Schizo Flashcards
What is the DSM-5 Criteria for Schizophrenia?
1) ≥ 2 symptoms, each persisting for a significant portion of at least 1 month period
* Positive Symptoms: (symptoms that normal person without schizophrenia also has, but just amplified in schizo patients)
o (1) Delusions
o (2) Hallucinations
o (3) Disorganized speech
o (4) Grossly disorganized or catatonic behavior
* (5) Negative symptoms (symptoms that normal person without schizophrenia also has, but just diminished or absent in schizo patients)
o i.e. Affective flattening (no emotion), Avolition (no interest)]
2) Social or occupational dysfunction
* For a significant portion of the time since onset of the disorder, one or more major areas of functioning such as work, interpersonal relations, or self-care are significantly below the level prior to onset.
3) Duration of symptoms ≥ 6 months continuously
* Inclusive of at least 1 month of symptoms fulfilling criterion A (unless successfully treated). This 6 months may include prodromal or residual symptoms.
4) Schizoaffective or mood disorder has been excluded.
5) Disorder is NOT due to a medical disorder or substance use
6) If a history of a pervasive developmental disorder is present, there must be symptoms of hallucinations or delusions present for at least 1 month.
(only 1st five are impt)
What are the 2 most important therapeutic goals for ACUTE stabilisation phase for Schizo?
- Minimize threat to self and others
- Minimize acute symptoms
Others:
* Improve role functioning
* Identify appropriate psychosocial interventions
* Collaborate with family and caregivers; Support for Carers
What are the treatment goals for the stabilisation phase? (3)
- Minimize/ prevent relapse -> the more relapses that occur, the more likely that the same treatment used before will not be useful
- Promote medication adherence
- Optimize dose and manage adverse effects
What is the most important goal of treatment for maintenance/ stable phase?
- Improve functioning & quality of life
Others:
* Maintain baseline functioning
* Optimize dose vs. Adverse effects
* Monitor for prodromal symptoms of Relapse
* Monitor and manage adverse effects
What are some methods to overcome poor adherence to antipsychotic therapies? (3)
1) IM long acting injections
2) Community Psychiatric Nurse -> home visit and administer long acting injection regularly
3) Patient and Family (Caregiver) Education
State the role of Antipsychotics in Schizo, whether treatment is long term/short term and whether relapse will be delayed with cessation (3)
o Antipsychotics relieve symptoms of psychosis such as thought disorder, hallucinations and delusions, and prevent relapse
o Long term treatment often necessary
o Relapse often delayed for several weeks after cessation of treatment (due to deposition of lipophilic drug into adipose tissue with chronic use)
State the effects of blocking each of the dopaminergic pathways:
a) Mesolimbic tract
b) Mesocortical tract
c) Nigrostriatal tract
d) Tuberoinfundular tract
a) Mesolimbic tract = decrease in positive symptoms of Schizo
b) Mesocortical tract = causes negative symptoms
c) Nigrostriatal tract = causes extrapyrimidal Side Effects
d) Tuberoinfundular tract = causes hyperprolactinemia
State the duration of an “adequate” trial of antipsychotic and state which drug is the exception to this duration and that drug’s duration for adequate trial
2-6 weeks at optimal therapeutic dose.
Exception is Clozapine and adequate trial of Clozapine is up to 3 months
State when Clozapine is considered to be used in Schizo
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).
State the DOC for Acute Agitation if Patient is cooperative
PO Lorazepam 1-2mg
State what to do for Acute Agitation if Patient is uncooperative
Restrain + IM Lorazepam 1-2mg
State alternative therapy for Acute Agitation if Patient is cooperative but Benzodiazepine cannot be used (4)
PO Risperidone 1-2mg
Also possible:
* Haloperidol* (tab, solution) 2-5mg with pre-treatment ECG (can be difficult to do)
* Quetiapine 50-100mg (tab, immediate release), or
* Olanzapine (tab, orodispersible) 5-10mg, or
State alternative therapy for Acute Agitation if Patient is uncooperative but Benzodiazepine cannot be used (4)
- IM Olanzapine (immediate release) 5-10mg; 2nd dose ≥2h after 1st dose; 3rd dose ≥ 4h after 2nd dose.
- IM Olanzapine and IM Lorazepam must not be given within 1h of each other (risk of cardiorespiratory fatality).
- IM Aripiprazole (immediate release) 9.75mg: less hypotensive than IM Olanzapine option
- IM Haloperidol* 2.5-10mg, with pre treatment ECG (but can be difficult to do), or
- IM Promethazine 25-50mg
What is DOC for Catatonia
PO/IM Benzodiazepine
What is the dosing range of PO Haloperidol?
5-15mg
What is the maximum daily dose of PO Clozapine?
900 mg (450mg BD)
What is maximum daily dose of PO Quetiapine?
800mg
What is dosing range of PO Risperidone?
6mg/day in 1-2 divided doses
Name the 3 PO antipsychotics you should NOT use if you want something that is fast acting (Tmax 1-3 hrs)
Olanzapine, Aripiprazole, Brexpiprazole
Name the antipsychotics that require divided dosing and state what needs to be considered if consolidating dose (2 most impt, 4 others)
Chlorpromazine and Clozapine
Risk of hypotension and seizures need to be considered if consolidating doses
Others: Sulpiride; Amisulpride, Quetiapine, Ziprasidone
Which 2nd Gen antipsychotics are MOST associated with metabolic side effects (weight GAIN, DM, Hyperlipid)? (2)
Clozapine and Olanzapine
State the general ADR trend of 1st Gen and 2nd Gen Antipsychotic
- 1st Gen Antipsychotics (Typical or Conventional Antipsychotics) have more extrapyramidal side effects (EPSE) and ↑ Prolactin more compared to 2nd Gen (Atypical Antipsychotics)
- 2nd Gen Antipsychotics have more metabolic side effects (mainly Clozapine and Olanzapine; those 2 associated with weight gain)
Which EPSE is worsened with Anticholinergic use?
Tardive dyskinesia
State how to manage the various EPSEs
a) Dystonia
b) Pseudo-parkinsonism
c) Akathisia
d) Tardive dyskinesia
Dystonia: IM anticholinergics (e.g benztropine 2mg, diphenhydramine)
Pseudo-parkinsons:
- PRN Anticholinergic (1st line)
- Switch to SGA or decrease dose
Akathisia:
- PRN low dose Clonazepam (1st line) and/or Propranolol 20mg TDS
- Switch to SGA or decrease dose
Tardive dyskinesia:
- Discontinue Anticholinergic (worsens TD; 1st line)
- Valbenazine 40-80mg/day (1st line)
- PRN Clonazepam
- Switch to SGA or decrease dose
Which SGAs are LEAST associated with metabolic side effects? (4)
Aripiprazole, Lurasidone, Brexpiprazole, Ziprasidone
State how to manage the metabolic side effects of Antipsychotics (3)
- Treat diabetes (e.g. with metformin), hyperlipidemia
- Switch to lower risk agents (e.g Aripiprazole, Lurasidone)
- Lifestyle modification: diet, exercise
State how to manage Neuroleptic Malignant Syndrome (NMS) (2)
- IV Dantrolene 50mg TDS (muscle relaxant), oral dopamine agonist (e.g. amantadine, bromocriptine), supportive measures.
- Switch to SGA
State which antipsychotic is most associated with hematological ADRs, and how to manage it
Agranulocytosis associated with Clozapine.
Discontinue if severe (WBC <3x10^9/L or ANC<1.5x10^9/L)
State how to manage Hyperprolactinemia ADR
Switch to Aripiprazole
Alts: Decr dose, use dopamine agonist (Amantadine, bromocriptine)
State the general monitoring parameters of antipsychotics and their frequency of monitoring (5)
1) BMI (q3 mths when dose stable)
2) HbA1c or Fasting blood sugar (q3 mth after SGA initiation, then annually)
3) Lipids [Low risk patients: q2-5 years; High risk patients: (3 months after initiating SGA), q6 months]
4) EPSE exam (weekly till dose stable, then q3-5mth for FGA, yearly for SGA)
5) Blood pressure (q3 mth after initiation of SGA, then annually)
State monitoring parameter specific to Clozapine and the frequency
WBC and ANC; weekly for 1st 18 wks then monthly
State special considerations when prescribing antipsychotics to elderly (3 impt)
1) Avoid drugs with high propensity for alpha 1 adrenergic blockade (orthostatic hypotension) or anticholinergic side effects (constipation, urinary retention, delirium);
2) start low go slow;
3) simplify regime;
4) avoid adverse interactions;
5) avoid long T ½ drugs
Which psychiatric drugs have the LEAST CYP interactions? (5)
Mirtazapine, Escitalopram, Venlafaxine, Desvenlafaxine, Vortioxetine
State the clinically significant DDIs for Antipsychotics in general, and those for Clozapine. (4,3)
1) CNS depressant
2) alpha-1 adrenergic blocker, dopamine blocker (e.g metoclopramide), antihistamine, antimuscarinic
3) antihypertensive (inc hypotension)
4) dopamine agonists (antagonistic effect)
5) CBZ and other drugs that cause agranulocytosis
6) CYP1A2 inhibitor/inducer
State examples of CYP1A2 inhibitors (3)
Macrolide, Fluvoxamine, FQs
State the time course of treatment response (early vs late improvements) and the clinical effects seen
Early
1 wk: decr agitation
2-4 wk: decr hallucination and paranoia
Late:
6-12wk: decr delusion
3-6mths: improve cognition
State the psychiatric drugs that are potent CYP2D6 inhibitors (3)
Buproprion, Fluoxetine, Paroxetine
Which CYP enzymes do Fluvoxamine inhibit?
CYP1A2, 2C19
State the MOA at which SGAs may help improve negative symptoms
5HT-2A antagonism
State examples of CYP1A2 inducers (4).
- Rifampicin
- Phenobarbital
- Phenytoin
- Cigarette smoke
State the symptoms of NMS (5)
- Muscle rigidity (lead pipe)
- High fever,
- Autonomic dysfunction (inc PR, labile BP, diaphoresis)
- Altered consciousness (confused etc)
- Inc CK (rhabdomyolysis)
Which antipsychotics are associated with the least side effects (e.g tremor, muscle stiffness, weight gain, DM)?
Aripiprazole and Brexpiprazole
Which FGA associated with the most weight gain?
Chlorpromazine (Perphenazine also)
Which Antipsychotic has best evidence in reducing suicidality in patients?
Clozapine
Which SGA has the most anticholinergic effect?
Clozapine
Dosing range of Olanzapine?
5-20mg/day
What is the most important counselling point regarding Clozapine ADR?
If get fever, cough, sore throat, go see doctor immediately
