Schizophrenia Flashcards

1
Q

Schizophrenia sns

A

A) Two or more of the following, each persisting for a significant portion of at least a 1-month period:

(1) delusions
(2) hallucinations
(3) disorganized speech
(4) grossly disorganized or catatonic behavior
(5) negative symptoms
(e. g. Affective flattening, Alogia, Anhedonia, Avolition)

B) Social/occupational dysfunction
one or more major areas of functioning such as work

C)Continuous signs of the disorder for at least 6 months.
D. Schizoaffective or mood disorder has been EXCLUDED.
E. Disorder is NOT due to a medical disorder or substance use.

F. 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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2
Q

Non-Pharmacological Treatment

A

Individual Cognitive Behavioural Therapy (CBT)
– Used in conjunction with medications and family Intervention
- First Episode Psychosis: Assess for PTSD

Electroconvulsive Therapy (ECT) 
– Reserved for treatment-resistant Schizophrenia 

Repetitive Transcranial Magnetic Stimulation (rTMS) – Effective for reducing auditory hallucinations in Schizophrenia

Psychosocial rehabilitation programs:
- improving patient’s adaptive functioning

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3
Q
Electroconvulsive Therapy (ECT) 
– Reserved for treatment-resistant Schizophrenia
A
Electroconvulsive Therapy (ECT) 
– Reserved for treatment-resistant Schizophrenia
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4
Q

Effective for reducing auditory hallucinations in Schizophrenia

A

Repetitive Transcranial Magnetic Stimulation (rTMS) – Effective for reducing auditory hallucinations in Schizophrenia

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5
Q

Repetitive Transcranial Magnetic Stimulation (rTMS) –

A

Repetitive Transcranial Magnetic Stimulation (rTMS) – Effective for reducing auditory hallucinations in Schizophrenia

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6
Q

Pharmacological Treatment:

Establishing Therapeutic Goals

A
  1. Acute Stabilization
    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
  2. Stabilization
    a. Minimize/prevent relapse
    b. Promote medication adherence
    c. Optimize dose vs. adverse effects
  3. Stable/maintenance phase
    a. Improve functioning & quality of life
    b. Maintain baseline functioning
    c. Optimize dose vs. Adverse effects
    d. Monitor for prodromal Sx of Relapse
    e. Monitor for Adverse effects (e.g. Tardive Dyskinesia)
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7
Q

Pharmacological Treatment

Class
Function
Duration
when will Relapse

A

Antipsychotic Medications”
– Also known as “Neuroleptics”
• Generally tranquilize without impairing consciousness and without causing paradoxical excitement.

In the short term, they are used to calm disturbed patients whatever the underlying psychopathology which may be. • E.g. schizophrenia, mania, toxic delirium, or agitated depression.

Antipsychotics relieve symptoms of psychosis such as thought disorder, hallucinations and delusions, and prevent relapse.

  • Usually less effective in apathetic withdrawn patients.
  • Patients with acute symptoms of schizophrenia generally respond better than those with chronic
    symptoms.

Long-term treatment often necessary after the first episode of psychosis and prevent illness from becoming chronic.

may relapse if treatment is withdrawn inappropriately.
Relapse is often delayed for several weeks after cessation of treatment.
- Adipose tissues act as depot reservoir after chronic regular usage of antipsychotics.
– The antipsychotic (stored in fat cells) then diffuses back into blood stream after treatment cessation, until depletion

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8
Q

Methods to overcome poor treatment adherence

A

Methods to overcome poor treatment adherence
• Community Psychiatric Nurse
• IM long-acting injections
• Patient and Family (Caregiver) Education

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9
Q

Mechanism of Action - Antipsychotics

A

The central dopamine systems is composed of the following 4 tracts:
(1) Mesolimbic Tract: Blockade of the dopamine receptors in this tract is probably the common mechanism of action for all antipsychotics, because overactivity in this region is responsible for positive symptoms of Schizophrenia.

Blockade of the remaining 3 dopamine tracts causes adverse effects.

(2) Mesocortical (MC) Tract: This tract is responsible for higher-order thinking and executive functions. Dopamine blockade or hypofunction in this region results in negative symptoms.
(3) Nigrostriatal (NS) Tract: This tract modulates body movement. Antipsychotic-induced dopamine blockade in this region causes Extrapyramidal Side Effects (EPSE).
(4) Tuberoinfundibular (TI) Tract: Dopamine blockade in this region of the anterior pituitary leads to hyperprolactinemia.

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10
Q

D2 antagonism clinical implication

A

D2 Antagonism:
improve (+)ve Sx

causes EPSE, Hyperprolactinaemia

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11
Q

5-HT2A Antagonism:

clinical implication

A

5-HT2A Antagonism:
Antidepressant effects?
improve (-)ve Sx?

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12
Q

D2 receptor blockage %

A
60% = antipsychotic 
70% = prolactin threshold 
80% = EPS threshold
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13
Q

Algorithm for Schizophrenia

A

Use a single FGA or SGA (except Clozapine) –>
INADEQUATE OR NO RESPONSE (~4-6 weeks) –>
Use another single FGA or SGA (except Clozapine) not previously tried –>
INADEQUATE OR NO RESPONSE (~4-6 weeks) –>
Clozapine
–> Clozapine + Augmenting Agent (FGA or SGA or ECT)

OR
Clozapine
–> Refusal or Intolerable side effects –>
Combination Therapy e.g. Antipsychotic combinations (either FGA+FGA, or FGA+SGA), Antipsychotic + either ECT or other agent (e.g. mood stabilizer)

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14
Q

Algorithm for Schizophrenia – Important Footnotes

A
  1. Medication selection is INDIVIDUALISE for a patient, based on physician’s assessment of clinical circumstances, past response/failures on antipsychotics, patient needs, efficacy and side effect profiles of the therapy.
  2. Patients require COMPLIANCE to an adequate trial of antipsychotic (excluding Clozapine) of at LEAST 4-6 weeks at optimal THERAPEUTIC doses (300 – 1000mg/day of Chlorpromazine equivalence) before being CONSIDERED as “non-responders” to the medication (Clozapine requires more time, up to 3 months). An adequate augmentation trial of up to 8-10 weeks is required if another antipsychotic is added to Clozapine.
  3. Manage any intolerable ADRs accordingly or switch to more suitable alternatives
  4. Consider a DEPOT/long-acting injectable antipsychotic if inadequately compliant,
    - such as IM Risperidone microspheres, IM Paliperidone prolonged release suspension, IM Haloperidol decanoate or IM Fluphenazine decanoate, IM Flupenthixol Decanoate, IM Pipothiazine Palmitate.
  5. Consider Clozapine in those who are Treatment-Resistant, i.e. those had failed 2 adequate trials of different antipsychotics (at least 1 should be a SGA).

Routine hematological monitoring is required for patients on Clozapine. A treatment refractory evaluation should be performed to reexamine diagnosis, substance abuse, medication adherence, and psychosocial stressors.

Cognitive Behavioral Therapy or Psychosocial augmentation should be considered.

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15
Q

DEPOT/long-acting injectable antipsychotic

A
- such as 
IM Risperidone microspheres, 
IM Paliperidone prolonged release suspension, 
IM Haloperidol decanoate 
IM Fluphenazine decanoate, 
IM Flupenthixol Decanoate, 
IM Pipothiazine Palmitate.
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16
Q

Precautions to Antipsychotic use

A

– Cardiovascular disease
• QTc prolongation (contraindicated)
• ECG may be required if physical exam identifies cardiovascular risk factors, or if there is personal history of cardiovascular disease, or if patient is being admitted as inpatient.

– Parkinson’s disease
• May be exacerbated by antipsychotics

– Epilepsy And conditions predisposing to epilepsy

– Depression 
– Myasthenia gravis 
– Prostatic hypertrophy 
– Angle-closure glaucoma 
– Severe respiratory disease 
– History of jaundice 

– Blood dyscrasias, • especially for Clozapine

– Elderly with Dementia • Increased risks for mortality and stroke.

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17
Q

Adjunctive Treatments

Acute Agitation (Psychiatric Emergency)

A
If patient cooperative: 
• Consider Oral Medication 
(A) p.o. Lorazepam 1 – 2mg, or 
(B) p.o Haloperidol* (tab, solution) 2 – 5mg or 
(C) (A)+(B), or

(D) p.o. Risperidone (tab, orodispersible, solution) 1–2mg, or
(E) (A)+(D), or
(F) p.o. Olanzapine (tab, orodispersible) 5 – 10mg, or
(G) p.o. Quetiapine 50-100mg (tab)

If patient uncooperative and remains agitated/ aggressive:
• Consider fast-acting IM injection
(a) IM Lorazepam 1 – 2mg, or
(b) IM Haloperidol* 2.5 – 10mg (pre-treatment ECG recommended but can be impossible to do), or
(c) (a)+(b), or

(d) IM Promethazine 25-50mg, or
(e) (b)+d).

Note *Consider use of anticholinergic where appropriate

• IM Aripiprazole, IM Ziprasidone, IM Olanzapine or S/L Asenapine may be considered if available

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18
Q

Catatonia

A

– Benzodiazepines • po/IM Lorazepam

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19
Q

Management of Side Effects

EPSE Dystonia ~10%

A

EPSE Dystonia ~10%

  • Muscle spasms, e.g. oculogyric crisis, torticollis
  • Onset: within minutes (if IM/IV) or hrs (if p.o.)

Risk
High potency antipsychotics: (eg haloperidol), neuroleptic-naïve patients, young

management: 
IM anticholinergic (benztropine, diphenhydramine)
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20
Q

management of ADR

EPSE: Pseudo-parkinsonism ~20%

A

EPSE: Pseudo-parkinsonism ~20%

  • Tremors, rigidity, bradykinesia, bradyphrenia, salivation
  • Onset: days or weeks

Risk
- Elderly females, those with previous neurological damage (e.g. head injury, stroke)

Management

  • Decrease antipsychotic dose, or switch to SGA
  • Anticholinergics PRN, e.g benzhexol (aka trihexyphenidyl), benztropine.
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21
Q

EPSE: Akathisia ~25%

ADR MANAGEMENT

A

EPSE: Akathisia ~25%

  • Restlessness
  • Onset: hrs to weeks

Risk
- High-potency antipsychotics> Risp> Olan> Quet/Cloz

Management

  • DECREASE antipsychotic dose, or switch to SGA
  • Propranolol 20mg TDS (max 160mg/day)
  • Clonazepam (low dose) PRN
  • Anticholinergics generally unhelpful
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22
Q

EPSE: Tardive dyskinesia ~15-20%

management of SE

A

EPSE: Tardive dyskinesia ~15-20%

  • Orofacial movements (lip chewing, tongue protrusion), choreiform hand movements pelvic thrusting.
  • Onset: months/years to develop, 50% irreversible.

RISK

  • FGA > SGA
  • Those who develop acute EPSEs when initiated on FGA
  • 5% of patients per year of antipsychotic exposure
  • Worsen with anticholinergic drugs

Management

  • Discontinue any anticholinergics
  • DECREASE antipsychotic dose, or switch to SGA (Clozapine most effective)
  • Valbenzine 40-80mg/day
  • Tetrabenazine 25 – 200mg/day
  • Clonazepam or diazepam PRN
  • ? Vitamin E: 400 – 1600IU/day.
23
Q

Hyperprolactinaemia management

A

Hyperprolactinaemia

  • Galactorrhea
  • Amenorrhoea
  • DECREASE libido
  • Gynecomastia (males)

RISK
- FGAs, Pali > = Risp >other SGAs

Management

  • DECREASE FGA dose
  • Dopamine agonist (e.g. amantadine, bromocriptine)
  • Switch to Aripiprazole
24
Q

management Metabolic SE

A

Metabolic
-Weight gain (of >7% from baseline), Diabetes, increase
Lipids

RISK

  • High: Olan, Cloz
  • Moderate: CPZ, Quet, Risp
  • Low: Ari, Zip, Lura, Halo

Management

  • Lifestyle modification: diet, exercise
  • Treat diabetes (e.g. with metformin), hyperlipidaemia
  • Switch to lower risk agents
25
Q

ADR of antipsychotics

A

Dystonia
Pseudo-parkinsonism
Akathisia
Tardive dyskinesia

Hyperprolactinaemia
Metabolic

CVS = OH, QT

CNS = sedation, seizure, neuroeptic malignant syndrome (NMS)

Increase LFT

Retinopathy 
Rash
pigmentation 
photosensitive 
agranulocytosis (clozapine)
26
Q

Orthostatic hypotesion
management
risk

A

CPZ > Cloz > Risp

management: switch to lower risk agent eg
FGA : flupenthixol, sulpiride
SGA: Aripiprazole, olanzapine

27
Q

QT prolong

risk and management

A

Thio > CPZ

management, switch to low risk agent
eg olan, ris

28
Q

sedation

risk and management

A

CPZ, cloz > Quet

switch to lower risk agent
eg aripri

29
Q

seizure

risk and management

A

cloz, cpz > other sga

switch to high potency agent eg: halo

30
Q

NMS

risk and management

A

risk = high potency AP

management = IV dantrolene/oral dopamine agonist / supportive measure
switch to SGA

31
Q

monitoring of SE

BMI

A

BMI = weekly for 1st 6 weeks or q visit x 6mth
(monthly x 3 months for SGA) x 6mth

q3mth when stabilise

32
Q

monitoring SE FBG

A

3 months after initiating SGA then annually

33
Q

WBC and ANC monitoring

A

weekly for 1st 18 weeks then monthly.

34
Q

Monitoring of side effect

A
BMI
waist circumference
FBG
lipid panel 
plasma prolactin 
BP
EPSE exam 

WBC and ANC (clozapine)
ECG (ziprasidone)

35
Q

Pregnancy give ________

A

haloperidol

clozapine

36
Q

Breast feed give ________

A

Sulpiride

olanzapine

37
Q

Renal impairement give )___________

A

haloperidol

olanzapine

38
Q

liver impairement give _______________

A

haloperidol

sulpiride/amisulpride

39
Q

elderly: note

A

avoid drug with high propensity for A1 blockage or Anticholinergic SE
eg: ziprasidone, amisulpride, sulpride
start low go slow

40
Q

Benzodiazapines + Clozapine: DROP RR, DROP BP

A

Benzodiazapines + Clozapine: DROP RR, DROP BP

41
Q

Antihypertensives, Trazodone + antipsy

A

worsen hypotension

42
Q

Carbamazepine + Clozapine

A

Agranulocytosis

43
Q

CYP inducer VS CYP inhibitor

A

inducer decrease concentration of antipsy

inhibitor increase concentration of antipsy

44
Q

influcence by 1A2

A

Phenothiazines, Halo, Cloz, Olan, Zi

45
Q

influence by 2D6

A

Phenothiazines, Halo, Risp, Ari, Olan, Zuclopenthi

46
Q

influence by 3A4

A

Quet, Zip, Ari, Risp

47
Q

Time course of treatment response

A

Time course of treatment response
– Early improvements
• 1st week – decrease agitation, aggression, hostility
• 2-4 weeks – decrease paranoia, hallucinations, bizarre behaviours, – improved organization in thinking

Late improvements
• 6-12 weeks – decrease delusions, Negative Sxs may improve
• 3-6 months – Cognitive Sxs may improve (SGAs)

48
Q

CYP1A2 inducer

A

Rifampicin
Phenobarbitone
Phenytoin
Cigarette smoking

49
Q

CYP1A2 inhibitor

A
Fluoxamine
Quinolone
Macrolide
Isoniazid
Ketoconazole
50
Q

CYP2D6 inducer

A

Rifampicin
Phenobarbitone
Phenytoin
Carbamazepine

51
Q

CYP2D6 inhibitor

A

Fluoxetine
Paroxetine
Duloxetine

52
Q

CYP3A4 inducer

A

Barbiturates
Carbamazepine
Phenytoin

53
Q

CYP3A4 inhibitor

A
Fluvoxamine
Norfluoxetine
TCA
Imidazole
Isoniazid
Macrolide