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: loss of contact with reality
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-IV-TR
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

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

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 a “substantial” portion of total duration of illness
Specify: depressive type or bipolar type

15. Delusional Disorder 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

16. 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

17. 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

18. 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

19. 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

20. Schizophrenia
Epidemiology: ~ 1%. NIMH catchment %, 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

21. Schizophrenia Etiologic Hypotheses:
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)

22. Major Dopamine Pathways
Nigrostriatal pathway1,2
Mesocortical pathway1,2
Controls motor movement
EPS
Associated with cognition and motivation
Mesolimbic pathway1,2
Alogia
Affective flattening
Avolition
Negative symptoms
Associated with memory and emotional behaviors1
Tuberoinfundibular pathway1,2
Controls prolactin secretion
Hyperprolactinemia
Delusions
Hallucinations
Disorganized speech/ thinking
Disorganized or catatonic behavior
Positive symptoms
Four 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.1,2
Positive symptoms include distortions in:2
Thought 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:2
Alogia (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.

23. 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

24. Schizophrenia Substance use: Suicide:
>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

25. Schizophrenia 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 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

26. Schizophrenia CPA 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

27. 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
Less EPS
Aripiprazole: 5HT2a antagonist + partial agonist at D2, 5HT1A

28. 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

29. Atypical Antipsychotics
Risperidone: mg/day start, (2-8mg/d)
Risperidone IM: 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 mg is reached
Quetiapine XR: 300mg day1, 600mg day2, 800mg day3
Aripiprazole: mg/d start, (15-30mg/d)
Ziprasidone: 40mg BID, 60mgBID, 80mg BID, ( mg/d)

30. 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, mg/d possible
Usually 25-50mg IM q 4-6 h prn

31. Clozapine
25 mg qhs and increase nightly in 25 mg increments as tolerated
Target dose: 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

32. Side Effects

33. 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

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

35. 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

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

37. Clozapine Side effects:
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 1st 6 months. Not dose related.
monitor CBC+diff qweekly for 6months, then q2weekly
- myocarditis, cardiomyopathy
-venous thromboembolism, PE, sudden death

38. 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.

39. Extrapyramidal Symptoms (EPS)
Duration of AP tx
EPS
treatment
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

40. Tardive Dyskinesia
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

41. 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.

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

43. 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