Psychosis
Tabitha Rogers MD, MSW, FRCPC
Schizophrenia Program, ROMHC
University of Ottawa, Department of Psychiatry
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
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
Differential Diagnosis: Psychosis
 Primary Psychotic Disorders
(Schizophrenia, Brief Psychotic Episode, Schizophreniform d/o, Schizoaffective d/o, Delusional Disorder)
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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
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).
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 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
Differential Diagnosis: Psychosis
 Primary Psychotic Disorders
(Schizophrenia, Brief Psychotic Episode, Schizophreniform d/o, Schizoaffective d/o, Delusional Disorder)
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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
Psychotic Disorders
 Schizophrenia
 Brief Psychotic Episode
 Schizophreniform Disorder
Schizoaffective Disorder
 Delusional Disorder
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
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.
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
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
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
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.
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
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
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
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
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
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:
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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
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
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
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
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, Olanzapine, Quetiapine, Ziprasidone
Block D2 receptors + 5HT2a receptors (5HT2a > D2 blockade)
Less EPS
Aripiprazole: 5HT2a antagonist + partial agonist at D2, 5HT1A
Antipsychotics
Choice of antipsychotic:
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Start with an atypical antipsychotic
Previous response
Side effect profile
Medical history
Issues around compliance (consider long acting injection)
Response, treatment resistance
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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.
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)
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)
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Sedation
Postural hypotension
Elevated heart rate
Constipation
Dry mouth
Cognitive dulling
 High Potency (Haloperidol)
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Parkinsonism
Dystonic reactions
Akithesia
Higher TD incidence
 Atypicals
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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 (++ w/ Ziprasidone)
 α1 blockade: dizzy, postural hypotension
 Seizure- reduction of SZ threshold
 Endocrine and sexual side effects: FGA>SGA
quetiapine+clozapine= “prolactin sparing”
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
Clozapine
Indications for Clozapine (CPA guidelines)
treatment resistance = 2 failed trials of any AP
 Persistent suicidality
 Persistent violence/aggression
Clozapine
Mechanism of Action: antagonist at D1-D5, M1, H1,5HT2a, alpha.
Side effects:
common:
sedation, constipation, sialorrhea, dizzy, wt gain, tachycardia,
hypotension
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+diff qweekly for 6months, then
q2weekly for 6 months, then monthly for duration of
treatment.
- 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
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.
Psychosocial Interventions
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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