1. Tabitha Rogers MD, MSW, FRCPC Schizophrenia Program, ROMHC Assistant Professor, University of Ottawa

2.  Discuss the differential diagnosis for psychosis  Review the primary psychotic disorders  Review the treatment guidelines and pertinent clinical information for Schizophrenia  Provide an overview of antipsychotic medications

3.  Primary Psychotic Disorders (Schizophrenia, Brief Psychotic Episode, Schizophreniform d/o, Schizoaffective d/o, Delusional Disorder)  Mood Disorders (Depression with Psychotic features, Mania)  Substance-related disorders  Mental disorders due to a general medical condition  Dementia  Delirium  Anxiety Disorders- OCD  Personality Disorders, dissociative disorders  Pervasive developmental disorder

4. ID: 19 yr male, recently homeless. Unemployed, limited social supports. RFR: brought to your office by a friend. His friend was concerned about bizarre behaviour (wearing a winter coat during the heat wave, wandering through traffic, talking/yelling to self).

5. History: 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.

6. MSE:“ASEPTIC” Appearance and Behaviour: Dishevelled, malodorous, wearing excessive layers of dirty clothing. Poor eye contact, psychomotor agitation (pacing, talking to self, punching the air) Speech: loud in volume, somewhat monotonous Mood: irritable Affect: restricted affect with some lability Perception: auditory hallucinations – command hallucinations, running commentary Thought process: Moderately to severely disorganized with loosening of associations, neologisms, and tangentiality Thought content: bizarre, grandiose, and religious delusions Insight and Judgment: poor Cognition: oriented X3 but attention and concentration poor

7.  Primary Psychotic Disorders (Schizophrenia, Brief Psychotic Episode, Schizophreniform d/o, Schizoaffective d/o, Delusional Disorder)  Mood Disorders (Depression with Psychotic features, Mania)  Substance-related disorders  Mental disorders due to a general medical condition  Dementia  Delirium  Anxiety Disorders- OCD  Personality Disorders, dissociative disorders  Pervasive developmental disorder

8.  Schizophrenia  Brief Psychotic Episode  Schizophreniform Disorder  Schizoaffective Disorder  Delusional Disorder

9. Schizophrenia A) One month with 2 of: (only one if running commentary, bizarre delusions, 2 voices conversing): - delusions -hallucinations - negative symptoms -disorganized speech -disorganized behaviour or catatonic behaviour

10. Schizophrenia: B) social/occupational dysfunction C) 6 months continuous disturbance D) Not better accounted for by Mood d/o or schizoaffective d/o E) not GMC, substance F) if PDD, SCZ only if prominent halluc/delus.

11. Subtypes:  Catatonic: 2 of: -motor immobility (catalepsy or stupor) -excessive purposeless motor - extreme negativism or mutism -peculiar voluntary movement -echolalia or echopraxia  Disorganized: All of: disorganized speech, disorganized behaviour, flat/inappropriate affect  Paranoid: Characterized by delusions or auditory hallucinations  Residual  Undifferentiated

12. Schizophreniform Disorder Criteria A,D, E of Schizophrenia are met >1month, <6months. Specify if good prognostic features: Rapid onset, confusion at peak, good premorbid function, no affective flattening Brief Psychotic Disorder One of: delusions, hallucinations, disorg speech, disorg beh >1day, <1month. Specify: with/without stressor, or post-partum onset, +/- good prognostic features

13. Schizoaffective Disorder  Uninterrupted illness where both criteria A for SCZ and mood episode  2 weeks delusions/halluc in the absence of mood symptoms  Mood symptoms present for a “substantial” portion of total duration of illness Specify: depressive type or bipolar type

14.  Nonbizarre delusions for one month.  Never met criteria for SCZ.  Other than delusion, function generally unimpaired. If mood, duration of mood brief in relation to delusion. Can have tactile or olfactory hallucinations if consistent with delusion. Generally “breeds true”—does NOT progress to SCZ. Types: -persecutory= most common-erotomanic -grandiose-somatic- ex infestation, olfactory -jealous Risks: ↑age, recent immigration, sensory impairment, brain injury, social isolation. (NOT fmhx SCZ or mood) Tx= low dose atypical antipsychotic medication

15. The pt is quite agitated, yelling, punching the air.

16.  Consider Form 1 (request for Psychiatric assessment, 72 hours)  Low stimulation environment  Restraints PRN- minimize use, use pharmacologic restraints first, reassess frequently, see hospital policies  Pharmacologic interventions: Antipsychotic + Benzodiazepine Ex. Haloperidol 5-10mg PO/IM + Lorazepam 1-2mg PO/IM or Olanzapine 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

17. The pt was given Olanzapine 10 mg po and Lorazepam 2 mg po, and was sent to the ER on a Form 1. While in hospital he agreed to take Risperidone 2mg qHS daily, and acute psychotic symptoms improved gradually. Dx- Schizophrenia

18. Epidemiology: ~ 1%. NIMH catchment 0.6-1.9%, geographical variation (higher in urban, industrialized) Core Symptoms: Positive and negative symptoms, mood symptoms, cognitive symptoms Onset: M:10-25 yrs F: 25-35yrs, bimodal with 2 nd peak middle age “late onset”: onset >45yrs- 10% (more women) “very late onset”: onset >60. Rare, more women. L ittle negative or cognitive symptoms

19. Genetics: MZ 47%, DZ 12%, one parent 12%, both parents 40% Genetic linkage: 22q, 11 Etiologic Hypotheses:  Dopamine hypothesis  5HT (atypical APs are 5HT2A antagonists)  NA (low-anhedonia)  neurodevel: viral-2 nd trimester, nutrition,obstetrical complications  ACh (↓ACh receptors in caudate, hippocampus, PFC)  glutamate (NMDA antag→psychosis, agonists can help neg)

20. 1. Kandel ER et al. Principles of Neural Science. 3rd ed. St. Louis, MO: Elsevier; 1991. 2. Stahl SM. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 2nd ed. New York, NY: Cambridge University Press; 2000. Nigrostriatal pathway 1,2 Mesolimbic pathway 1,2 Associated with memory and emotional behaviors 1 Mesocortical pathway 1,2 Associated with cognition and motivation Tuberoinfundibular pathway 1,2 Controls prolactin secretion Hyperprolactinemia Controls motor movement EPS Delusions Hallucinations Disorganized speech/ thinking Disorganized or catatonic behavior Positive symptoms Alogia Affective flattening Avolition Negative symptoms

21. Prognosis: 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

22. Substance use: - >80% smoke - 50% lifetime prevalence other substance use Suicide:  10-13% complete suicide, 30% attempt  risk suicide: depression, within 6 years of 1 st hospitalization, young age, high IQ, high premorbid achievement, awareness of loss of function, command AH, recent dc from hospital, tx nonadherence

23. 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 testing Stabilization/Stable Phase : BMI: qmonthly for 6 months, then q3months EPS: weekly for 2-4 weeks, then q6months Blood sugar: 4 months after starting AP, then q yearly Lipids: at least q 2yearls. (q6months if LDL high) Eye exam: q 2 years up to age 40, then q yearly

24. Pharmacotherapy No 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 impairment Tx resistance 20% multiple episode pts have NO positive symptom response to AP 30% respond partially Tx refractoriness= failed trials of 2 AP Clozapine is tx of choice

25. First generation = typical neuroleptics ex. Haloperidol block Dopamine D2 receptors Second generation = atypicals Ex. Clozapine, Risperidone, Paliperidone, Olanzapine, Quetiapine, Ziprasidone, Asenapine. Block D2 receptors + 5HT2a receptors Less EPS Aripiprazole: 5HT2a antagonist + partial agonist at D2, 5HT1A

26. Choice of antipsychotic:  Start with an atypical antipsychotic  Previous response  Side effect profile  Medical history  Issues around compliance (consider long acting injection)  Response, treatment resistance

27.  Risperidone: 0.5-1 mg/day start, (2-8mg/d)  Risperidone IM: 25-75 mg IM q 2 weeks  Paliperidone 3-12 mg po daily (in the morning)  Sustenna 75-150 mg IM q 4 weeks  Olanzapine: 5-10 mg/d start, (10-20 mg/d)  Olanzapine IM: 10mg IM can repeat in 2 hours, max 3 doses/24h  Quetiapine: 50mg BID with increments of 25-50mg BID each day until 600-800mg is reached  Quetiapine XR: 300mg day1, 600mg day2, 800mg day3  Aripiprazole: 10-15 mg/d start, (15-30mg/d)  Ziprasidone: 40mg BID, 60mgBID, 80mg BID, (40-200 mg/d)

28.  Haloperidol:  Range 1-40 mg/d, start low, go slow, watch for EPS  Emergency use 10mg IM q 4-6h with ativan and cogentin prn  Chlorpromazine:  Prn use 25-75mg BID-TID, 200-800mg/d possible  Usually 25-50mg IM q 4-6 h prn

29.  25 mg qhs and increase nightly in 25 mg increments as tolerated  Target dose: 300-400 mg/d  Monitor HR, BP, Temperature, weekly WBC  Weekly WBC x 6 months  Biweekly WBC x 6 months  Monthly WBC as tolerated from then on

31.  Low potency (chlorpromazine)  Sedation  Postural hypotension  Elevated heart rate  Constipation  Dry mouth  Cognitive dulling  High Potency (Haloperidol)  Parkinsonism  Dystonic reactions  Akithesia  Higher TD incidence  Atypicals  (Olanzapine etc..)  Weight gain  Dyslipidemia  Metabolic syndrome  Type 2 diabetes

32. Side effects  Wt gain: clozapine+olanzapine significant, risperidone+quetiapine moderate  Glucose tolerance, diabetes: all SGAs  Dyslipidemia: ziprasidone wt and lipid neutral  QTc prolongation  α 1 blockade: dizzy, postural hypotension  Seizure- reduction of SZ threshold  Endocrine and sexual side effects: FGA>SGA quetiapine+clozapine= “prolactin sparing”

33. Indications for Clozapine (CPA guidelines)  treatment resistance = 2 failed trials of any AP  Persistent suicidality  Persistent violence/aggression

34. Mechanism of Action: antagonist at D1-D5, M1, H1,5HT2a, alpha. Side effects : common: sedation, sialorrhea, dizzy, wt gain, tachycardia, hypotension Severe: - SZ : dose>500mg (or if quit smoking—smoking induces CYP1A2) - agranulocytosis : 0.5-1%. Risk greatest in 1 st 6 months. Not dose related. monitor CBC+diff qweekly for 6months, then q2weekly - myocarditis, cardiomyopathy -venous thromboembolism, PE, sudden death

35. 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.

36. Duration of AP tx EPStreatment Minutes – hours Acute Dystonic Reaction Torticollis, laryngospasm, oculogyric crisis Benztropine or other anticholinergic PO/IM Days Pseudoparkinsonism Bradykinesia, rigidity, masklike facies, cogwheel rigidity, perioral tremor benztropine Days-weeks Akithisia Benzodiazepine, Beta blocker Long term Tardive Dyskinesia Switch to atypical, or Clozapine. Often irreversible Extrapyramidal Symptoms (EPS)

37. 5%/year with 1 st gen. (25-50% pts tx with 1 st 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, 1 st gen, duration use Tx: switch to quetiapine, clozapine, olanzapine. Some evidence for ECT, botox, B6

38. Positive symptoms have resolved with Risperidone 2mg qHS Supportive housing was arranged prior to discharge. You refer him to an early psychosis intervention team (On Track Phone: 613-737-8069) where he will have access to SW, OT, Psychiatry. You encourage the pt to find a family physician.

39.  Psychoeducation, Medication Adherence  Vocational interventions  Skills training  Family interventions  Peer support  Stigma  CBT

40. CPA Schizophrenia Guidelines  development of a collaborative understanding of the nature of the illness, which encourages the patient’s active involvement in treatment  identification of factors exacerbating symptoms  learning and strengthening skills for coping with and reducing symptoms and stress  reducing physiological arousal  development of problem-solving strategies to reduce relapse

41.  On Track 613-737-8069  Mental Health Crisis Line 613-722-6914  Schizophrenia Society of Ottawa  613-722-6521 ext 7775, 7776  Family information support groups  613-722-6521  NAMI 613-737-7791

42.  Ensure a safe place to interview.  Alert staff  Meds for increased agitation.  Olanzapine 10 mg po with Ativan 2 mg po  Haldol 10 mg po with Ativan 2 mg po  Meds for treatment  Olanzapine 15-20 mg po qhs  Risperidone 2 mg-8 mg po q hs  Paliperidone 6-12 mg po q am  Seroquel XR 600 mg po q 18:00  Asenapine 5 mg po BID  Abilify 15 to 30 mg po daily  Zeldox 80 mg po BID with meals