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Schizophrenia Flashcards

1
Q

psychosis/psychotic episode

A
  • acute and severe ep of mental condition
  • out of touch with reality (disordered thought process, beliefs, perceptions)
  • lack of insight
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2
Q

Definition of Schizophrenia

A
  • common form of protracted psychosis for > 6 months
  • heterogenous syndrome of disorganised and bizarre thoughts, delusions, hallucinations, impaired psychosocial functioning
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3
Q

primary pathophysiology of Schizophrenia

A
  • abnormality in neurotransmitters (dopaminergic (DA), serotonergic (5-HT)
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4
Q

predisposing factors for Schizophrenia

A

1) genetics

  • chromosomes 6, 8, 13, 15, 22

2) environmental in utero
3) neurodevelopmental effect
4) personality
5) physical, psychological and social factors in infancy and early childhood

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5
Q

precipitating factors for Schizophrenia

A

1) Cerebral tumour/injury
2) drug/substance induced psychosis

  • need to rule out immediately
  • alcohol, benzodiazepine, barbiturate, antidepressant, corticosteroids, CNS stimulants (amphetamine), hallucinogens, beta blockers, dopamine agonist (levodopa)

3) personal misfortune
4) environment of high expressed emotion

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6
Q

perpetuating factors for Schizophrenia

A

1) Secondary demoralisation
2) social withdrawal
3) lack of support/poor socioeconomic status/environment
4) poor adherence to meds

  • more relapse = more resistant development = harder to treat
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7
Q

DSM-5 criteria for Schizophrenia

A

1) 2 or more of following for at least 1 month period

  • delusion
  • hallucination
  • disorganised speech
  • grossly disorganised or catatonic behaviour (not aware of surrounding)
  • negative symptoms
    ** affective flattening: feel emotions but don’t show
    ** avolition: total lack of motivation

2) social or occupational dysfunction

  • significant portinon of time since onset of disorder
  • ≥ 1 major area of functioning: work, interpersonal relations, self-care below level prior to onset

3) duration

  • continuous signs of disorder for at least 6 months
  • include at least 1 month of symptoms in first criteria
  • prodromal or residual symptoms

4) excluded Schizoaffective or mood disorder
5) disorder not due to mental disorder or substance abuse
6) if history of pervasive developmental disorder present then at least 1 month of hallucination/delusions

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8
Q

components for Schizophrenia diagnosis

A

1) history of presenting illness
2) psychiatric history: neurosis, psychosis
3) substance use history
4) complete medical history and medication history
5) family, social, forensic, developmental, occupational history
6) physical and neurologic exam
7) mental state exam (MSE)

  • suicidal homicidal ideation and risk
  • reassess MSE on every interview

8) lab and other investigations

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9
Q

lab and other investigations for Schizophrenia diagnosis

A

1) vital signs
2) weight and BMI
3) FBC, SCr, LFT, TFT, ECG, lipid panel (antipsychotics increase BG and TG), urine toxicology
4) PGx for CYP2D6 and CYP2C19 for dose titration

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10
Q

non-pharmacological for Schizophrenia

A

1) individual cognitive behaviour therapy (CBT)

  • conjunction w medication and family intervention
  • process thoughts and understand why patients feels a certain way

2) neurostimulation

  • electroconvulsive therapy (ECT)
    ** for treatment-resistant Schizophrenia
  • Repetitive transcranial magnetic stimulation
    ** reduce auditory hallucination

3) psychosocial rehabilitation programmes

  • help improve adaptive functioning
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11
Q

tldr phases of Schizophrenia treatment

A

1) acute stabilistation
2) stabilisation
3) stable/maintenance phase

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12
Q

acute stabilisation phase for Schizophrenia

A
  • reduce acute symptoms (reduce agitation/aggression/hostility, improve sleep)
  • remove threat to self and others
  • if acutely agitated/aggressive

** de-escalate
** consider oral antipsychotics +/- benzodiazepine
** if refuse/not possible to administer antipsychotic then fast acting IM alternative w monitoring

  • monitor for treatment-emergent AE
    ** dystonia, pseudo-parkinsonism SE, vitals
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13
Q

stabilisation phase for Schizophrenia

A
  • minimise/prevent relapse
  • promote medication adherence
  • optimise dose and manage AE
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14
Q

stable/maintenance phase for Schizophrenia

A
  • improve functioning and QoL
  • maintain baseline functioning
  • optimise dose vs AE
  • monitor for prodromal symptoms of relapse
  • monitor and manage SE
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15
Q

types of typical antipsychotics (FGA)

A
  • chlorpromazine (CPZ)
  • haloperidol (Halo)
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16
Q

MOA of FGA

A
  • block mesolimbic tract
    ** block D2 receptor -> block dopamine mesolimbic (ML) tract -> block overactivity in region causing positive symptoms
    ** tranquilise patient wo impairing consciousness + wo causing paradoxical excitement
  • block 3 other dopamine pathways that result in AE

1) mesocortical (MC) tract
** responsible for higher-order thinking and executive functions
** dopamine blockade = negative symptoms

2) nigrostriatal (NS) tract
** responsible for body movement
** dopamine blockade = EPSE

3) tuberoinfundibular (TI) Tract
** responsible for prolactin secretion
** dopamine blockade = hyperprolactinemia

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17
Q

types of atypical antipsychotics (SGA)

A
  • aripriprazole (Ari)
  • clozapine (cloz)
  • olanzapine (Olan)
  • quetiapine (Quet)
  • risperidone (Risp)
  • amisulpride
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18
Q

MOA of SGA

A
  • mesolimbic tract (same as FGA)
  • greater affinity at 5-HT2A -> block the other 3 tracts to lesser extent -> lesser EPSE
  • more metabolic SE so need monitor
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19
Q

receptor affected vs effects

A

1) D2 antagonism

  • improve positive symptoms
  • SE: EPSE, hyperprolactinemia

2) 5-HT1A agonism

  • anxiolytic

3) 5-HT2A antagonism

  • antidepressant, improve negative symptoms, antipsychotic effects

4) 5-HT2C antagonism

  • SE: weight gain

5) H1 antagonism

  • SE: sedation, weight gain

6) alpha 1 antagonism

  • SE: orthostasis, sedation

7) M1 antagonism

  • SE: memory dysfunction, peripheral anticholinergic effect

8) IKr antagonism

  • SE: QTc prolongation (pro-arrhythmic)
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20
Q

treatment algorithm for Schizophrenia

A

1) diagnosis
2) use single FGA/SGA (except clozapine)

  • if adequate response, no intolerable SE, compliant then continue treatment

3) if CMI then switch to another FGA/SGA except clozapine

  • if adequate response, no intolerable SE, compliant then continue treatment

4) if CMI then consider

  • clozapine monotherapy
    ** when to start?
    a) treatment resistant schizophrenia: failed ≥ 2 adequate trials of different antipsychotics
    b) completed mandatory haematological monitoring every wk for 18 wks
    c) treatment refractory evluation
    ** if adequate response, no intolerable SE, compliant then continue treatment
  • clozapine + augmenting agent (FGA/SGA/ECT)
  • combination therapy
    ** if refusal/intolerable SE to clozapine
    ** possible combinations
    a) 2 antipsychotics
    b) antipsychotics + ECT/ other agents (mood stabilisers)
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21
Q

dosing and efficacy of antipsychotics

A

1) haloperidol

  • very potent so low dose to exert effect

2) quetiapine

  • less potent than haloperidol so higher dose to exert effect

3) olanzapine

  • as potent as haloperidol but weaker D2 antagonism to mid potency D2 antagonist

4) clozapine

  • split dose to BD to prevent seizure/severe hypotension

5) risperidone

  • most commonly used, potent SGA so serotonergic modulation as well
22
Q

precautions for Schizophrenia therapy

A

1) CVD

  • QTc prolongation
  • ECG required esp if CVS risk factors/personal history

2) PD

  • EPSE worsened by antipsychotics

3) epilepsy and conditions predisposing to seizure
4) depression
5) myasthenia gravis, prostatic hypertrophy, angle-closure glaucoma
6) severe respiratory disease
7) history of jaundice
8) blood dyscrasia (Esp clozapine)
9) elderly w dementia

23
Q

antipsychotics PK

A

1) mostly rapidly absorbed and fast onset

  • except brexiprazole, olanzapine, aripiprazole

2) mostly have long t1/2 so can OD dosing

  • except amisulpride, clozapine, quetiapine, ziprasidone
  • need to inquire risk of hypotension and seizure
  • OD dosing at night cuz sedative effect

3) lurasidone/ziprasidone w/after food increase F

24
Q

TLDR antipsychotic SE

A

1) EPSE
2) hyperprolactinemia
3) metabolic
4) CVS
5) CNS
6) hepatic
7) ophthalmologic
8) dermatological
9) haematological

25
Q

antipsychotic SE - EPSE - types

A

1) dystonia
2) pseudo-parkinsonism
3) akathisia
4) tardive dyskinesia

26
Q

antipsychotic SE - EPSE - dystonia

A
  • muscle spasm, occur within mins (IM/IV) or hrs (PO)
  • risks
    ** high potency antipsychotics
  • management
    ** IM anticholinergics
    ** switch to lower potency antipsychotics
27
Q

antipsychotic SE - EPSE - pseudo-parkinsonism

A
  • tremor, rigidity, bradykinesia, bradyphrenia, salivation
  • risk
    ** elderly female, previous neurological damage
  • management
    ** Reduce antipsychotic dose or switch to SGA
    ** anticholinergic PRN
28
Q

antipsychotic SE - EPSE - akathisia

A
  • restlessness, onset hours to weeks
  • management
    ** reduce antipsychotic dose or switch to SGA
    ** low dose clonazepam PRN
    ** propranolol TDS
29
Q

antipsychotic SE - EPSE - tardive dyskinesia

A
  • orofacial movements: lip chewing, tongue protrusion
  • choreiform hand movements, hip thrusting
  • risks
    ** FGA > SGA
    ** worsen with anticholinergic drugs
  • management
    ** discontinue any anticholinergic drugs
    ** decrease antipsychotic dose or switch to SGA
    ** valbenazine
    ** clonazepam PRN
30
Q

antipsychotic SE - hyperprolactinemia

A
  • galactorrhea, amenorrhea, decreased libido, gynecomastia
  • management: switch to aripiprazole
31
Q

antipsychotic SE - metabolic

A
  • weight gain (>7% from baseline), DM, increased lipids
  • risk
    ** high: olan, cloz
    ** low: ari, halo
  • management
    ** lifestyle mod
    ** treat DM (metformin) and hyperlipidemia
    ** switch to lower risk agents
32
Q

antipsychotic SE - CVS - types of SE

A

1) orthostatic hypotension
2) QTc prolongation
3) VTE/PE

33
Q

antipsychotic SE - CVS - orthostatic hypotension

A
  • risks
    ** CPZ & cloz > risp & quet > olan, ari, sulpride
  • management
    ** switch to lower risk agents
    ** get up slowly from sitting/lying position
34
Q

antipsychotic SE - CVS - QTc prolongation

A
  • risks
    ** high doses, IV haloperidol, low K, ischaemic heart disease, female
    ** CPZ > halo > quet > risp > olan
  • management
    ** males > 440ms or females > 470ms then switch to lower risk agents
    ** if > 500ms then refer to cardio
35
Q

antipsychotic SE - CVS - VTE/PE

A
  • risks
    ** low potency FGA
  • management
    ** prevent, monitor, treat emergency DVT
36
Q

antipsychotic SE - CNS - types

A

1) sedation
2) seizure
3) neuroleptic malignant syndrome (NMS)
4) psychogenic polydipsia
5) temperature dysregulation

37
Q

antipsychotic SE - CNS - sedation

A
  • risk
    ** CPZ & cloz > quet > olan > risp, ari
  • management
    ** switch to lower risk agent
    ** early evening administration or OD if possible
38
Q

antipsychotic SE - CNS - seizure

A
  • risk
    ** cloz, CPS higher risk than others
  • management
    ** switch to high potency agents (Halo)
39
Q

antipsychotic SE - CNS - neuroleptic malignant syndrome (NMS)

A
  • symptoms
    ** muscle rigidity, fever, autonomic dysfunction (increase PR, labile BP, diaphoresis), altered consciousness, increased CK
  • risks
    ** higher potency antipsychotics, onset hours to 3 days (Within 30 days)
  • management
    ** IV dantrolene, oral dopamine agonist, supportive measures
    ** switch to SGA
40
Q

antipsychotic SE - CNS - psychogenic polydipsia

A
  • risk
    ** anticholinergics
  • management
    ** fluid restrictions, stop anticholinergics
41
Q

antipsychotic SE - CNS - temperature dysregulation

A
  • risk
    ** anticholinergics
  • management
    ** hydration, appropriate clothing/shade
42
Q

antipsychotic SE - hepatic

A
  • increase LFT (benign), cholestatic jaundice
  • risk
    ** CPZ, olan, quet higher risk than other SGA
  • management
    ** if jaundice occur then discontinue and switch to safer options
43
Q

antipsychotic SE - ophthalmologic

A
  • cornea/lens change, pigmentary retinopathy
  • risk
    ** CPZ, quet
  • management
    ** if patient on quet then eye exam every q6 month
44
Q

antipsychotic SE - dermatological

A
  • maculopapular rash, photosensitivity, pigmentation
  • risk
    ** CPZ
  • management
    ** protective clothing, sunscreen
    ** consider switch to others
45
Q

antipsychotic SE - haematological

A
  • decreased WBC, agranulocytosis
  • risk: clozapine
  • management: discontinue if severe (WBC < 3x10^9/L or SNC < 1.5x10^9/l)
46
Q

monitoring for antipsychotic SE

A

1) BMI

  • weekly for 1st 6 wk then every visit for 6 months (at least monthly for 3 months if SGA)
  • q3 month when dose stabilise

2) waist circumference

  • every visit for 6 months then annually

3) FBG

  • low risk: annually
  • high risk: 4 months after initiating FGA, 3 months for SGA then annually

4) lipid panel

  • low risk: q2-5 yrs
  • high risk: 3 month after initiating SGA, if not q6 month

5) plasma prolactin

  • at baseline

6) blood pressure

  • 3 month after initiating SGA then annually

7) EPSE exam (rigidity, tremor, akathisia, tardive dyskinesia)

  • weekly for 1st 2 wks after initiating new antipsychotic or until dose stabilise
  • low risk: FGA q6 month, SGA q12 month
  • high risk: FGA q3 month, SGA q12 month

8) clozapine specific

  • WBC and ANC weekly for first 18 wks then annually
47
Q

special populations for antipsychotics

A

1) pregnancy

  • olanzapine, clozapine
  • watch for gestational DM

2) breastfeeding

  • olanzapine, quet
  • X clozapine

3) renal impairment

  • oral aripiprazole
  • X sulprides

4) hepatic impairment

  • prefer sulprides

5) elderly

  • avoid drugs w high propensity for alpha-1 adrenergic blockade or anticholinergic SE
  • start low, go slow, simplify routine
48
Q

drug interactions for antipsychotics

A

1) additive CNS depressant effect
2) antimuscarinic, antihistaminic, alpha-1 adrenergic blockade or dopamine blockade
3) dopamine augmenting agents

  • mutual antagonism w antipsychotics

4) anti-HTN

  • increase hypotensive effect

5) CYP inducers and inhibitors

  • CYP1A2 inducers
    ** rifampicin, phenobarbitone, phenytoin, smoking
    ** decrease antipsychotic serum concentration
  • CYP1A2 inhibitors
    ** fluvoxamine, quinolones, macrolides
    ** increase antipsychotic serum concentration

6) carbamazepine

  • agranulocytosis w clozapine
49
Q

monitoring therapeutic outcomes for antipsychotics

A

1) Trial period

  • responsiveness
    ** compliance to adequate trial of at least 2-6 wks at optimal therapeutic dose
    ** clozapine need up to 3 months
  • adding another antipsychotic to clozapine
    ** augmentation trial of up to 8-10wks

2) monitoring effectiveness of therapy

  • MSE

3) monitoring AE

  • metabolic AE, MSE

4) ideal time course of treatment

  • early improvement
    ** 1st wk: decreased agitation, aggression, hostility
    ** 2-4 wks: decrease paranoia, hallucination, bizarre hallucination
  • late improvement
    ** 6-12 wks: decrease delusions
    ** 3-6months: improve cognitive symptoms (w SGA)
50
Q

adjunctive meds for acute agitation

A

1) cooperative patient

  • PO lorazepam
  • PO halo/risp/quet/olan

2) uncooperative and remain agitated/aggressive

  • fast acting IM injection for lorazepam/olanz/halo/promethazine or combinations lorazepam + halo or halo + promethazine
51
Q

adjunctive meds for catatonia

A

benzodiazepine (PO/IM Lorazepam)

52
Q

adjunctive meds for depressive symptoms or -ve symptoms of chronic Schizophrenia

A

treat with suitable antidepressants

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