Psychosis

1. Psychosis Tabitha Rogers MD, MSW, FRCPC Schizophrenia Program, ROMHC University of Ottawa, Department of Psychiatry

2. Objectives 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. Psychosis Definition: from the Greek “psyche” = mind/soul, and –osis = abnormal condition generic psychiatric term for a mental state involving a loss of contact with reality

4. Differential 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 disorders • Mental disorders due to a general medical condition • Dementia • Delirium • Anxiety Disorders- OCD • Personality Disorders, dissociative disorders • Pervasive developmental disorder

5. Case ID: 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).

6. Case cont’d 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.

7. Case 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 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

8. Differential 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 disorders • Mental disorders due to a general medical condition • Dementia • Delirium • Anxiety Disorders- OCD • Personality Disorders, dissociative disorders • Pervasive developmental disorder

9. Psychotic Disorders Schizophrenia Brief Psychotic Episode Schizophreniform Disorder Schizoaffective Disorder Delusional Disorder

10. Diagnostic Criteria DSM-V Schizophrenia A) 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. Delusions 2. Hallucinations 3. Disorganized speech 4. Grossly disorganized or catatonic behaviour 5. Negative symptoms

11. Diagnostic Criteria 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.

12. Diagnostic 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

13. Diagnostic Criteria -Psychotic Disorders cont’d 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

14. Psychotic Disorders- Diagnostic criteria cont’d 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 the “majority” of the total duration of illness The disturbance in not due to the effects of a substance or GMC. Specify: depressive type or bipolar type

15. Delusional Disorder • The presence of one or more delusions with a duration of 1 month or longer • Never 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.

16. Delusional Disorder Types: -persecutory= most common -erotomanic -grandiose -somatic -jealous Risks: ↑age, recent immigration, sensory impairment, brain injury, social isolation. (NO fmhx SCZ or mood) Tx= low dose atypical antipsychotic medication

17. Back 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

18. Acute management of agitation 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

19. Case The 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

20. Schizophrenia History: Kraeplin: dementia praecox Bleuler: 4As: loose associations, affective flattening, autism, ambivalence Schneider: 1st rank: audible thoughts, voices discussing, running commentary, somatic passivity, TW, TB, delusional perceptions, volition made impulses/affects 2nd rank: delusions, mood symptoms, perplexity Crow: type I- acute positive symptoms, responds to AP. Type II- chronic, negative symptoms, see atrophy on CT

21. Schizophrenia 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 2nd peak middle age “late onset”: onset >45yrs- 10% (more women) “very late onset”: onset >60. Rare, more women. Little negative or cognitive symptoms

22. Schizophrenia 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-2nd trimester, nutrition,obstetrical complications • ACh (↓ACh receptors in caudate, hippocampus, PFC) • glutamate (NMDA antag→psychosis, agonists can help neg)

23. Nigrostriatalpathway1,2 Mesocorticalpathway1,2 Mesolimbicpathway1,2 Tuberoinfundibularpathway1,2 Positive symptoms • Controls prolactin secretion • Hyperprolactinemia • Delusions • Hallucinations • Disorganized speech/ thinking • Disorganized or catatonic behavior Negative symptoms • Alogia • Affective flattening • Avolition Major Dopamine Pathways • Controls motormovement • EPS • Associated with cognition and motivation • Associated with memory and emotional behaviors1 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.

24. Schizophrenia 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

25. Schizophrenia Substance use: • >80% smoke • 50% lifetime prevalence other substance use Suicide: • 10-13% complete suicide, 30% attempt • risk 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

26. SchizophreniaCPA 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 testing Stabilization/Stable Phase: BMI: qmonthly for 3 months, then q3months EPS: weekly for 2-4 weeks, then q6months BP: baseline, at 3 months, then q yearly Blood sugar: 3 months after starting AP, then q yearly Lipids: 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

27. SchizophreniaCPA treatment guidelines 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

28. Antipsychotics First generation = typical neuroleptics ex. Haloperidol block Dopamine D2 receptors Second generation = atypicals Ex. Clozapine, Risperidone, Olanzapine, Quetiapine, Ziprasidone Block D2 receptors + 5HT2a receptors (5HT2a > D2 blockade) Less EPS Aripiprazole: 5HT2a antagonist + partial agonist at D2, 5HT1A

29. Antipsychotics 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

30. Atypical Antipsychotics Risperidone: 0.5-1 mg/day start, (2-8mg/d) Risperidone IM: 25-75 mg IM q 2 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 Lurasidone 40 mg po q hs can increase up to 160 mg po q hs.

31. Atypical Antipsycotics • Paliperidone: 3 – 9 mg/day • Sustenna (IM Paliperidone) • 150 mg IM on first dose, then 100 mg IM 1 week later • Then 75 mg IM q monthly (75-150 mg) • Deltoid (bioavailability)

32. Typical Antipsychotics • 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

33. Clozapine 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

34. Side Effects

35. General Side-effect Principles • 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

36. Antipsychotics Side effects • Wt gain: clozapine+olanzapine significant, risperidone+quetiapine moderate • Glucose tolerance, diabetes: all SGAs • Dyslipidemia: ziprasidonewt and lipid neutral • QTc prolongation (++ w/ Ziprasidone) • α1 blockade: dizzy, postural hypotension • Seizure- reduction of SZ threshold • Endocrine and sexual side effects: FGA>SGA quetiapine+clozapine= “prolactin sparing”

37. Antipsychotics Side effects NMS: Neuroleptic Malignant Syndrome. Rare. fever, autonomic instability, rigidity, granulocytosis, ↓LOC. Mortality 10% Labs: ↑CK, ↑WBC. Can get ↑LFTs, ARF, myoglobinuria Tx: cooling, ICU/supportive, dantrolene, DA agonists Risks: rapid increase dose, high potency 1st gen, depot, hx NMS or EPS, illness, young male, neuro disability, dehydration EPS = Extrapyramidal symptoms FGA>SGA

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

39. Clozapine Mechanism of Action: antagonist at D1-D5, M1, H1,5HT2a, alpha. Side effects: common: sedation, constipation, sialorrhea, dizzy, wt gain, tachycardia, hypotension

40. Clozapine Severe: • 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+diffqweekly for 6months, then q2weekly for 6 months, then monthly for duration of treatment. • myocarditis, cardiomyopathy • venous thromboembolism, PE, sudden death

41. Back 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.

42. Extrapyramidal Symptoms (EPS)

43. TardiveDyskinesia 5%/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

44. Case... 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.

45. Psychosocial Interventions Psychoeducation, Medication Adherence Vocational interventions Skills training Family interventions Peer support Stigma CBT

46. CBT for Psychosis 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