Psychosis
Tabitha Rogers MD, MSW, FRCPC
Schizophrenia Program, ROMHC
Assistant Professor, University of Ottawa
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
Differential Diagnosis: Psychosis

Primary Psychotic Disorders
(Schizophrenia, Brief Psychotic Episode, Schizophreniform d/o, Schizoaffective d/o, Delusional Disorder)

Mood Disorders

Substance-related disorders

Mental disorders due to a general medical condition

Dementia

Delirium

Anxiety Disorders- OCD

Personality Disorders, dissociative disorders

Pervasive developmental disorder
(Depression with Psychotic features, Mania)
Case
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).
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.
Case
MSE:
cont’d
“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
Differential Diagnosis: Psychosis

Primary Psychotic Disorders
(Schizophrenia, Brief Psychotic Episode, Schizophreniform d/o, Schizoaffective d/o, Delusional Disorder)

Mood Disorders

Substance-related disorders

Mental disorders due to a general medical condition

Dementia

Delirium

Anxiety Disorders- OCD

Personality Disorders, dissociative disorders

Pervasive developmental disorder
(Depression with Psychotic features, Mania)
Psychotic Disorders
Schizophrenia
Brief Psychotic Episode
Schizophreniform Disorder
Schizoaffective Disorder
Delusional Disorder
Diagnostic Criteria DSM-V
Schizophrenia
 A) 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 of these must be (1), (2), or (3):
 1. Delusions.
 2. Hallucinations.
 3. Disorganized speech (eg, frequent derailment or incoherence)
 4. Grossly disorganized or catatonic behavior.
 5. Negative symptoms (ie, diminished emotional expression or avolition).
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.
Historical Subtypes of Schizophrenia
Catatonic
Disorganized
Paranoid: Characterized by
delusions or auditory hallucinations
Residual
Undifferentiated
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 more of: delusions, hallucinations, disorg speech, or disorg beh
>1day, <1month.
Specify: with/without stressor, or post-partum onset, +/- good prognostic features
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
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.
Risks:
↑age, recent immigration, sensory impairment, brain injury, social isolation.
(NOT fmhx SCZ or mood)
Tx= low dose atypical antipsychotic medication
Back to the case...
The pt is quite agitated, yelling, punching the air.
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

Pharmacologic interventions:
hospital policies
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
Case
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
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
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)
Major Dopamine Pathways
Mesocortical
pathway1,2
• Associated
with cognition
and motivation
Negative symptoms
• Alogia
• Affective flattening
• Avolition
Tuberoinfundibular
pathway1,2
• Controls prolactin secretion
• Hyperprolactinemia
Nigrostriatal
pathway1,2
• Controls motor
movement
• EPS
Mesolimbic
pathway1,2
• Associated
with memory
and emotional
behaviors1
Positive symptoms
• Delusions
• Hallucinations
• Disorganized speech/
thinking
• Disorganized or
catatonic behavior
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.
Schizophrenia
Prognosis:
20-30% live reasonably normal lives
50% moderate to poor prognosis
late and acute onset,
precip stressor, good premorbid funct, mood,
(+)symptoms, supports
Good prognostic factors:
male, early onset,
insidious onset, single, fmhx SCZ, negative
symptoms, no remission, relapses
Poor prognostic factors:
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
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
CPA Guidelines
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
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
Antipsychotics
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
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
Atypical Antipsychotics
 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)
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
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
Side Effects
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
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”
Clozapine
Indications for Clozapine (CPA guidelines)
treatment resistance
 Persistent suicidality
 Persistent violence/aggression
= 2 failed trials of any AP
Clozapine
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
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.
Extrapyramidal Symptoms
(EPS)
Duration of
AP tx
EPS
treatment
Minutes –
hours
Acute Dystonic
Reaction
Benztropine or other
anticholinergic
PO/IM
Torticollis, laryngospasm,
oculogyric crisis
Days
Pseudoparkinsonism
benztropine
Bradykinesia, rigidity, masklike
facies, cogwheel rigidity, perioral
tremor
Days-weeks
Akithisia
Benzodiazepine,
Beta blocker
Long term
Tardive Dyskinesia
Switch to atypical, or
Clozapine.
Often irreversible
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
Case...
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.
Psychosocial Interventions
 Psychoeducation, Medication Adherence
 Vocational interventions
 Skills training
 Family interventions
 Peer support
 Stigma
 CBT
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
Community Resources
 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
Quick Tips for Dealing with
Psychosis in your office
 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