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54 CNS > Schizophrenia > Flashcards

Schizophrenia Flashcards

1
Q

What is psychosis?

A
  • Acute & severe episode of mental condition
  • Being out of touch with reality
  • Lack of insight
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2
Q

Schizophrenia is one of the more common forms of ______?

A

Protracted psychosis

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3
Q

Schizophrenia represents ___ ?

A

Heterogenous syndrome of disorganised and bizarre thoughts, delusions, hallucinations, impaired psychosocial functioning

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4
Q

What forms do hallucinations come in?

A

Auditory
Visual
Tactile
Olfactory
Gustatory

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5
Q

Average age of onset

A

23.1 years old in SG

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6
Q

2 notable organic disorders with associated psychotic symptoms

A

Iatrogenic causes
Psychosis related to alcohol & psychoactive substance misuse

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7
Q

Risk factors of schizophrenia (predisposing)

A

Genetics
Environment in utero
Neurodevelopmental effects
Personality
Physical, pscyhological & social factors in infancy & early childhood

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8
Q

Risk factors of schizophrenia (precipitating)

A

Cerebral tumours or injury
Drugs/substance-induced psychosis***
Personal misfortune
Environment of high expressed emotion

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9
Q

Risk factors of schizophrenia (perpetuating)

A

Secondary demoralisation
Social withdrawal
Lack of support/poor SES or environment
Poor adherence with antipsychotic medications***

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10
Q

DSM-5 for schizophrenia (A)

A

2 or more (each persisting for significant portion of at least 1 month period)
1. delusions
2. hallucinations
3. disorganised speech
4. grossly disorganised or catatonic behaviour
5. negative symptoms (affective flattening, avolition)

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11
Q

DSM-5 for schizophrenia (B)

A

Social/occupational dysfunction

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12
Q

DSM-5 for schizophrenia (C)

A

Duration:
Continuous signs of disorder for at least 6 months (inclusive of at least 1 month of symptoms fulfilling criterion A)

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13
Q

DSM-5 for schizophrenia (D)

A

schizoaffective or mood disorder has been excluded

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14
Q

DSM-5 for schizophrenia (E)

A

Disorder is NOT due to medical disorder or substance use

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15
Q

DSM-5 for schizophrenia (F)

A

If a history of a pervasive developmental disorder is present, there must be symptoms of
hallucinations or delusions present for at least 1 month.

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16
Q

Assessments prior to diagnosis & treatment (1)

A

History of present illness

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17
Q

Assessments prior to diagnosis & treatment (2)

A

Psychiatric history - any history of neurosis or psychosis

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18
Q

Assessments prior to diagnosis & treatment (3)

A

Substance use history - any past/current use of cigarettes/ETOH/substance

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19
Q

Assessments prior to diagnosis & treatment (4)

A

Complete medical/medication history
Reassess medication adherence every visit

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20
Q

Assessments prior to diagnosis & treatment (5)

A

Family, social, forensic, developmental & occupational history - 1st degree family history of illness, treatment & response, psychosocial conditions

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21
Q

Assessments prior to diagnosis & treatment (6)

A

Physical & neurological exam - any injury?

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22
Q

Assessments prior to diagnosis & treatment (7)

A

Mental State Exam (MSE)
- Assess for suicidal/homicidal ideations & risks**
- Reassess MSE on every interview to evaluate efficacy & tolerability

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23
Q

Assessments prior to diagnosis & treatment (8)

A

Labs
Vital signs, weight/BMI, FBC, U/E/Cr, LFTs, TFTs, ECG, fast blood glucose, lipid panel, urine toxicology

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24
Q

Assessments prior to diagnosis & treatment (9)

A

Other investigations - to exclude general medical conditions or substance-induced/withdrawal (e.g. psychosis, depression, mania, anxiety, insomnia)

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25
Q

Non-pharmacological management (individual)

A

Supportive/counselling
Personal therapy
Social skills therapy
Vocational sheltered*: employment, rehabilitation

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26
Q

Non-pharmacological management (group)

A

Interactive/social

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27
Q

Non-pharmacological management (cognitive behavioural)

A

CBT
Compliance theory

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28
Q

What is individual CBT useful for?

A

Preventing psychosis in “at risk” group
1st episode psychosis (need to assess for PTSD0
Schizophrenia

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29
Q

Place in therapy: neurostimulation

A

Electroconvulsive Therapy (ECT) - reserved for treatment-resistant Schizophrenia
rTMS - may reduce auditory hallucinations

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30
Q

Place in therapy: psychosocial rehabilitation programmes

A

Improving patient’s adaptive functioning

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31
Q

What are the therapeutic goals in acute stabilisation?

A

a. Minimize threat to self and others**
b. Minimize acute symptoms**
c. Improve role functioning
d. Identify appropriate psychosocial interventions
e. Collaborate with family and caregivers; Support for Carers

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32
Q

What are the therapeutic goals in stabilisation phase?

A

a. Minimise/prevent relapse
b. Promote medication adherence
c. Optimise dose and manage AEs

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33
Q

What are the therapeutic goals for stable/maintenance phase?

A

a. Improving functioning and QOL
b. Maintain baseline functioning
c. Optimising dose vs AEs
d. Monitor for prodromal symptoms of relapse
e. Monitor and manage AEs

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34
Q

Functions of antipsychotics

A
  • Tranquillise without impairing consciousness & causing paradoxical excitement
  • Useful to calm disturbed patients in the ST
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35
Q

Common indications of antipsychotic

A
  1. Schizophrenia and related psychoses
  2. ST adjunctive management for severe anxiety or psychomotor agitation
  3. Acute mania
  4. Adjunct with antidepressant for major depression
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36
Q

How is antipsychotics useful for schizophrenia?

A
  1. Relieve symptoms such as thought disorder, hallucinations and delusions
  2. Prevent relapse
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37
Q

Duration of antipsychotics for schizophrenia

A

Long term treatment often necessary after 1st episode of psychosis, prevent illness from becoming chronic

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38
Q

Why is maintenance therapy important for schizophrenia?

A

High risk of relapse if antipsychotic treatment is withdrawn inappropriately

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39
Q

When will relapse happen after cessation of treatment?

A

Relapse often delayed for several weeks
- Adipose tissues act as depot reservoir after chronic regular usage of antipsychotics

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40
Q

How to overcome poor treatment adherence?

A
  1. IM long-acting injections
  2. Community psychiatric nurse - home visit and administer LAI regularly
  3. Patient and family (caregiver) education
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41
Q

Positive symptoms

A
  1. Suspiciousness
  2. Delusions
  3. Hallucinations
  4. Conceptual disorganisation
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42
Q

Negative symptoms

A
  1. Affective flattening (lack of response)
  2. Alogia (lack of conversation)
  3. Anhedonia (lack of pleasure)
  4. Avolition (lack of motivation0
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43
Q

What are the dopamine pathways of the brain?

A
  1. Mesolimbic tract
  2. Mesocortical (MC) tract
  3. Nigrostrital (NS) tract
  4. Tuberoinflundibular (TI) tract
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44
Q

What is the mesolimbic tract responsible for?

A

Reward and emotion

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45
Q

Which pathway is the most common MOA for all antipsychotics? Why?

A

Mesolimbic. Overactivity in this region is responsible for positive symptoms of schizophrenia.

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46
Q

What is the overall MOA of antipsychotics?

A

All antipsychotics are D2 antagonist! Blockade of dopamine receptors.

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47
Q

Neurochemical (dopamine, serotonin, glutamate) theory are primarily theories of _______.

A

Positive symptoms

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48
Q

What is the mesocortical (MC) tract responsible for?

A

Cognition (higher-order thinking) and attention

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49
Q

What is the nigrostriatal tract responsible for?

A

Extrapyramidal motor system - modulates body movement

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50
Q

What is the tuberoinfundibular tract responsible for?

A

Pathway from hypothalamus to anterior pituitary regulates prolactin secretion into blood circulation

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51
Q

What AEs do dopamine blockade in MC tract cause?

A

Dopamine blockade or hypo function results in NEGATIVE symptoms

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52
Q

What AEs do dopamine blockade in NS tract cause?

A

Extrapyramidal Side Effects (EPSE)

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53
Q

What AEs do dopamine blockade in TI tract cause?

A

Hyperprolactinemia (osteoporosis, sexual dysfunction etc)

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54
Q

Therapeutic effects of D2 receptor

A

Antagonism: improve positive symptoms

55
Q

Therapeutic effects of 5-HT1A receptor

A

Agonism: anxiolytic

56
Q

Therapeutic effects of 5-HT2A receptor

A

Antagonism: antidepressant effects? improve negative symptoms? antipsychotic effects?

57
Q

Postulated side effects of D2 receptor

A

Antagonism: EPSE, hyperprolactinemia

58
Q

Postulated side effects of 5-HT2C receptor

A

Antagonism: weight gain

59
Q

Postulated side effects of H1 receptors

A

Sedation/weight gain

60
Q

Postulated side effects of a1 receptor

A

Antagonism: orthostasis, sedation

61
Q

Postulated side effects of M1 receptor

A

Antagonism: memory dysfunction, peripheral anticholinergic effects

62
Q

Postulated side effects of IKr receptor

A

Antagonism: QTc interval prolongation (pro-arrhythmic)

63
Q

How is medication selection individualised?

A

Based on physician’s assessment of clinical circumstances, past response/failures on antipsychotics, patient’s needs, efficacy, SE profile

64
Q

When are patients considered “non-responder” to the medication?

A

Compliance to an adequate trial of antipsychotic (excluding Clozapine) of at least 2-6 weeks at optimal therapeutic doses

65
Q

Examples of LAIs

A

IM Risperidone microspheres
IM Paliperidone prolonged release suspension, IM Aripiprazole LA
IM Haloperidol decanoate
IM Flupenthixol decanoate
IM Zuclopenthixol decanoate

66
Q

When should Clozapine be considered? (has life threatening SEs)

A

Treatment-Resistant, i.e. those had failed
≥ 2 adequate trials of different antipsychotics (at least 1 should be a SGA)

67
Q

Monitoring in patients on Clozapine

A

Mandatory routine haematological monitoring

68
Q

List of first generation antipsychotics (FGA)

A

Chlorpromazine
Haloperidol
Sulpiride
Trifluoperazine

69
Q

Precautions to antipsychotic use (1)

A

CVD
- QTc prolongation (contraindicated)
- ECG required (CV risk factors/history of CVD, NAIVE patients)

70
Q

Precautions to antipsychotic use (2)

A

PD - EPSE worsened by antipsychotic

71
Q

Precautions to antipsychotic use (3)

A

Prostatic hypertrophy

72
Q

Precautions to antipsychotic use (4)

A

Angle-closure glaucoma

73
Q

Precautions to antipsychotic use (5)

A

Severe respiratory disease

74
Q

Precautions to antipsychotic use (6)

A

**Blood dycrasias, especially for Clozapine

75
Q

Precautions to antipsychotic use (7)

A

Elderly with dementia - increased mortality and stroke risks!!

76
Q

Adjunctive treatment for acute agitation (cooperative patient) (A)

A

Consider PO medication
PO Lorazepam** 1-2mg or

77
Q

Adjunctive treatment for acute agitation (uncooperative, agitated/aggresive patient) (A)

A

Consider fast-acting IM injection
IM Lorazepam 1 – 2mg

78
Q

Adjunctive treatment for acute agitation (cooperative patient) (B)

A

(B) Haloperidol (tab, solution) 2 – 5mg with pre-treatment ECG (can be difficult to do), or
- Risperidone* (tab, orodispersible, solution) 1–2mg, or
- Quetiapine 50-100mg (tab, immediate release), or
- Olanzapine (tab, orodispersible) 5 – 10mg, or

79
Q

Adjunctive treatment for acute agitation (uncooperative, agitated/aggressive patient) (B)

A

(b) IM Olanzapine* (immediate release) 5-10mg; 2nd dose ≥2h after 1st dose; 3rd dose ≥4 h after 2nd dose. IM Olanzapine and IM Lorazepam must not be given within 1h of each other (risk of cardiorespiratory fatality).

80
Q

Adjunctive treatment for acute agitation (uncooperative, agitated/aggressive patient) (C)

A

IM Aripiprazole (immediate-release) 9.75mg: less hypotensive than IM Olanzapine option

81
Q

Adjunctive treatment for acute agitation (uncooperative, agitated/aggressive patient) (D)

A

IM Haloperidol* 2.5 – 10mg, with pre-treatment ECG (but can be difficult to do), or

82
Q

Adjunctive treatment for acute agitation (uncooperative, agitated/aggressive patient) (E)

A

IM Promethazine* 25-50mg

83
Q

Examples of SGA

A

Olanzapine, risperidone, clozapine, quetiapine

84
Q

t1/2 of Haloperidol

A

12-36hr

85
Q

t1/2 of Olanzapine

A

21-54hr

86
Q

t1/2 of Risperidone

A

3-20hr

87
Q

Most of antipsychotics have Tmax _______.

A

1-3hrs (rapidly absorbed, fast onset)

88
Q

Oral antipsychotics with exception Tmax=1-3hrs

A

Brexipiprazole (4hr), Olanzapine (6hr), Risperidone (1hr)

89
Q

Most oral antipsychotics have ______ t1/2.

A

Long t1/2 - once daily dosing

90
Q

Oral antipsychotics that require divided dosing

A

Chlorpromazine
Sulpiride
Amisulpride
Clozapine
Quetiapine

91
Q

What must be considered if consolidating doses?

A

Risk of hypotension and seizure

92
Q

Administering __________/____________ with/after food may increase bioavailability

A

Lurasidone
Ziprasidone

93
Q

Dosing of haloperidol (adult)

A

Starting: 0.5-3mg BD or TDS or 3-5mg BD or TDS (severe)
Per day: 5-15mg (conversion for 2mg/mL oral solution: 10 drops = 1mg)

94
Q

Dosing of Clozapine (adult)

A

Max dose: 900mg

95
Q

Dosing of Olanzapine (adult)

A

Per day: 5-20mg

96
Q

Dosing of Quetiapine (adult)

A

Max dose: 800mg

97
Q

Dosing of Risperidone (adult)

A

Per day: 2-6mg (conversion for oral solution: 1mL=1mg)

98
Q

Dosing of Haloperidol LAI

A

IM 50-300mg/4w

99
Q

Dosing of Risperidone LAI

A

IM 25-37.5mg/2w

100
Q

Special instruction for Risperidone LAI

A

Supplement with oral dose during 1st 3 weeks upon initiating first injection

101
Q

Paliperidone (Invega Trinza) is injected IM 175-525mg every ___________.

A

3 months

102
Q

Which 2 SGAs have significant weight gain SE?

A

Clozapine
Olanzapine

103
Q

Management of dystonia (EPSE)

A

Risk: high potency antipsychotics
IM anticholinergic e.g. benztropine, diphenhydramine

104
Q

Management of pseudo-parkinsonism (EPSE)

A
  1. Decrease antipsychotic dose or switch to SGA
  2. Anticholinergic PRN
105
Q

Management of Akathisia (EPSE)

A
  1. Decrease antipsychotic dose or switch to SGA
  2. Clonazepam (low dose) PRN
  3. Propanolol 20mg TDS
    Anticholinergic generally unhelpful
106
Q

Management of tardive dyskinesia

A

50% irreversible
Risk: FGA>SGA, worsens with anticholinergic
1. Discontinue any anticholinergics
2. Decrease antipsychotic dose or switch to SGA
3. VMAT2: Valbenazine 40-80mg/day
4. Clonazepam PRM

107
Q

Management of hyperprolactinaemia

A

Switch to Aripiprazole

108
Q

Management of metabolic SEs

A

Risks: High - olanzapine, clozapine, Low - aripiprazole, lurasidone, ziprasidone, haloperido
1. Lifestyle modification
2. Treat diabetes, hyperlipidemia
3. Switch to lower risk agents

109
Q

CVS side effects

A

Orthostatic hypotension
QTc prolongation
VTE/PE

110
Q

Neuroleptic malignant syndrome (NMS)

A

Muscle rigidity, fever, autonomic dysfunction
(increase PR, labile BP, diaphoresis), altered
consciousness, increase CK

111
Q

Management of NMS

A
  1. IV Dantrolene 50mg TDS, oral dopamine agonist (e.g. amantadine, bromocriptine) supportive measures
  2. Switch to SGA
112
Q

Hematological SE

A

Decrease in WBC
Agranulocytosis: decrease in absolute neutrophil count CLOZAPINE!!!!

113
Q

Management of haematological SE

A

Discontinue antipsychotic if severe: WBC<3x109/L or ANC<1.5x109/L

114
Q

Monitoring of weight gain

A

BMI
- Weekly for 1st 6 weeks or every visit (at least monthly for 3 months for SGA) x 6 months
- Every 3 months when dose stabilised

115
Q

Monitoring of DM

A

FBG or HbA1c
- Low-risk patients: annually
- High-risk patients: 4 months after initiating new
antipsychotic (or 3 months after initiating SGA), then annually

116
Q

Monitoring of hyperlipidemia

A

Lipid panel

117
Q

Monitoring of BP

A

3 months after initiating SGA then annually

118
Q

EPSE Exam for rigidity, tremors, akathisia, tardive dyskinesia

A

-Weekly for 1st 2 weeks after initiation new antipsychotic or until dose stabilized
-Low-risk patients: FGA q6 months; SGA q12 months
-High-risk patients: FGA: q3 months; SGA q12 months

119
Q

Clozapine monitoring (MANDATORY!!!!!!!!)

A

WBC and ANC (leucopenia/agranulocytosis)
- Singapore: Weekly for first 18 weeks, then monthly

120
Q

Ziprasidone monitoring

A

ECG
- OTc prolongation

121
Q

Pregnancy

A

Olanzapine, Clozapine - watch for gestational diabetes

122
Q

What is suitable for breast feeding

A

Olanzapine or Quetiapine

123
Q

What is preferred for renal impairment

A

Oral Aripiprazole

124
Q

What should be avoided in breast feeding mothers?

A

Clozapine

125
Q

What should be avoided for renal impairment?

A

Sulpiride
Amisulpride

126
Q

Elderly

A
  • Avoid drugs with high propensity for a1-adrenergic blockade (orthostatic hypotension) or anticholinergic side effects (constipation,
    urinary retention, delirium)
  • Start low go slow
  • Simplify regime
  • Avoid adverse interactions
  • Avoid long T1⁄2 drugs
127
Q

Drugs with CNS depressant effects

A

Additive CNS effects

128
Q

Drugs with antimuscarinic, antihistaminic, α1-adrenergic blockade or dopamine blockade

A

Additive AEs

129
Q

Dopamine-augmenting agents

A

Mutual antagonism with antipsychotics

130
Q

CYP 1A2 Inhibitors

A

Fluvoxamine, Quinolones, Macrolides, Isoniazid, Ketoconazole

131
Q

Effects of CYP1A2 inhibitors

A

Increase Phenothiazines, Halo, Clozapine, Olan, Zip

132
Q

Carbamazepine

A

Agranulocytosis with clozapine

133
Q

Evaluation of treatment response (early)

A

1st week
– Reduce agitation, aggression, hostility
2-4 weeks
– Reduce paranoia, hallucinations, bizarre behaviours
– Improved organization in thinking

134
Q

Evaluation of treatment response (late)

A

6-12 weeks
– Reduce delusions, Negative Sx may improve
3-6 months
– Cognitive Sx may improve (with SGAs)

54 CNS (13 decks)

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