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1
Schizophrenia:Diagnosis, Treatment
Options and OutcomesElizabeth Montagnese, M.D.
Adult, Child and Adolescent Psychiatrist, Medical Director of Family and Children Services of Central
PennsylvaniaPrivate Practitioner
2
What is schizophrenia?
Theresa- 32 year old woman hospitalized at a State Mental Institution in PANumerous acute hospitalizations in 2 previous years Her psychotic presentation
3
Historical Perspectives
Emil Kraeplin- German psychiatrist in late 1800’sCategorized “dementia praecox” as a disease stateAlso described manic depressionFirst descriptive classification system in psychiatry
4
Emil Kraeplin (contd.)
Viewed mental illness as brain dysfunctionFocused on commonality of symptoms from patient to patientDisturbance of attention, comprehensionHallucinationsDisturbances in flow of thought
5
Eugen Bleuler
Swiss psychiatristElaborated on idea of somatic causeBleuler’s 4A’s: affect, ambivalence, autism, association (loosening of)Proposed specific criteria to diagnosePrimary and secondary symptoms
6
Kurt Schneider
Maximize diagnostic specificityFirst rank symptoms: audible thoughts, voices arguing or commenting, influenced thoughts, delusional perceptionsSecond rank symptoms: perplexity, depression, euphoria, emotional impoverishment
7
Development of DSM
1st DSM- 1952,clinical consensus, universality of diagnostic criteriaDSM II- 1968DSM III- 1972DSM IIIR- 1987, not just clinical consensus but scientific evidenceDSM IV- 1994DSM IVTR- 2000
8
What is psychosis?
What is real vs. fantasyThink of “A Beautiful Mind”
9
Hallucinations
Think of 5 senses: visual, auditory, olfactory, gustatory, tactileUsually frightening, morbid, macabreCan be friendly, company
10
Delusions
A fixed false beliefBizarre-illogicalNonbizarre- can really occur
11
What are the psychotic disorders?
Schizophrenia- 5 typesSchizoaffective DisorderDelusional DisorderBrief Psychotic DisorderShared Psychotic DisorderPsychotic Disorder due to Medical Cond.Substance-induced psychotic disorderPsychotic Disorder NOS (common in kids)
12
DSM Criteria for Schizophrenia
Two or more of following for 1 month: (A Criterion)DelusionsHallucinationsDisorganized speechDisorganized behaviorNegative symptoms: flat affect, avolition, alogiaOnly 1 if delusions bizarre or voice keeping commentary or 2 voices conversing
13
DSM Criteria for Schizophrenia
Social/occupational dysfunctionDisturbance for at least 6 months with at least 1 month with criterion ANot due to substance, medical condition, mood disorder or PDD
14
Schizophrenia Subtypes
CatatonicParanoidDisorganizedUndifferentiatedResidual
15
Positive Symptoms
Symptoms associated withdistorted realityDelusionsHallucinations
Things present in those with schizophrenia as compared to those without.
16
Negative Symptoms
Affective bluntingPoverty of speechThought blockingPoor grooming Lack of motivation-apathyAnhedoniaSocial withdrawal
Things absent from those with schizophrenia as compared to those without.
17
Epidemiology
How common? 1% of world’s populationAcross cultures, racesM:F, 1:1Age of onset is earlier in menM: onset late teens, early 20’sW: onset mid to late 20’sStudies show overdiagnosis in African Americans, not higher incidence
18
Course of Disease
Chronic illnessNo cureVery treatableWithout treatment-downhill course
19
Course of Disease
Impacts morbidity and mortalityCan be “lethal”50% attempt suicide at least 1x10-15% die in 20 yr f/u after diagnosis75% smoke cigarettes30-50% abuse alcohol1/3-2/3 of homeless have schizophrenia
20
Cost of Schizophrenia
1990-accounted for 2.5% of health care expenditures+ nondirect costs($45 billion) 2002- $62.7 billion for direct and nondirect costsUnemployment rate is 70-80%10% of those permanently disabled
21
Treatment prior to antipsychotics
Talk therapyECTInsulin induced seizuresFrontal lobotomiesStraight jacketsWet sheet wraps
22
Treatment
Not just meds but definitely medsPsychosocial and cognitive rehabClubhouse model-deinstitutionalizationSupportive psychotherapyFamily therapy
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Now, let’s get to the meds
Antipsychotics revolutionized treatmentChlorpromazine (Thorazine) – 19521st of the “Typical” antipsychoticsFirst used as an anesthestic
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Conventional Antipsychotics
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Generic Name
Brand Name Dose Equiv.(mg)
Common Dose Range
Relative Potency
EPS
Chlorproma-zine
Thorazine 100 200-900 Low Low
Mesorida-zine
Serentil 50 100-400 Low Low
Thiorida-zine
Mellaril 100 200-800 Low Low
Perphena-zine
Trilafon 8 16-64 Intermediate Intermediate
Trifluopera-zine
Stelazine 5 5-40 High High
Fluphena-zine
Prolixin 2 5-20 High High
Haloperidol Haldol 2 5-20 High HighChlorprothi-
xeneTaractan 75 100-600 Low Low
Thiothixene Navane 5 5-60 High LowLoxapine Loxitane 15 25-250 Intermediate Intermediate
Molindone Moban 10 50-225 Intermediate Intermediate
26
Neuroanatomy 101
Neuron- brain cells, 100 trillion cellsWe lose them as we ageCommunicate with each other via chemical called neurotransmittersPsychotropic medications affect these neurotransmitters
27
How do these meds work?
Target dopamanergic neuronsIncrease dopamine=psychosisDopamine blockersTypical agents affect nigrostriatal tract andmesolimbic tractNigrostriatal area also affects involuntary movementsReason for EPS
28
Extra Pyramidal Symptoms
Akathesia-uncontrolled restlessnessDystonic reactions- muscle spasms, usually eyes, neck, back and tongueParkinsonism- shuffling gait, stiffness, tremor, masked facesCan be intolerable, very frighteningCommon reason for medication noncompliance
29
Acetylcholine-Dopamine Balance
DA
ACHDA
ACH
Excess ACH- high EPS, decreased psychosis
Excess DA-psychosis
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EPS (Contd.)
Higher incidence with higher potencyHigher incidence at start of txRisk factors for EPS: young age, male, IM administrationTreat with anticholinergic or antihistaminergicPrevent with anticholinergic or antiparkinsoniandrugs
31
Treating EPS
Generic Name Trade Name Dose (mg/day) Duration of Action (hrs)
Benztropine mesylate
Cogentin 0.5-6mg 24
Trihexyphenidyl hydrochloride
Artane 1-15 6-12
Amantadine Symmetrel 100-300 12
Diphenhydramine Benadryl 25-150 8
Propranolol Inderal 20-120 8
32
Tardive Dyskinesia
Tardive dyskinesiaAbnormal involuntary movementsDyskineticChoreoathetoidUsually face, tongue, mouthCan involve trunk, armsCan occur after brief exposureStop meds, lower doseCan be permanentMust get informed consent
Risk increases with longer use (4%/yr tx)Risk increases with age, female gender, affective disorder, GMC, high dosesCan be disfiguringClozapine may helpVit E, lithium, amantadine
33
Atypical Agents
NewerAffect D2 and 5HT(2A) receptorsReason for increased efficacyAffects positive (D2) and negative (5HT) symptomsDon’t effect nigrostriatal tract as much-less EPSAffect mesolimbic and mesocortical tracts
34
Atypical Agents
Generic Name Trade Name Daily Dosage(mg)
Forms available
Aripiprazole Abilify 10-30 INJ, soln, tabs-D
Clozapine Clozaril 25-900 tabs-D
Olanzapine Zyprexa 5-20 INJ, tabs-D
Palipaeridone Invega 6-12 tabs
Quetiapine Seroquel 300-800 tabs
Risperidone Risperdal 1-12 tabs-D, soln, INJ
Ziprasidone Geodon 40-160 tabs
35
How do we choose an atypical?
Side effect profile- make them work for patientAny absolute contraindications or medical risksOther meds: drug-drug interactionsCost!!!!InsurancePatient/family perceptionsDoctor’s own perceptions about meds
36
General Side Effects of Atypicals
Less likely to cause EPS or TDProlactin elevation-galactorhea, gynecomastiaSedationAnticholinergicWeight gainAlso seen with typicals
37
Risperidone (Risperdal)
1993Only depot form of atypicalDepot form q 2 weeksWeight gain, sedation and high prolactin most commonAbove 6 mg daily- EPS
38
Olanzipine (Zyprexa)
Very sedatingExcessive weight gainMetabolic syndrome
39
Quetiapine (Seroquel)
Moderate for weight gainSlit lamp eye exam recommended-cataracts, not often doneVery sedatingUsed in low doses for sleep-off label
40
Ziprasidone (Geodon)
2001Short acting injectable availableCan be used for acute agitationMore weight neutral than other atypicalsLower incidence of metabolic syndrome
41
Aripiprazole (Abilify)
Not a full DA agonist“Dopamine stabilizer”Agonist in areas of low activityMore weight neutralLow incidence of metabolic syndrome
42
Clozapine (Clozaril)
1989Weight gainAgranulocytosis- serious, fatal Weekly WBC countSpecific protocol-complex to manageUsed in refractory casesSeizuresExcessive salivation
43
Palipaeridone (Invega)
2007Active metabolite of risperidoneSlow release over 24 hours
Comparison of Atypicals
Typicals Cloz Arip Olanz Risp Que Zip
Prolactin Elev
+ to ++ 0 0 to + + ++ + +
Weight Gain
++ +++ 0 to+ +++ ++ to +++
++ 0 to +
Anticholinergic
+ to +++
+++ +/- +/- + +/- +/-
Sedation + to ++ +++ 0 to +/- +++ ++ +++ 0 to +/-
Cloz=clozapine, Arip=aripiprazole, Olanz=olanzapine, Risp=risperidone, Que=quetiapine, Zip=ziprasidone
45
Are Atypicals Worth It?
CATIE-Sept 2005NIMH study in NEJMGround breakingOutcome stated typicals=atypicals in efficacyCost of atypicals may not always be justifiedPatients stopped both meds at a high rate
46
Cost of Meds
Medication Typical monthly cost
Aripiprazole(Abilify) $500
Paliperidone(Invega) $400
Ziprasidone(Geodon) $400
Risperidone(Risperdal) $200
Clozapine(Clozaril) $300
Quetiapine(Seroquel) $400
Olanzapine(Zyprexa) $350
Haloperidol(Haldol) $45
Perphenazine(Trilafon) $25
47
Use of Atypicals in Children
ControversialMostly off label useAutism spectrum disordersSevere behavioral problemsHugh increase in RXs written for kids in last 5 years.
48
Atypicals-other uses
Bipolar disorder- FDA approvalOCD-severe, refractoryDementia- in past, black box warning
49
Treatment- 3 phases
Phase I- acute phasePrevent harmControl disturbed behaviorReduce psychosisReturn to best level of functioningPatient/family allianceFormulate short and long term treatment palnsConnect with community aftercare
50
Phase II- Stabilization
Minimize risk of relapseMaximize adaptation to return to communityContinue symptom reductionConsolidate recoveryPromote recovery
51
Phase III- Stable Phase
Sustain remissionMaintain or improve functioning and quality of lifePromptly treat symptom exacerbation/relapseMonitor for side effects
Case Study
References
Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Text Revision, American Psychiatric Association, 2000Physicians Desk Reference, 2008Schizophrenia, A Clinician’s Guide, 1995, American Psychiatric PressLieberman JA, Stroup TS, McEvoy JP, et al, “Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia”, N Engl J Med, 2005;353: 1209-1223NIMH, Questions and Answers about the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness Study (CATIE), http://www.nimh.gov/healthinformation.catieqa.cfmWu EQ, Birnbaum HG, et al,“The Economic Burden of Schizophrenia in the United States in 2002”, JClinPsych, 2005 Sept;66(9):1122-1129 Practice Guidelines for the Treatment of Patients with Schizophrenia, Second Edition, 2002, American Psychiatric Association