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3153 IC9,10,11,12,14 Psychiatric > Schizophrenia > Flashcards

Schizophrenia Flashcards

1
Q

Onset of schizophrenia

A

Adolescent/early adulthood ~23.1y

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2
Q

Key clinical features of schizophrenia

A
  • Positive symptoms (e.g., delusions, hallucinations)
  • Negative symptoms (e.g., apathy, social isolation)
  • Functional impairment (cognitive symptoms)

*Negative symptoms become more dominant as disease progresses

Other associated symptoms may include:

  • Cognitive symptoms: impaired attention, impaired memory
  • Mood symptoms: depression, dysphoria, hopelessness, demoralization
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3
Q

Diagnoses with associated psychotic symptoms
*Need to rule out these diagnoses

A

Organic disorders:

  • Epilepsy
  • Cerebral lesions
  • Nervous system illness (infections, congenital)
  • Endocrine disorders (thyroid storm)
  • Metabolic disorders
  • Iatrogenic causes (drug-induced)
  • Alcohol
  • Psychoactive substance misuse
  • Parkinson’s disease (dopamine deficit)
  • Dementia

Affective disorders:

  • Mania
  • Psychotic depression
  • Post-partum psychosis

Schizophrenia:

  • Psychosis related to disorders of psychological development and/or to stress-related reactions
  • Psychotic symptom in context of adult personality disorder
  • Psychosis in childhood or adolescence
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4
Q

Pathophysiology of schizophrenia

A

Dysregulation of dopaminergic, serotonergic, and glutamatergic functions

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5
Q

Etiology of schizophrenia

A
  1. Predisposing
  • Genetics
  • Environment
  • Neurodevelopmental effects
  • Personality
  • Physical, psychological, and social factors in infancy and early childhood
  1. Precipitating
  • Cerebral tumors/injury
  • Drugs/substance-induced psychosis - rule out with urine toxicology
  • Misfortune
  • Emotions
  1. Perpetuating (prolongs the course of the disorder)
  • Poor adherence with antipsychotic medication
  • Social withdrawal
  • Lack of support
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6
Q

Example of what can cause drugs/substance-induced psychosis

A
  • Alcohol
  • Benzodiazepines
  • Barbiturates
  • Antidepressants
  • Systemic Corticosteroids (can cause anxiety, psychosis, depression)
  • CNS stimulants - amphetamines
  • Hallucinogens
  • Beta-blockers (e.g., propranolol)
  • Dopamine agonist (e.g., levodopa, bromocriptine)
  • Psychedelics (e.g., 5HT2A agonism)
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7
Q

Clinical Presentation (DSM-5 criteria for schizophrenia)

A

A. Two or more of the following, each persisting for at least a month:

  • Delusions
  • Hallucinations
  • Disorganized speech
  • Grossly disorganized or catatonic behavior
  • Negative symptoms (e.g., affective flattening, avolition, social isolation)

B. Social/occupational dysfunction

C. Duration: continuous signs of the disorder for at least 6 months

D. Schizoaffective or mood disorder has been excluded

E. Disorder is NOT due to medical disorder or substance use

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

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8
Q

General assessments

A
  • History of present illness
  • Psychiatric history – history neurosis (anxiety, depression etc.) or psychosis
  • Substance use – cigarettes, alcohol, substances
  • Complete medical history and medication history (Drug allergy? Other medications? Compliance?)
  • Family, social, forensic, developmental, and occupational history (1st-degree FH of illness, treatment, and response; review psychosocial circumstances every visit)
  • Physical and neurological exam (Injury? Esp head trauma?)
  • Mental state exam (Suicidal, homicidal ideations and risks; Reassess MSE every interview to evaluate efficacy and tolerability)
  • Labs and other investigations - Vital signs (BP, O2), weight, BMI, FBC, urea, electrolyte, creatinine, LFTs, TFTs, ECG, FBG, lipid panel, urine toxicology

E.g., ECG can check for QTc prolongation – affects choice of
drug

Exclude general medical conditions or substance-induced/withdrawal symptoms (e.g., psychosis, depression, mania, anxiety, insomnia)

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9
Q

Non-pharmaco management of psychosis

A
  1. Vocational training, psychosocial rehabilitation programs
  • improve pt’s adaptive function
  1. Individual cognitive behavioral therapy (CBT)
  • can be useful for : 1. preventing psychosis in ‘at risk’ groups - transient psychotic symptoms causing distress 2. first episode of psychosis 3. schizophrenia
  1. Neurostimulation - electroconvulsive therapy (ECT)
  • reserved for treatment-resistant schizophrenia, need to administer under generalized anesthesia

Others:
Neurostimulation - repetitive transcranial magnetic stimulation (rTMS) => may reduce auditory hallucinations

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10
Q

Goals of pharmacological treatment in schizophrenia

*3 phases, and goals within each phase

A
  1. Acute stabilization
  • Minimize threat to self and others
  • Minimize acute symptoms
  • Reduce agitation, aggression, hostility
  • Improve sleep
  1. Stabilization
  • Minimize/prevent relapse (note that with more relapse, it becomes more difficult to treat)
  • Promote med adherence
  • Optimize dose and manage adverse effects
  • Maintain baseline functioning
  1. Stable/maintenance phase
  • Improve functioning and QoL
  • Optimize dose
  • Monitor and manage adverse effects
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11
Q

Contrast antipsychotics (aka neuroleptics) with benzodiazepines

A

Antipsychotics:

  • Tranquilize without impairing consciousness and without causing paradoxical excitement
  • Treat psychosis symptoms
  • In the short-term, can be used to calm disturbed patients
  • In the long-term, for psychosis

Benzodiazepines:

  • Knocks patient out unconscious
  • Paradoxical excitement (agitation, aggression) when given to young patients or elderly or pt with head injury/trauma
  • Does not treat psychosis symptoms
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12
Q

Common indications of antipsychotics

A
  • Schizophrenia
  • Short-term adjunctive management of severe anxiety or psychomotor agitation, violent behavior
  • Acute mania
  • Adjunct with antidepressant for major depression (SGA: Quetiapine, Aripiprazole, Brexpiprazole)
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13
Q

Which antipsychotic can be used as antiemetic?

Motor tics and adjunctive tx in choreas and tourette’s

Intractable hiccups

Irritability a/w autism

A

Antiemetics:

  • Chlorpromazine
  • Haloperidol
  • Prochlorperazine

Motor tics and adjunctive tx in choreas and tourette’s

  • haloperidol

Intractable hiccups

  • haloperidol

Irritability a/w autism

  • risperidone
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14
Q

Goal of antipsychotics treatment in schizophrenia

A

Relieve symptoms of psychosis such as thought disorder, hallucinations, and delusions, and prevent relapse

  • less effective in apathetic withdrawn patients
  • patients with acute symptoms of schizophrenia generally respond better than those with chronic symptoms
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15
Q

Duration of antipsychotics treatment in schizophrenia

A

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

  • Life-long maintenance therapy
  • High risk of relapse if withdrawn inappropriately
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16
Q

When does relapse occur after antipsychotic withdrawal
Explain why

A

Relapse is not immediate, often delayed for several week after cessation of treatment

  • Because adipose tissues act as depot reservoir after chronic regular usage of antipsychotics
  • Antipsychotics mostly lipophilic, stored in fat cells and can diffuse back into bloodstream after treatment cessation
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17
Q

What are some methods to overcome poor treatment adherence in schizophrenia?

A
  • IM long-acting injection (e.g., IM Risperidone microspheres q2w, IM Haloperidol decanoate q4w)
  • Community psychiatric nurse - home visit, administer LAI
  • Patient and family education
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18
Q

Antipsychotic MOA

  • Main dopamine tract
A

D2 antagonist

  • Blockade of Dopamine receptors in the mesolimbic tract can control positive symptoms (e.g., delusions, hallucinations)
19
Q

Explain the side effects that arise due to antipsychotics action on the mesocortical tract

A

Dopamine blockade or hypofunction in this region results in negative symptoms

20
Q

Explain the side effects that arise due to antipsychotics action on the nigrostriatal tract

A

Extrapyramidal side effects (EPSE)

21
Q

Explain the side effects that arise due to antipsychotics action on the tuberoinfundibular tract (in anterior pituitary)

A

Hyperprolactinemia

  • Increase prolactin release
  • Gynaecomastia (in male)
  • Breast swelling, pain, lactation
  • Sexual dysfunction - reversible, can be treated
  • Decrease BMD - osteoporosis
22
Q

In summary, link the following receptors to their respective therapeutic effects or postulated side effects

  • D2 antagonism
  • 5-HT1A agonism
  • 5-HT2A antagonism
  • 5-HT2C antagonism
  • H1 antagonism
  • a1 antagonism
  • M1 antagonism
  • IKr antagonism
A

Therapeutic effects:

  • D2 antagonism: improve positive symptoms
  • 5-HT1A agonism: anxiolytic effects
  • 5-HT2A antagonism: antidepressant effects, improve negative symptoms

Postulated side effects:

  • D2 antagonism: EPSE, hyperprolactinemia
  • 5-HT2C antagonism: weight gain
  • H1 antagonism: sedation, weight gain
  • a1 antagonism: orthostatic hypotension, dizzy, reflex tachycardia, sedation
  • M1 antagonism: peripheral anticholinergic effects (constipation, dry mouth, urinary retention, delirium), memory dysfunction
  • IKr antagonism: QTc interval prolongation (pro-arrhythmic, sudden cardiac death)
23
Q

Compare therapeutic effects and postulated side effects of FGA and SGA

A

FGA:

  • Efficacy: improve positive symptoms via D2 antagonism at mesolimbic tract
  • ADRs: More EPSE than SGAs due to D2 antagonism in nigrostriatal tract, Increased prolactin secretion due to D2 antagonism in tuberoinfundibular tract

SGA:

  • Efficacy: improve positive symptoms via D2 antagonism at mesolimbic tract AND may improve negative symptoms via 5HT2A antagonism
  • ADRs: More metabolic side effects (weight gain esp in Clozapine and Olanzapine - CO)
24
Q

(IC9) Additional benefits of atypical antipsychotics:

A

More effective against negative symptoms postulated due to 5-HT2A antagonism

  • E.g., clozapine, olanzapine, risperidone

Better mood stabilization (used as adjunct to antidepressant for MDD) postulated due to 5HT1A agonism

  • E.g., Quetiapine, Aripiprazole, Brexpiprazole

(Forfeit)
Better at mood stabilization postulated due to antidepressant effect of 5-HT2A antagonism

  • E.g., clozapine, olanzapine, risperidone

Ameliorate cognitive dysfunction

  • E.g., clozapine, risperidone
25
Q

Explain the antipsychotic effect threshold

*Exceptions

A

Antipsychotic effect threshold < Prolactin threshold < EPS threshold

  • Only 60-80% D2 receptor blockade is required for antipsychotic effect, any more blockade will lead to more SEs

*Exceptions: Clozapine, Quetiapine - only 50-60% blockade required for antipsychotic effect

*Haloperidol is a very potent D2 antagonist (5mg => more than 80% D2 blockade)

26
Q

[Treatment algorithm for Schizophrenia]

Patient is diagnosed with schizophrenia, what drug to use first?

A

Single FGA or SGA (except Clozapine)

27
Q

[Treatment algorithm for Schizophrenia]

Patient has tried a single FGA/SGA, no/inadequate response, what to try next?

A

Try another single FGA or SGA (except Clozapine)

28
Q

[Treatment algorithm for Schizophrenia]

Patient has tried a single FGA/SGA twice, no/inadequate response, what to try next?

A

Clozapine

*Treatment-resistant schizophrenia (TRS):

  • Failed >= 2 adequate trials of diff antipsychotics (at least one must be SGA)
  • Treatment refractory evaluation should be performed to reexamine diagnosis, substance abuse, med adherence, psychosocial stressors
  • may need to consider CBT or psychosocial augmentation (e.g., rehabilitation)

Do not delay Clozapine, do not want to cause clozapine-resistance as there would be no other drug choice

29
Q

[Treatment algorithm for Schizophrenia]

Patient has tried Clozapine, still inadequate/no response, what next?

A

Clozapine + Augmenting agent

*Augmenting agent: FGA or SGA or ECT or other agents such as mood stabilizers

30
Q

[Treatment algorithm for Schizophrenia]

If treatment has adequate response and no intolerable side effects and patient is compliant, what should be done?

A

Continue treatment

31
Q

[Treatment algorithm for Schizophrenia]

If treatment has partial response, what should be done?

A
  • Increase dose if tolerable
  • Change drug if intolerable
32
Q

What is the duration of an adequate trial of antipsychotics?

A
  • At least 2-6 weeks at optimal therapeutic doses
  • Except Clozapine: 3 months to confirm therapeutic response
  • Adequate augmentation trial of up to 8-10 weeks required if another antipsychotic added to Clozapine
33
Q

What must be monitored when on Clozapine?

A

Mandatory routine hematological monitoring (monitor FBC)

  • due to risk of agranulocytosis

FYI: Clozapine has the best evidence in suicide prevention, however it is not first line due to risk of agranulocytosis

34
Q

Precautions to antipsychotic use

A
  • Cardiovascular disease

Contraindicated if QTc prolongation
ECG may be required if:
- physical exam identifies CVD risk factors
- if there is personal hx of CVD disease
- if pt is being admitted as inpatient and naive to antipsychotics)
Precaution if existing CVD such as HTN, post-MI, AF etc.
Refer to cardiologist if >500ms

  • Parkinson disease (EPSE worsened by antipsychotics, esp low-potency Clozapine or Chlorpromazine)
  • Epilepsy, seizures
  • Depression
  • Myasthenia gravis
  • Prostatic hypertrophy (anticholinergic effects)
  • Acute-closure glaucoma (anticholinergic effects)
  • Severe respiratory disease
  • History of jaundice
  • Blood dyscrasias - esp for Clozapine, possibly Chlorpromazine
  • Elderly with dementia (incr risk for stroke, CVD events, mortality)
35
Q

[Adjunctive Treatment]

  • Acute agitation (pt is cooperative)
A

If pt cooperative:

  • Oral Lorazepam 1-2mg
  • Oral antipsychotics: Haloperidol, Olanzapine, Risperidone, Quetiapine

*Haloperidol - require pre-treatment ECG
*May use combi

36
Q

[Adjunctive Treatment]

  • Acute agitation (pt is uncooperative)
A

If pt uncooperative, agitated/aggressive:
Restrain and administer fast-acting IM injection

  • IM Lorazepam 1-2mg
  • IM antipsychotics: Haloperidol, Olanzapine, Aripiprazole, Promethazine

*Why not IV - risk of blood pressure crash, cardiac arrest
*Promethazine - more for sedative properties of antihistamine, anticholinergic; avoid in infant <2yo due to sudden infant death
*Haloperidol - require pre-treatment ECG
*May use combi (e.g., Lorazepam + Haloperidol/Promethazine)

37
Q

[Adjunctive Treatment]

  • Acute agitation

IM _________ and IM _________ must not be given within __ of each other due to risk of ________

A

IM Olanzapine and IM Lorazepam must not be given within 1h of each other due to risk of cardiorespiratory fatality (excess sedation + respiratory depression)

https://www.aliem.com/combination-parenteral-olanzapine-benzodiazepines-agitation-adverse-events/#

38
Q

[Adjunctive Treatment]

  • Catatonia (disorganized thoughts)
A

Benzodiazepines: PO/IM Lorazepam

39
Q

[Adjunctive Treatment]

  • Depressive symptoms and/or negative symptoms of chronic schizophrenia
A

Depression: treat with suitable antidepressant
Negative symptoms: mild-mod efficacy with antidepressants e.g., SSRIs

40
Q

[PK of oral antipsychotics]

  • Most oral antipsychotics have Tmax 1-3h (rapidly absorbed, fast onset)
  • What are the exceptions?
A

Fast onset: Risperidone, Quetiapine, Haloperidol

  • can use to calm disturbed patient ASAP

Exceptions: Brexpiprazole, Olanzapine, Aripiprazole (~4-6h)

41
Q

[PK of oral antipsychotics]

  • Most oral antipsychotics have long t1/2, may be consolidated as once-daily dosing
  • What are the exceptions? - CCAQZ
  • What are the risks to consider when consolidating doses?
A

Exceptions: Chlorpromazine, Amisulpride, Clozapine, Quetiapine, Ziprasidone

These must be given in divided doses, due to risk of hypotension and seizures if consolidating doses

42
Q

[PK of oral antipsychotics]

Administration of Lurasidone/Ziprasidone

A

Administering Lurasidone/Ziprasidone with/after food may increase bioavailability

43
Q

[Dosing of oral antipsychotics]

High potency vs low potency antipsychotics

A

High potency:

  • Haloperidol 5-15mg per day
  • Risperidone 2-6mg per day
  • Olanzapine 5-20mg per day

Low potency:

  • Clozapine 200-450mg per day
  • Chlorpromazine 50-400mg per day
44
Q

[Dosing of IM long-acting antipsychotics]

A

Haloperidol decanoate - q4w

Risperidone - q2w (supplement with oral dose during 1st 3 weeks upon initiating 1st injection due to delayed onset of the injection)

Paliperidone - q3m

3153 IC9,10,11,12,14 Psychiatric (10 decks)

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