1Psychosis Tabitha Rogers MD, MSW, FRCPC Schizophrenia Program, ROMHC University of Ottawa, Department of Psychiatry
2Objectives Discuss the differential diagnosis for psychosis Review the primary psychotic disordersReview the treatment guidelines and pertinent clinical information for SchizophreniaProvide an overview of antipsychotic medications
3PsychosisDefinition: from the Greek “psyche” = mind/soul, and –osis = abnormal condition generic psychiatric term for a mental state involving a loss of contact with reality
4Differential Diagnosis: Psychosis Primary Psychotic Disorders(Schizophrenia, Brief Psychotic Episode, Schizophreniform d/o, Schizoaffective d/o, Delusional Disorder)Mood Disorders (Depression with Psychotic features, Mania)Substance-related disordersMental disorders due to a general medical conditionDementiaDeliriumAnxiety Disorders- OCDPersonality Disorders, dissociative disordersPervasive developmental disorder
5CaseID: 19 yr male, recently homeless. Unemployed, limited social supports. RFR: brought to ER by police due to concern over bizarre behaviour (wearing a winter coat during the heat wave, wandering through traffic, talking/yelling to self).
6Case cont’dHistory:Pt is a difficult historian, however you determine that he is from the Toronto area but moved to Ottawa 6 months ago to participate in Parliament as he believes he is the “vice minister”. He reports hearing the voice of God commenting on his actions and commanding him to do things. He believes parliament is infiltrated with demons and he has been appointed to save Canada.He is estranged from his family and has no supports in Ottawa other than staff at the shelter.He was an average student until grade 12 when he became isolative, stopped playing sports, and started smoking marijuana. He did poorly in grade 12 but managed to graduate high school. He enrolled in a local college but did not attend his courses.He has not seen a physician in 4 years, but states he has no medical issues.He has never seen a psychiatrist.He takes no medication.
7Case cont’d MSE: “ASEPTIC” Appearance and Behaviour: Disheveled, malodorous, wearing excessive layers of dirty clothing. Poor eye contact, psychomotor agitation (pacing, talking to self, punching the air)Speech: loud in volume, somewhat monotonousMood: irritableAffect: restricted affect with some labilityPerception: auditory hallucinations – command hallucinations, running commentaryThought process: Moderately to severely disorganized with loosening of associations, neologisms, and tangentialityThought content: bizarre, grandiose, and religious delusionsInsight and Judgment: poorCognition: oriented X3 but attention and concentration poor
8Differential Diagnosis: Psychosis Primary Psychotic Disorders(Schizophrenia, Brief Psychotic Episode, Schizophreniform d/o, Schizoaffective d/o, Delusional Disorder)Mood Disorders (Depression with Psychotic features, Mania)Substance-related disordersMental disorders due to a general medical conditionDementiaDeliriumAnxiety Disorders- OCDPersonality Disorders, dissociative disordersPervasive developmental disorder
10Diagnostic Criteria DSM-V SchizophreniaA) Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated). At least one must be (1), (2), or (3)1. Delusions2. Hallucinations3. Disorganized speech4. Grossly disorganized or catatonic behaviour5. Negative symptoms
11Diagnostic Criteria Schizophrenia: B) social/occupational dysfunction C) 6 months continuous disturbanceD) Not better accounted for by Mood d/o or schizoaffective d/oE) not GMC, substanceF) if PDD, SCZ only if prominent halluc/delus.
12Diagnostic Criteria- Schizophrenia cont’d Specify First episode, currently in acute episode First episode, currently in partial remission First episode, currently in full remission Multiple episodes, currently in acute episode Multiple episodes, currently in partial remission Multiple episodes, currently in full remission Continuous With Catatonic features
13Diagnostic Criteria -Psychotic Disorders cont’d Schizophreniform DisorderCriteria A,D, E of Schizophrenia are met>1month, <6months.Specify if good prognostic features:Rapid onset, confusion at peak, good premorbid function, no affective flatteningBrief Psychotic DisorderOne of: delusions, hallucinations, disorg speech, disorg beh>1day, <1month.Specify: with/without stressor, or post-partum onset, +/- good prognostic features
14Psychotic Disorders- Diagnostic criteria cont’d Schizoaffective DisorderUninterrupted illness where both criteria A for SCZ and mood episode2 weeks delusions/halluc in the absence of mood symptomsMood symptoms present for the “majority” of the total duration of illnessThe disturbance in not due to the effects of a substance or GMC.Specify: depressive type or bipolar type
15Delusional DisorderThe presence of one or more delusions with a duration of 1 month or longerNever met criteria for SCZ. If hallucinations are present they are not prominent and are related to the delusional theme.Other than delusion, function generally unimpaired.If mood symptoms, these have been brief in relation to the delusion.
16Delusional Disorder Types: -persecutory= most common -erotomanic -grandiose-somatic-jealousRisks:↑age, recent immigration, sensory impairment, brain injury, social isolation. (NO fmhx SCZ or mood)Tx= low dose atypical antipsychotic medication
17Back to the case...The pt is quite agitated in ER, yelling, punching the air. In trying to escape from the ER, he has been physically aggressive
18Acute management of agitation Consider Form 1 (request for Psychiatric assessment, 72 hours)Low stimulation environmentRestraints PRN- minimize use, use pharmacologic restraints first, reassess frequently, see hospital policiesPharmacologic interventions:Antipsychotic + BenzodiazepineEx. Haloperidol 5-10mg PO/IM + Lorazepam 1-2mg PO/IM orOlanzapine 10mg IM, 10mg IM in 2 hours if needed max 3 in 24 hours. (do not give IM olanzapine with IM benzo)(note, lower dose in the elderly. Note caution for EPS with haldol)Reassess risk regularly
19CaseThe pt was given Haldol and Lorazepam IM PRN in ER and was more calm. He agreed to take Risperidone 2mg qHS daily, and acute psychotic symptoms improved gradually. Dx- Schizophrenia
21SchizophreniaEpidemiology: ~ 1%. NIMH catchment %, geographical variation (higher in urban, industrialized)Core Symptoms: Positive and negative symptoms, mood symptoms, cognitive symptomsOnset:M:10-25 yrsF: 25-35yrs, bimodal with 2nd peak middle age“late onset”: onset >45yrs- 10% (more women)“very late onset”: onset >60. Rare, more women. Little negative or cognitive symptoms
22Schizophrenia Etiologic Hypotheses: Genetics: MZ 47%, DZ 12%, one parent 12%, both parents 40%Genetic linkage: 22q, 11Etiologic Hypotheses:Dopamine hypothesis5HT (atypical APs are 5HT2A antagonists)NA (low-anhedonia)neurodevel: viral-2nd trimester, nutrition,obstetrical complicationsACh (↓ACh receptors in caudate, hippocampus, PFC)glutamate (NMDA antag→psychosis, agonists can help neg)
23Major Dopamine Pathways Nigrostriatal pathway1,2Mesocortical pathway1,2Controls motor movementEPSAssociated with cognition and motivationMesolimbic pathway1,2AlogiaAffective flatteningAvolitionNegative symptomsAssociated with memory and emotional behaviors1Tuberoinfundibular pathway1,2Controls prolactin secretionHyperprolactinemiaDelusionsHallucinationsDisorganized speech/ thinkingDisorganized or catatonic behaviorPositive symptomsFour well-defined dopamine pathways are illustrated on this slide. The neuroanatomy of these pathways within the CNS may explain both the therapeutic effects and the side effects of antipsychotic agents. The mesolimbic pathway is thought to be involved in behavior related to pleasurable sensations and the powerful euphoria of drugs of abuse, as well as delusions and hallucinations of psychosis. The mesocortical pathway may play a role in mediating the negative and cognitive symptoms of schizophrenia. The nigrostriatal pathway is part of the extrapyramidal nervous system and is believed to control movement. The tuberoinfundibular pathway controls prolactin secretion.1,2Positive symptoms include distortions in:2Thought content (eg, delusions)Perception (eg, hallucinations)Language and thought process (eg, disorganized speech)Self-monitoring of behavior (eg, grossly disorganized or catatonic behavior)Negative symptoms of schizophrenia include:2Alogia (ie, poverty of speech)Affective flattening (ie, reduction in range and intensity of emotional expression)Avolition (ie, diminished goal-directed behavior)1. Kandel ER et al. Principles of Neural Science. 3rd ed. St. Louis, MO: Elsevier; Stahl SM. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 2nd ed. New York, NY: Cambridge University Press; 2000.Kandel ER et al. Principles of Neural Science. 3rd ed. St. Louis, MO: Elsevier; 1991.Stahl SM. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 2nd ed. New York, NY: Cambridge University Press; 2000.
24SchizophreniaPrognosis: 20-30% live reasonably normal lives 50% moderate to poor prognosis Good prognostic factors: late and acute onset, precip stressor, good premorbid funct, mood, (+)symptoms, supports Poor prognostic factors: male, early onset, insidious onset, single, fmhx SCZ, negative symptoms, no remission, relapses
25Schizophrenia Suicide: Substance use: >80% smoke50% lifetime prevalence other substance useSuicide:10-13% complete suicide, 30% attemptrisk suicide: depression, within 6 years of 1st hospitalization, young age, high IQ, high premorbid achievement, awareness of loss of function, command AH, recent dc from hospital, tx nonadherence
26Schizophrenia CPA treatment guidelines Assessment:Acute Phase:- baseline assessment:Positive+Negative symptoms, mood symptoms, SI/HI, disorganization, level of function, substance use screen, CBC, lytes, BUN+CR, LFTs, TSH, lipids, fasting glucose, BMI, endocrine functional inquiry, screen for EPS, cataracts/ocular exam- as clinically indicated: STDs, ECG, genetic testing (22q11 deletion), CT, neuropsych testingStabilization/Stable Phase:BMI: qmonthly for 3 months, then q3monthsEPS: weekly for 2-4 weeks, then q6monthsBP: baseline, at 3 months, then q yearlyBlood sugar: 3 months after starting AP, then q yearlyLipids: baseline, then at 3 months, then at least q 2yearls. (q6months if LDL high)Eye exam: q 2 years up to age 40, then q yearly
27Schizophrenia CPA treatment guidelines PharmacotherapyNo difference between FGAs and SGAs in regard to treatment response for positive symptoms, (except clozapine for treatment-resistant patients)SGAs have a small but significant effect size superiority in the treatment of negative symptoms and cognitive impairmentTx resistance20% multiple episode pts have NO positive symptom response to AP30% respond partiallyTx refractoriness= failed trials of 2 APClozapine is tx of choice
29Antipsychotics Choice of antipsychotic: Start with an atypical antipsychoticPrevious responseSide effect profileMedical historyIssues around compliance (consider long acting injection)Response, treatment resistance
30Atypical Antipsychotics Risperidone: mg/day start, (2-8mg/d)Risperidone IM: mg IM q 2 weeksOlanzapine: 5-10 mg/d start, (10-20 mg/d)Olanzapine IM: 10mg IM can repeat in 2 hours, max 3 doses/24hQuetiapine: 50mg BID with increments of 25-50mg BID each day until mg is reachedQuetiapine XR: 300mg day1, 600mg day2, 800mg day3Aripiprazole: mg/d start, (15-30mg/d)Ziprasidone: 40mg BID, 60mgBID, 80mg BIDLurasidone 40 mg po q hs can increase up to 160 mg po q hs.
31Atypical Antipsycotics Paliperidone: 3 – 9 mg/daySustenna (IM Paliperidone)150 mg IM on first dose, then 100 mg IM 1 week laterThen 75 mg IM q monthly ( mg)Deltoid ( bioavailability)
32Typical Antipsychotics Haloperidol:Range 1-40 mg/d, start low, go slow, watch for EPSEmergency use 10mg IM q 4-6h with ativan and cogentin prnChlorpromazine:Prn use 25-75mg BID-TID, mg/d possibleUsually 25-50mg IM q 4-6 h prn
33Clozapine25 mg qhs and increase nightly in 25 mg increments as toleratedTarget dose: mg/dMonitor HR, BP, Temperature, weekly WBCWeekly WBC x 6 monthsBiweekly WBC x 6 monthsMonthly WBC as tolerated from then on
36Antipsychotics Side effects Wt gain: clozapine+olanzapine significant, risperidone+quetiapine moderateGlucose tolerance, diabetes: all SGAsDyslipidemia: ziprasidone wt and lipid neutralQTc prolongation (++ w/ Ziprasidone)α1 blockade: dizzy, postural hypotensionSeizure- reduction of SZ thresholdEndocrine and sexual side effects: FGA>SGAquetiapine+clozapine= “prolactin sparing”
37Antipsychotics Side effects NMS: Neuroleptic Malignant Syndrome. Rare. fever, autonomic instability, rigidity, granulocytosis, ↓LOC.Mortality 10%Labs: ↑CK, ↑WBC. Can get ↑LFTs, ARF, myoglobinuriaTx: cooling, ICU/supportive, dantrolene, DA agonistsRisks: rapid increase dose, high potency 1st gen, depot, hx NMS or EPS, illness, young male, neuro disability, dehydrationEPS = Extrapyramidal symptomsFGA>SGA
38Clozapine treatment resistance = 2 failed trials of any AP Indications for Clozapine (CPA guidelines)treatment resistance = 2 failed trials of any APPersistent suicidalityPersistent violence/aggression
39Clozapine Side effects: Mechanism of Action: antagonist at D1-D5, M1, H1,5HT2a, alpha.Side effects:common:sedation, constipation, sialorrhea, dizzy, wt gain, tachycardia, hypotension
40ClozapineSevere:SZ: dose>500mg (or if quit smoking—smoking induces CYP1A2)agranulocytosis: 0.5-1%.Risk greatest in 1st 6 months. Not dose related.monitor CBC+diff qweekly for 6months, then q2weekly for 6 months, then monthly for duration of treatment.myocarditis, cardiomyopathyvenous thromboembolism, PE, sudden death
41Back to the case...Within a few days, the patient complains of stiffness which improves with benztropine PRN. After about a week, nursing staff notice that he seems to be restless and pacing. Benztropine has some effect, but he remains subjectively and objectively restless.
42Extrapyramidal Symptoms (EPS) Duration of AP txEPStreatmentMinutes –hoursAcute Dystonic ReactionTorticollis, laryngospasm, oculogyric crisisBenztropine or other anticholinergicPO/IMDaysPseudoparkinsonismBradykinesia, rigidity, masklike facies, cogwheel rigidity, perioral tremorbenztropineDays-weeksAkithisiaBenzodiazepine,Beta blockerLong termTardive DyskinesiaSwitch to atypical, or Clozapine.Often irreversible
43Tardive Dyskinesia5%/year with 1st gen. (25-50% pts tx with 1st gen long term) Due to long-term D2 blockade—receptor sensitivity See when d/c or ↓dose, anticholinergic can exacerbate. Choreoathetoid movements. Orofacial most common, tongue fasiculations early sign. Don’t see in sleep. Stress exacerbates. Monitoring: AIMS (abnormal involuntary movement scale) start, qweekly x one month, then q3months Risk factors: elderly, female, depot, 1st gen, duration use Tx: switch to quetiapine, clozapine, olanzapine. Some evidence for ECT, botox, B6
44Case...Positive symptoms have resolved with Risperidone 2mg qHS You arrange for supportive housing prior to discharge. You refer him to an early pyschosis intervention team where he will have access to SW, OT, Psychiatry. You encourage the pt to find a family physician.
46CBT for Psychosis CPA Schizophrenia Guidelines development of a collaborative understanding of the nature of the illness, which encourages the patient’s active involvement in treatmentidentification of factors exacerbating symptomslearning and strengthening skills for coping with and reducing symptoms and stressreducing physiological arousaldevelopment of problem-solving strategies to reduce relapse