Psychosis

Tabitha Rogers MD, MSW, FRCPCSchizophrenia Program, ROMHC

University of Ottawa, Department of Psychiatry

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

Objectives

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

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

Differential Diagnosis: Psychosis

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

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 monotonousMood: irritableAffect: restricted affect with some labilityPerception: auditory hallucinations – command hallucinations, running

commentaryThought process: Moderately to severely disorganized with loosening

of associations, neologisms, and tangentialityThought content: bizarre, grandiose, and religious delusionsInsight and Judgment: poorCognition: oriented X3 but attention and concentration poor

Case cont’d

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

Differential Diagnosis: Psychosis

Schizophrenia Brief Psychotic Episode Schizophreniform Disorder Schizoaffective Disorder Delusional Disorder

Psychotic Disorders

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. Delusions2. Hallucinations3. Disorganized speech4. Grossly disorganized or catatonic behaviour5. Negative symptoms

Diagnostic Criteria DSM-V

Schizophrenia:B) social/occupational dysfunctionC) 6 months continuous disturbanceD) Not better accounted for by Mood d/o or

schizoaffective d/oE) not GMC, substanceF) if PDD, SCZ only if prominent halluc/delus.

Diagnostic Criteria

Specify

First episode, currently in acute episodeFirst episode, currently in partial remissionFirst episode, currently in full remission

Multiple episodes, currently in acute episodeMultiple episodes, currently in partial remissionMultiple episodes, currently in full remission

Continuous

With Catatonic features

Diagnostic Criteria- Schizophrenia cont’d

Schizophreniform DisorderCriteria 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 DisorderOne of: delusions, hallucinations, disorg speech, disorg beh>1day, <1month. Specify: with/without stressor, or post-partum onset, +/-

good prognostic features

Diagnostic Criteria -Psychotic Disorders 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 

Psychotic Disorders- Diagnostic criteria cont’d

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

Delusional Disorder

The pt is quite agitated in ER, yelling, punching the air.

In trying to escape from the ER, he has been physically aggressive

Back to the case...

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 + BenzodiazepineEx. 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

Acute management of agitation

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

Case

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/affects2nd 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 yrsF: 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)

Schizophrenia

Major Dopamine Pathways

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.

Nigrostriatalpathway1,2

Mesolimbicpathway1,2

• Associated with memory and emotional behaviors1

Mesocorticalpathway1,2

• Associated with cognition and motivation

Tuberoinfundibularpathway1,2

• Controls prolactin secretion• Hyperprolactinemia

• Controls motormovement

• EPS

• Delusions• Hallucinations • Disorganized speech/

thinking• Disorganized or

catatonic behavior

Positive symptoms

• Alogia• Affective flattening• Avolition

Negative symptoms

Prognosis: 20-30% live reasonably normal lives50% moderate to poor prognosis

Good prognostic factors: late and acute onset, precip stressor, good premorbid funct, mood, (+)symptoms, supportsPoor 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

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 q3monthsEPS: weekly for 2-4 weeks, then q6monthsBP: baseline, at 3 months, then q yearlyBlood 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

SchizophreniaCPA treatment guidelines

PharmacotherapyNo 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 resistance20% multiple episode pts have NO positive

symptom response to AP30% respond partiallyTx refractoriness= failed trials of 2 APClozapine is tx of choice

SchizophreniaCPA treatment guidelines

First generation = typical neurolepticsex. Haloperidolblock Dopamine D2 receptors

Second generation = atypicalsEx. 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:

Start with an atypical antipsychotic Previous response Side effect profile Medical history Issues around compliance (consider long acting

injection) Response, treatment resistance

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 Antipsychotics

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)

Atypical Antipsycotics

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

Typical Antipsychotics

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

Clozapine

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

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, myoglobinuriaTx: cooling, ICU/supportive, dantrolene, DA agonistsRisks: rapid increase dose, high potency 1st gen, depot, hx NMS

or EPS, illness, young male, neuro disability, dehydration

EPS = Extrapyramidal symptomsFGA>SGA

Antipsychotics

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

Clozapine

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.

Back to the case...

Duration of AP tx

EPS treatment

Minutes –hours

Acute Dystonic ReactionTorticollis, laryngospasm, oculogyric crisis

Benztropine or other anticholinergicPO/IM

Days PseudoparkinsonismBradykinesia, 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)

5%/year with 1st gen. (25-50% pts tx with 1st gen long term)

Due to long-term D2 blockade—receptor sensitivitySee 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

Tardive Dyskinesia

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.

Case...

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

Psychosocial Interventions

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

CBT for Psychosis