Schizophrenia Flashcards
1
Q
What is psychosis?
A
- Acute & severe episode of mental condition
- Being out of touch with reality
- Lack of insight
2
Q
Schizophrenia is one of the more common forms of ______?
A
Protracted psychosis
3
Q
Schizophrenia represents ___ ?
A
Heterogenous syndrome of disorganised and bizarre thoughts, delusions, hallucinations, impaired psychosocial functioning
4
Q
What forms do hallucinations come in?
A
Auditory
Visual
Tactile
Olfactory
Gustatory
5
Q
Average age of onset
A
23.1 years old in SG
6
Q
2 notable organic disorders with associated psychotic symptoms
A
Iatrogenic causes
Psychosis related to alcohol & psychoactive substance misuse
7
Q
Risk factors of schizophrenia (predisposing)
A
Genetics
Environment in utero
Neurodevelopmental effects
Personality
Physical, pscyhological & social factors in infancy & early childhood
8
Q
Risk factors of schizophrenia (precipitating)
A
Cerebral tumours or injury
Drugs/substance-induced psychosis***
Personal misfortune
Environment of high expressed emotion
9
Q
Risk factors of schizophrenia (perpetuating)
A
Secondary demoralisation
Social withdrawal
Lack of support/poor SES or environment
Poor adherence with antipsychotic medications***
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)
11
Q
DSM-5 for schizophrenia (B)
A
Social/occupational dysfunction
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)
13
Q
DSM-5 for schizophrenia (D)
A
schizoaffective or mood disorder has been excluded
14
Q
DSM-5 for schizophrenia (E)
A
Disorder is NOT due to medical disorder or substance use
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.
16
Q
Assessments prior to diagnosis & treatment (1)
A
History of present illness
17
Q
Assessments prior to diagnosis & treatment (2)
A
Psychiatric history - any history of neurosis or psychosis
18
Q
Assessments prior to diagnosis & treatment (3)
A
Substance use history - any past/current use of cigarettes/ETOH/substance
19
Q
Assessments prior to diagnosis & treatment (4)
A
Complete medical/medication history
Reassess medication adherence every visit
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
21
Q
Assessments prior to diagnosis & treatment (6)
A
Physical & neurological exam - any injury?
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
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
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)
25
Non-pharmacological management (individual)
Supportive/counselling
Personal therapy
Social skills therapy
Vocational sheltered*: employment, rehabilitation
26
Non-pharmacological management (group)
Interactive/social
27
Non-pharmacological management (cognitive behavioural)
CBT
Compliance theory
28
What is individual CBT useful for?
Preventing psychosis in "at risk" group
1st episode psychosis (need to assess for PTSD0
Schizophrenia
29
Place in therapy: neurostimulation
Electroconvulsive Therapy (ECT) - reserved for treatment-resistant Schizophrenia
rTMS - may reduce auditory hallucinations
30
Place in therapy: psychosocial rehabilitation programmes
Improving patient's adaptive functioning
31
What are the therapeutic goals in acute stabilisation?
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
32
What are the therapeutic goals in stabilisation phase?
a. Minimise/prevent relapse
b. Promote medication adherence
c. Optimise dose and manage AEs
33
What are the therapeutic goals for stable/maintenance phase?
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
34
Functions of antipsychotics
- Tranquillise without impairing consciousness & causing paradoxical excitement
- Useful to calm disturbed patients in the ST
35
Common indications of antipsychotic
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
36
How is antipsychotics useful for schizophrenia?
1. Relieve symptoms such as thought disorder, hallucinations and delusions
2. Prevent relapse
37
Duration of antipsychotics for schizophrenia
Long term treatment often necessary after 1st episode of psychosis, prevent illness from becoming chronic
38
Why is maintenance therapy important for schizophrenia?
High risk of relapse if antipsychotic treatment is withdrawn inappropriately
39
When will relapse happen after cessation of treatment?
Relapse often delayed for several weeks
- Adipose tissues act as depot reservoir after chronic regular usage of antipsychotics
40
How to overcome poor treatment adherence?
1. IM long-acting injections
2. Community psychiatric nurse - home visit and administer LAI regularly
3. Patient and family (caregiver) education
41
Positive symptoms
1. Suspiciousness
2. Delusions
3. Hallucinations
4. Conceptual disorganisation
42
Negative symptoms
1. Affective flattening (lack of response)
2. Alogia (lack of conversation)
3. Anhedonia (lack of pleasure)
4. Avolition (lack of motivation0
43
What are the dopamine pathways of the brain?
1. Mesolimbic tract
2. Mesocortical (MC) tract
3. Nigrostrital (NS) tract
4. Tuberoinflundibular (TI) tract
44
What is the mesolimbic tract responsible for?
Reward and emotion
45
Which pathway is the most common MOA for all antipsychotics? Why?
Mesolimbic. Overactivity in this region is responsible for positive symptoms of schizophrenia.
46
What is the overall MOA of antipsychotics?
All antipsychotics are D2 antagonist! Blockade of dopamine receptors.
47
Neurochemical (dopamine, serotonin, glutamate) theory are primarily theories of _______.
Positive symptoms
48
What is the mesocortical (MC) tract responsible for?
Cognition (higher-order thinking) and attention
49
What is the nigrostriatal tract responsible for?
Extrapyramidal motor system - modulates body movement
50
What is the tuberoinfundibular tract responsible for?
Pathway from hypothalamus to anterior pituitary regulates prolactin secretion into blood circulation
51
What AEs do dopamine blockade in MC tract cause?
Dopamine blockade or hypo function results in NEGATIVE symptoms
52
What AEs do dopamine blockade in NS tract cause?
Extrapyramidal Side Effects (EPSE)
53
What AEs do dopamine blockade in TI tract cause?
Hyperprolactinemia (osteoporosis, sexual dysfunction etc)
54
Therapeutic effects of D2 receptor
Antagonism: improve positive symptoms
55
Therapeutic effects of 5-HT1A receptor
Agonism: anxiolytic
56
Therapeutic effects of 5-HT2A receptor
Antagonism: antidepressant effects? improve negative symptoms? antipsychotic effects?
57
Postulated side effects of D2 receptor
Antagonism: EPSE, hyperprolactinemia
58
Postulated side effects of 5-HT2C receptor
Antagonism: weight gain
59
Postulated side effects of H1 receptors
Sedation/weight gain
60
Postulated side effects of a1 receptor
Antagonism: orthostasis, sedation
61
Postulated side effects of M1 receptor
Antagonism: memory dysfunction, peripheral anticholinergic effects
62
Postulated side effects of IKr receptor
Antagonism: QTc interval prolongation (pro-arrhythmic)
63
How is medication selection individualised?
Based on physician's assessment of clinical circumstances, past response/failures on antipsychotics, patient's needs, efficacy, SE profile
64
When are patients considered "non-responder" to the medication?
Compliance to an adequate trial of antipsychotic (excluding Clozapine) of at least 2-6 weeks at optimal therapeutic doses
65
Examples of LAIs
IM Risperidone microspheres
IM Paliperidone prolonged release suspension, IM Aripiprazole LA
IM Haloperidol decanoate
IM Flupenthixol decanoate
IM Zuclopenthixol decanoate
66
When should Clozapine be considered? (has life threatening SEs)
Treatment-Resistant, i.e. those had failed
≥ 2 adequate trials of different antipsychotics (at least 1 should be a SGA)
67
Monitoring in patients on Clozapine
Mandatory routine haematological monitoring
68
List of first generation antipsychotics (FGA)
Chlorpromazine
Haloperidol
Sulpiride
Trifluoperazine
69
Precautions to antipsychotic use (1)
CVD
- QTc prolongation (contraindicated)
- ECG required (CV risk factors/history of CVD, NAIVE patients)
70
Precautions to antipsychotic use (2)
PD - EPSE worsened by antipsychotic
71
Precautions to antipsychotic use (3)
Prostatic hypertrophy
72
Precautions to antipsychotic use (4)
Angle-closure glaucoma
73
Precautions to antipsychotic use (5)
Severe respiratory disease
74
Precautions to antipsychotic use (6)
**Blood dycrasias, especially for Clozapine
75
Precautions to antipsychotic use (7)
Elderly with dementia - increased mortality and stroke risks!!
76
Adjunctive treatment for acute agitation (cooperative patient) (A)
Consider PO medication
PO Lorazepam** 1-2mg or
77
Adjunctive treatment for acute agitation (uncooperative, agitated/aggresive patient) (A)
Consider fast-acting IM injection
IM Lorazepam 1 – 2mg
78
Adjunctive treatment for acute agitation (cooperative patient) (B)
(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
Adjunctive treatment for acute agitation (uncooperative, agitated/aggressive patient) (B)
(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
Adjunctive treatment for acute agitation (uncooperative, agitated/aggressive patient) (C)
IM Aripiprazole (immediate-release) 9.75mg: less hypotensive than IM Olanzapine option
81
Adjunctive treatment for acute agitation (uncooperative, agitated/aggressive patient) (D)
IM Haloperidol* 2.5 – 10mg, with pre-treatment ECG (but can be difficult to do), or
82
Adjunctive treatment for acute agitation (uncooperative, agitated/aggressive patient) (E)
IM Promethazine* 25-50mg
83
Examples of SGA
Olanzapine, risperidone, clozapine, quetiapine
84
t1/2 of Haloperidol
12-36hr
85
t1/2 of Olanzapine
21-54hr
86
t1/2 of Risperidone
3-20hr
87
Most of antipsychotics have Tmax _______.
1-3hrs (rapidly absorbed, fast onset)
88
Oral antipsychotics with exception Tmax=1-3hrs
Brexipiprazole (4hr), Olanzapine (6hr), Risperidone (1hr)
89
Most oral antipsychotics have ______ t1/2.
Long t1/2 - once daily dosing
90
Oral antipsychotics that require divided dosing
Chlorpromazine
Sulpiride
Amisulpride
Clozapine
Quetiapine
91
What must be considered if consolidating doses?
Risk of hypotension and seizure
92
Administering __________/____________ with/after food may increase bioavailability
Lurasidone
Ziprasidone
93
Dosing of haloperidol (adult)
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
Dosing of Clozapine (adult)
Max dose: 900mg
95
Dosing of Olanzapine (adult)
Per day: 5-20mg
96
Dosing of Quetiapine (adult)
Max dose: 800mg
97
Dosing of Risperidone (adult)
Per day: 2-6mg (conversion for oral solution: 1mL=1mg)
98
Dosing of Haloperidol LAI
IM 50-300mg/4w
99
Dosing of Risperidone LAI
IM 25-37.5mg/2w
100
Special instruction for Risperidone LAI
Supplement with oral dose during 1st 3 weeks upon initiating first injection
101
Paliperidone (Invega Trinza) is injected IM 175-525mg every ___________.
3 months
102
Which 2 SGAs have significant weight gain SE?
Clozapine
Olanzapine
103
Management of dystonia (EPSE)
Risk: high potency antipsychotics
IM anticholinergic e.g. benztropine, diphenhydramine
104
Management of pseudo-parkinsonism (EPSE)
1. Decrease antipsychotic dose or switch to SGA
2. Anticholinergic PRN
105
Management of Akathisia (EPSE)
1. Decrease antipsychotic dose or switch to SGA
2. Clonazepam (low dose) PRN
3. Propanolol 20mg TDS
Anticholinergic generally unhelpful
106
Management of tardive dyskinesia
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
Management of hyperprolactinaemia
Switch to Aripiprazole
108
Management of metabolic SEs
Risks: High - olanzapine, clozapine, Low - aripiprazole, lurasidone, ziprasidone, haloperido
1. Lifestyle modification
2. Treat diabetes, hyperlipidemia
3. Switch to lower risk agents
109
CVS side effects
Orthostatic hypotension
QTc prolongation
VTE/PE
110
Neuroleptic malignant syndrome (NMS)
Muscle rigidity, fever, autonomic dysfunction
(increase PR, labile BP, diaphoresis), altered
consciousness, increase CK
111
Management of NMS
1. IV Dantrolene 50mg TDS, oral dopamine agonist (e.g. amantadine, bromocriptine) supportive measures
2. Switch to SGA
112
Hematological SE
Decrease in WBC
Agranulocytosis: decrease in absolute neutrophil count CLOZAPINE!!!!
113
Management of haematological SE
Discontinue antipsychotic if severe: WBC<3x109/L or ANC<1.5x109/L
114
Monitoring of weight gain
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
Monitoring of DM
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
Monitoring of hyperlipidemia
Lipid panel
117
Monitoring of BP
3 months after initiating SGA then annually
118
EPSE Exam for rigidity, tremors, akathisia, tardive dyskinesia
-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
Clozapine monitoring (MANDATORY!!!!!!!!)
WBC and ANC (leucopenia/agranulocytosis)
- Singapore: Weekly for first 18 weeks, then monthly
120
Ziprasidone monitoring
ECG
- OTc prolongation
121
Pregnancy
Olanzapine, Clozapine - watch for gestational diabetes
122
What is suitable for breast feeding
Olanzapine or Quetiapine
123
What is preferred for renal impairment
Oral Aripiprazole
124
What should be avoided in breast feeding mothers?
Clozapine
125
What should be avoided for renal impairment?
Sulpiride
Amisulpride
126
Elderly
- 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
Drugs with CNS depressant effects
Additive CNS effects
128
Drugs with antimuscarinic, antihistaminic, α1-adrenergic blockade or dopamine blockade
Additive AEs
129
Dopamine-augmenting agents
Mutual antagonism with antipsychotics
130
CYP 1A2 Inhibitors
Fluvoxamine, Quinolones, Macrolides, Isoniazid, Ketoconazole
131
Effects of CYP1A2 inhibitors
Increase Phenothiazines, Halo, Clozapine, Olan, Zip
132
Carbamazepine
Agranulocytosis with clozapine
133
Evaluation of treatment response (early)
1st week
– Reduce agitation, aggression, hostility
2-4 weeks
– Reduce paranoia, hallucinations, bizarre behaviours
– Improved organization in thinking
134
Evaluation of treatment response (late)
6-12 weeks
– Reduce delusions, Negative Sx may improve
3-6 months
– Cognitive Sx may improve (with SGAs)
