nausea

Amitriptyline (Elavil)Amitriptyline (Elavil) Clomipramine (Anafranil)Clomipramine (Anafranil) Desipramine (Norpramin)Desipramine (Norpramin) Doxepin (Sinequan)Doxepin (Sinequan) Imipramine (Tofranil)Imipramine (Tofranil) Nortriptyline (Pamelor) Nortriptyline (Pamelor)

Can be fatal in overdoseCan be fatal in overdose Fatigue, sedationFatigue, sedation Light-headedness, dizzinessLight-headedness, dizziness Dry mouthDry mouth ConstipationConstipation Weight gainWeight gain HeadacheHeadache

Isocarboxazid (Marplan)Isocarboxazid (Marplan) Meclobemide (Aurorix)Meclobemide (Aurorix) Phenelzine (Nardil)Phenelzine (Nardil) Tranylcypromine (Parnate)Tranylcypromine (Parnate) Selegiline (Eldepryl)Selegiline (Eldepryl)

Strict dietary restrictionStrict dietary restriction Avoid aged cheeses and meats, soy Avoid aged cheeses and meats, soy

sauce, soy beans, fava beans, wine, sauce, soy beans, fava beans, wine, beer, othersbeer, others

Avoid other anti-depressantsAvoid other anti-depressants Avoid over-the-counter Avoid over-the-counter

medicationsmedications

Hypertensive crisisHypertensive crisis Serotonin syndromeSerotonin syndrome Weight gainWeight gain FatigueFatigue ConstipationConstipation DizzinessDizziness

1% of general population1% of general population Equal in men and womenEqual in men and women Age of onset similar to schizophreniaAge of onset similar to schizophrenia Episodes can come on very fast (1-7 days)Episodes can come on very fast (1-7 days) Later episodes longer, more severe, more Later episodes longer, more severe, more

frequentfrequent Substance abuse commonSubstance abuse common Heredity plays a greater role than in depressionHeredity plays a greater role than in depression Family members also at higher risk for major Family members also at higher risk for major

depressiondepression High suicide riskHigh suicide risk

Persistently elevated, expansive or irritable mood Persistently elevated, expansive or irritable mood for one weekfor one week

Associated symptoms (need 3 or more for diagnosis)Associated symptoms (need 3 or more for diagnosis) Inflated self -esteem or grandiosityInflated self -esteem or grandiosity Decreased need for sleepDecreased need for sleep More talkativeMore talkative Racing thoughts or flight of ideasRacing thoughts or flight of ideas DistractibilityDistractibility Agitation or increase in activitiesAgitation or increase in activities Excessive involvement in pleasurable activities with a high risk for Excessive involvement in pleasurable activities with a high risk for

painful consequencespainful consequences Spending sprees, sexual indiscretions, foolish investmentsSpending sprees, sexual indiscretions, foolish investments

Distinct period of persistently elevated, expansive, or irritable mood, lasting throughout at least 4 days plus three of the following:

inflated self-esteem or grandiosity

decreased need for sleep (e.g., feels rested after only 3 hours of sleep)

more talkative than usual or pressure to keep talking

flight of ideas or subjective experience that thoughts are racing

distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)

increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation

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)

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.

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.

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).

Frontal lobe and amygdala-emotion Frontal lobe and amygdala-emotion regulationregulation

Impulsivity-dopamine Impulsivity-dopamine reward/reinforcementreward/reinforcement

Lack of need for sleep-histamineLack of need for sleep-histamine Increased neuronal firing, glutamateIncreased neuronal firing, glutamate Mood stabilizers may reduce the Mood stabilizers may reduce the

chemicals produced after a nerve fireschemicals produced after a nerve fires

FDA Approved AgentsFDA Approved Agents lithium (Eskalith, Lithobid) (mania, depression)lithium (Eskalith, Lithobid) (mania, depression) valproate (Depakote) (mania)valproate (Depakote) (mania) carbamazepine XR (Tegretol XR) (mania)carbamazepine XR (Tegretol XR) (mania) aripiprazole (Abilify) (mania)aripiprazole (Abilify) (mania) asenapine (Saphris) (mania)asenapine (Saphris) (mania) chlorpromazine (Thorazine) (mania)chlorpromazine (Thorazine) (mania) olanzapine (Zyprexa) (mania)olanzapine (Zyprexa) (mania) olanzapine + fluoxetine (depression)olanzapine + fluoxetine (depression) lamotrigine (Lamictal) (depression prevention)lamotrigine (Lamictal) (depression prevention) risperidone (Risperdal) (mania)risperidone (Risperdal) (mania) quetiapine (Seroquel) (depression, mania)quetiapine (Seroquel) (depression, mania) ziprasidone (Geodon) (mania)ziprasidone (Geodon) (mania)

Toxic in overdoseToxic in overdose Severe tremor, confusion, Severe tremor, confusion,

disorientation, seizure, comadisorientation, seizure, coma Can check blood levelsCan check blood levels TremorTremor Gastrointestinal symptomsGastrointestinal symptoms Increased weightIncreased weight

Monitor blood levelsMonitor blood levels Stomach upsetStomach upset Weight gainWeight gain SedationSedation Liver failureLiver failure

Yellowing of skin or eyes, dark urine, nausea/vomitingYellowing of skin or eyes, dark urine, nausea/vomiting PancreatitisPancreatitis

Abdominal pain, nausea/vomiting, decreased appetiteAbdominal pain, nausea/vomiting, decreased appetite Polycystic Ovary riskPolycystic Ovary risk Hair lossHair loss

Other anticonvulsantsOther anticonvulsants Oxcarbazepine (Trileptal)Oxcarbazepine (Trileptal) Topiramate (Topamax)Topiramate (Topamax) Tiagabine (Gabitril)Tiagabine (Gabitril) Gabapentin (Neurontin)Gabapentin (Neurontin)

Other second generation Other second generation antipsychoticsantipsychotics iloperidone (Fanapt)iloperidone (Fanapt)

Conventional neurolepticsConventional neuroleptics BenzodiazapinesBenzodiazapines

Posttraumatic Stress DisorderPosttraumatic Stress Disorder

Obsessive Compulsive DisorderObsessive Compulsive Disorder

Generalized Anxiety DisorderGeneralized Anxiety Disorder

Panic Disorder with or without Panic Disorder with or without agoraphobiaagoraphobia

SSRIs, SNRIs, TCAs effective in SSRIs, SNRIs, TCAs effective in concert with psychotherapyconcert with psychotherapy

Amygdala mediates fear and Amygdala mediates fear and anxiety, GABA+glutamate balance, anxiety, GABA+glutamate balance, norepinephrine, dopamine, serotoninnorepinephrine, dopamine, serotonin

Frontal lobe mediates increased Frontal lobe mediates increased attention/vigilance, norepinephrineattention/vigilance, norepinephrine

Hypothalamus-blood pressure, Hypothalamus-blood pressure, increased heart rateincreased heart rate

Fluoxetine (Prozac)Fluoxetine (Prozac) Sertraline (Zoloft)Sertraline (Zoloft) Paroxetine (Paxil)Paroxetine (Paxil) Citalopram (Celexa)Citalopram (Celexa) Escitalopram (Lexapro)Escitalopram (Lexapro) Fluvoxamine (Luvox)Fluvoxamine (Luvox)

Bupropion (Wellbutrin, Zyban)Bupropion (Wellbutrin, Zyban) Can cause agitation, anxiety, insomniaCan cause agitation, anxiety, insomnia

Venlafaxine (Effexor, Pristiq)Venlafaxine (Effexor, Pristiq) Hypertension, SSRI-like side effectsHypertension, SSRI-like side effects

Trazodone (Desyrel)Trazodone (Desyrel) Sedation, dizzinessSedation, dizziness

Nefazodone (Serzone)Nefazodone (Serzone) SSRI-like but more sedation, monitor for liver SSRI-like but more sedation, monitor for liver

toxicitytoxicity Mirtazapine (Remeron)Mirtazapine (Remeron)

May cause sedation, weight gainMay cause sedation, weight gain Duloxetine (Cymbalta)Duloxetine (Cymbalta)

May cause nauseaMay cause nausea

Alprazolam (Xanax)Alprazolam (Xanax) Chlordiazepoxide Chlordiazepoxide

(Librium)(Librium) Clonazepam Clonazepam

(Klonopin)(Klonopin) Diazepam (Valium)Diazepam (Valium) Lorazepam (Ativan)Lorazepam (Ativan)

Oxazepam (Serax)Oxazepam (Serax) Temazepam Temazepam

(Restoril)(Restoril) Triazolam Triazolam

(Halcion)(Halcion) Zolpidem Zolpidem

(Ambien)(Ambien) Zaleplon (Sonata)Zaleplon (Sonata)

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Note: all have addiction potential, last four mostly for sleep, GABA in amygdala a major target

SedationSedation Addiction potentialAddiction potential Can be fatal in overdose, especially if Can be fatal in overdose, especially if

combined with alcoholcombined with alcohol Studies show most likely outcome for Studies show most likely outcome for

adding a benzo is to create benzo adding a benzo is to create benzo dependence; either no benefit or dependence; either no benefit or trigger for abusing other substancestrigger for abusing other substances

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Severe craving lengthens tapering off Severe craving lengthens tapering off periodperiod

Taking benzos decreases craving for Taking benzos decreases craving for benzos, alcohol, or other substance of benzos, alcohol, or other substance of abuse, but does not improve illnessabuse, but does not improve illness

Folks with bipolar disorder and depression Folks with bipolar disorder and depression have a very high risk of developing benzo have a very high risk of developing benzo abuse/dependence, with no evidence that abuse/dependence, with no evidence that benzos beneficial for moodbenzos beneficial for mood

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Many states are restricting or Many states are restricting or eliminating benzos from formularyeliminating benzos from formulary

Time-limited, supervised use for Time-limited, supervised use for detox/withdrawal and akasthisia detox/withdrawal and akasthisia now only acceptable use for benzosnow only acceptable use for benzos

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Intending to use the substanceIntending to use the substance Hoping not to get in troubleHoping not to get in trouble Make bad choicesMake bad choices Do get in troubleDo get in trouble Outcome goal- abstinence or non-harmful Outcome goal- abstinence or non-harmful

useuse Dopamine in nucleus accumbens, amygdala Dopamine in nucleus accumbens, amygdala

frontal lobe, temporal lobe (withdrawal frontal lobe, temporal lobe (withdrawal balance of GABA and glutamate)balance of GABA and glutamate)

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Achieve abstinence before Achieve abstinence before treating mood, anxiety or treating mood, anxiety or psychotic disorderpsychotic disorder

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Psychotropic medications Psychotropic medications reduced the likelihood of reduced the likelihood of sobrietysobriety

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No medications available to No medications available to facilitate sobriety (Antabuse-facilitate sobriety (Antabuse-no data on sobriety)no data on sobriety)

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Treat all illnesses Treat all illnesses simultaneously, and combine simultaneously, and combine medications designed to medications designed to enhance sobriety with enhance sobriety with psychosocial interventionspsychosocial interventions

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Harm reduction is a useful Harm reduction is a useful treatment goal as part of the treatment goal as part of the treatment plan. treatment plan.

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Comorbidity is the expectation, not the Comorbidity is the expectation, not the exceptionexception Persons diagnosed with schizophreniaPersons diagnosed with schizophrenia

47% use substances47% use substances 55% of those in psychiatric treatment55% of those in psychiatric treatment

Bipolar disorderBipolar disorder 62% have substance use disorder62% have substance use disorder Bipolar consumers more likely to abuse alcohol and Bipolar consumers more likely to abuse alcohol and

cannabis than MDDcannabis than MDD Major Depressive disorderMajor Depressive disorder

More likely to have alcohol dependence than abuseMore likely to have alcohol dependence than abuse Consumers with mood disorders, in general, are likely to Consumers with mood disorders, in general, are likely to

abuse benzodiazepines.abuse benzodiazepines.

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Provision for basic needsProvision for basic needs Assertive community treatment Assertive community treatment

(ACT)(ACT) Patient and family psychoeducationPatient and family psychoeducation Vocational rehabilitationVocational rehabilitation ClubhousesClubhouses Social skills trainingSocial skills training Support groupsSupport groups

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Motivational enhancement therapyMotivational enhancement therapy Cognitive behavioral (relapse Cognitive behavioral (relapse

prevention)prevention) 12 step programs12 step programs Contingency managementContingency management Family interventionsFamily interventions Self-help manuals/workbooksSelf-help manuals/workbooks Case managementCase management

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There is little evidence that there is There is little evidence that there is a gene that increases likelihood that a gene that increases likelihood that you will have a co-occurring disorderyou will have a co-occurring disorder

There is also little evidence that any There is also little evidence that any one factor “causes” you to develop one factor “causes” you to develop co-occurring disorder (e.g. co-occurring disorder (e.g. personality disorder, “addictive personality disorder, “addictive personality”).personality”).

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There is little agreement whether There is little agreement whether mood disorder symptoms precede or mood disorder symptoms precede or follow substance abusefollow substance abuse

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NO (most of the time)NO (most of the time) Treat both conditions simultaneouslyTreat both conditions simultaneously Yearly schizophrenia relapse rateYearly schizophrenia relapse rate

With medication - 15-20%With medication - 15-20% Without medication - 70%Without medication - 70% Without medication and with precipitant Without medication and with precipitant

such as substance abuse – greater than such as substance abuse – greater than 70%70%

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With deinstitutionalization, more choices including With deinstitutionalization, more choices including self-determinationself-determination

Not just to self-medicate symptomsNot just to self-medicate symptoms Relieves feelings of isolation, loneliness, boredom Relieves feelings of isolation, loneliness, boredom

and despairand despair Facilitates peer interaction and social engagementFacilitates peer interaction and social engagement Promotes a sense of well-being, escape from life Promotes a sense of well-being, escape from life

perceived as bleak or hopeless, mitigates withdrawalperceived as bleak or hopeless, mitigates withdrawal Harder to modify behavior if have cognitive Harder to modify behavior if have cognitive

impairmentsimpairments Increases metabolism, effectively reducing doses of Increases metabolism, effectively reducing doses of

medicationsmedications

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disulfiram (Antabuse)disulfiram (Antabuse)

Works by interfering with alcohol Works by interfering with alcohol metabolism-cousin of formaldehyde metabolism-cousin of formaldehyde accumulates in blood, causing illnessaccumulates in blood, causing illness

Doesn’t affect craving directly, limited Doesn’t affect craving directly, limited data on relapse reductiondata on relapse reduction

More of an aversive treatmentMore of an aversive treatment Avoid alcohol in any form (aftershave, etc)Avoid alcohol in any form (aftershave, etc)

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naltrexone (Revia)naltrexone (Revia)

Works by affecting endogenous opioid Works by affecting endogenous opioid systemsystem

Reduces cravingReduces craving Will induce withdrawal if consumer Will induce withdrawal if consumer

using or abusing opiatesusing or abusing opiates Can’t use opiates for pain managementCan’t use opiates for pain management

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injectible naltrexone (Vivitrol)injectible naltrexone (Vivitrol)

Works by affecting endogenous opioid Works by affecting endogenous opioid systemsystem

Reduces cravingReduces craving Will induce withdrawal if consumer Will induce withdrawal if consumer

using or abusing opiatesusing or abusing opiates Can’t use opiates for pain managementCan’t use opiates for pain management

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acamprosate (Campral)acamprosate (Campral)

Works by affecting glutamate and/or Works by affecting glutamate and/or GABA receptorsGABA receptors

May reduce craving by mitigating early May reduce craving by mitigating early withdrawal, and reduces relapse rateswithdrawal, and reduces relapse rates

Avoid if consumer has kidney problemsAvoid if consumer has kidney problems

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methadone (Dolophine)methadone (Dolophine)

Works by occupying opiate receptors in Works by occupying opiate receptors in same way morphine and its cousins dosame way morphine and its cousins do

Will reduce withdrawal symptoms but Will reduce withdrawal symptoms but some abuse potentialsome abuse potential

Needs to be prescribed in a Needs to be prescribed in a subspecialty clinicsubspecialty clinic

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buprenorphine (Suboxone)buprenorphine (Suboxone)

Works by occupying opiate receptors Works by occupying opiate receptors without fully stimulating themwithout fully stimulating them

Will reduce withdrawal symptoms and Will reduce withdrawal symptoms and may have less abuse potential than may have less abuse potential than methadonemethadone

Prescribers must go through special Prescribers must go through special training in order to prescribetraining in order to prescribe

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imipramine (Tofranil)imipramine (Tofranil)

Used to treat depression in consumer Used to treat depression in consumer with opiate abuse/dependencewith opiate abuse/dependence

Treatment for depression with Treatment for depression with imipramine was associated with imipramine was associated with reduced craving for, and self-reported reduced craving for, and self-reported use of, opiates, cocaine, and cannabisuse of, opiates, cocaine, and cannabis

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Nicotine replacementNicotine replacement

Works same way smoking and Works same way smoking and dipping doesdipping does

May reduce craving by occupying May reduce craving by occupying and stimulating receptorsand stimulating receptors

Available in multiple delivery Available in multiple delivery systemssystems

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buproprion (Zyban, Wellbutrin)buproprion (Zyban, Wellbutrin)

Works through the dopamine and Works through the dopamine and norepinephrine system norepinephrine system (presumably)(presumably)

May reduce craving indirectlyMay reduce craving indirectly Effect independent of Effect independent of

antidepressant effectantidepressant effect75

Varenicline (Chantix)Varenicline (Chantix)

Works by occupying nicotinic receptors, Works by occupying nicotinic receptors, blocking nicotine effectsblocking nicotine effects

May reduce craving by mildly stimulating May reduce craving by mildly stimulating receptorsreceptors

Nicotinic receptors are odd: initially Nicotinic receptors are odd: initially stimulated, then shut downstimulated, then shut down

Insomnia, agitation, psychosis possibleInsomnia, agitation, psychosis possible76

No medication approved for caffeine No medication approved for caffeine use/abuseuse/abuse

Caffeine blocks adenosineCaffeine blocks adenosine Adenosine receptors in brain affect Adenosine receptors in brain affect

wakefulnesswakefulness Adenosine receptors in the heart Adenosine receptors in the heart

regulate rhythmregulate rhythm Adenosine receptors in stomach affect Adenosine receptors in stomach affect

acid secretionacid secretion77

Consumers on clozapine seem to Consumers on clozapine seem to have lower rates of substance have lower rates of substance abuse abuse

Lithium for adolescents seems to Lithium for adolescents seems to reduce alcohol abusereduce alcohol abuse

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Withdrawal from alcohol and Withdrawal from alcohol and benzos can be fatalbenzos can be fatal

Withdrawal from opiates is very Withdrawal from opiates is very uncomfortable, with significant uncomfortable, with significant physical symptoms, but rarely fatalphysical symptoms, but rarely fatal

Withdrawal from cocaine rarely Withdrawal from cocaine rarely requires close supervisionrequires close supervision

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AccessibleAccessible

CapableCapable

ComprehensiveComprehensive

ContinuousContinuous

IntegratedIntegrated

FlexibleFlexible

IndividualizedIndividualized

Willing and Willing and TolerantTolerant

Culturally Culturally competentcompetent

Safe housingSafe housing Meaningful daytime activityMeaningful daytime activity Sober support networkSober support network Positive alliance with at least one Positive alliance with at least one

treatment providertreatment provider Social work interventions reduce stress, Social work interventions reduce stress,

preserving brain function, and leading to preserving brain function, and leading to better outcomesbetter outcomes

Can’t remember

Difficult medication schedule

Fear of medications

Bad side effects

No social support

Don’t have an illness, so don’t need medications

Stigma of taking a psychiatric medication

Don’t like/trust the prescriber

The meds aren’t working

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

Denial-you understand, on some level, your Denial-you understand, on some level, your actions and consequences, but this actions and consequences, but this understanding does not influence behaviorunderstanding does not influence behavior

Anosognosia or lack of insight is the Anosognosia or lack of insight is the physical inability to understand your physical inability to understand your actions while sickactions while sick

Anosognosia is more similar to amnesia Anosognosia is more similar to amnesia than to denialthan to denial

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

Basic tenets of the recovery movement include hope, engagement, supporting self-efficacy, and the dignity of risk

Treatment providers should take a consultative, rather than directive, role in the treatment of psychiatric illnesses; fewer appointments, and more walk-in availability

Note that recovery is not a synonym for symptom remission; consumers can be symptomatic and still participate in society

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

Psychiatric illness associated with increased mortality (life expectancy in your 50s), even when suicide excluded; so…what are we doing?

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!

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)