IC10 Schizophrenia Flashcards
In d/dx, what are some causes of organic (2) and affective disorders (2)
organic d/o - iatrogenic causes, psychosis related to alcohol or psychoactive substance misuse
affective d/o - mania, psychotic depression
What is the primary pathophysiology of schizophrenia?
Dysregulation of dopaminergic or serotonergic functions
What are the 3 key factors in schizophrenia?
Predisposing (genetic factors)
Precipitating (drugs or substance-induced psychosis)
Perpetuating (poor adherence)
What is the DSM-5 criteria for schizophrenia?
(total 6)
(first one: HDDCN)
- Two or more of the following (5) persisting for at least 1 month → hallucinations, disorganised speech, delusions, grossly disorganised or catatonic behaviour, negative symptoms (eg. affective flattening or avolition)
- Social or occupational dysfunction → work, interpersonal relations or self-care being significantly below level prior to onset
- Duration → continuous signs of disorder for at least 6 months
- EXCLUDE schizoaffective or mood disorders
- EXCLUDE disorder due to medical disorder or substance use
- If a history of pervasive developmental disorder is present, there must be symptoms of hallucinations or delusions present for at least 1 month
What are the non-pharmacological measures in schizophrenia? (3)
- CBT (gd for pts who can manage their own feelings)
- Neurostimulation (ECT, rTMS)
- Psychosocial rehab programmes (improve adaptive functioning)
What are the 3 phases in schizophrenia pharmacotherapy and their therapeutic goals?
- Acute stabilisation → minimise threat to self and others, minimise acute symptoms
- Stabilisation → prevent relapse, promote adherence and optimise dose
- Maintenance → improve function and quality of life
What are 3 methods to improve poor adherence?
- IM long-acting injections
- Community psychiatric nurse
- Patient and family (caregiver) education
What are antipsychotics used for in the short term?
calm down disturbed patients
What are the 4 tracts implicated in antipsychotics MOA?
mesolimbic, mesocortical, nigrostriatal, tuberoinfundibular
What is the importance of the mesolimbic tract in antipsychotics’ MOA
Blockade of the dopamine receptors in this tract is a common MOA for all antipsychotics as overactivity in this region is responsible for positive symptoms of schizophrenia
What is the importance of the mesocortical tract in antipsychotics’ MOA
Dopamine blockage or hypofunction in this region results in negative symptoms
What is the significance of the nigrostriatal tract in antipsychotics’ MOA
Dopamine blockage causes extrapyrimidal side effects (EPSE)
What is the significance of the tuberoinfundibular tract in antipsychotics’ MOA
Dopamine blockage causes hyperprolactinemia, leading to gynecomastia, sexual dysfunction and lactation
Which receptor antagonism effect of antipsychotics help with negative and positive symptoms respectively?
Positive - D2 antagonism
Negative - 5-HT(2A) (postulated)
What side effects does D2 antagonism result in?
EPSE, hyperprolactinemia
What drugs should be started on diagnosis, in first and second inadequate response?
At dx - FGA/SGA (not clozapine)
1st inadequate - another FGA/SGA (not clozapine)
2nd inadequate - clozapine (or clozapine + FGA/SGA)
When should clozapine be started?
compliance to at least 2 adequate trials of the antipsychotic (excluding clozapine) (at least 1 must be SGA) of at least 2-6 weeks at optimal therapeutic doses
When should LA-IM injections be used?
Patient preference or uncompliant patients? (usually IM decanoate drugs)
What is the most important precaution in antipsychotic use (contraindication)?
Cardiovascular disease → CI in QTc prolongation, ECG required especially if a physical examination identifies CV risk factors or if the patient has a personal history of CV disease
What are other precautions to look out for in antipsychotic use? (6)
PPASEB
- Parkinson’s disease (EPSE worsened by antipsychotics)
- Prostatic hypertrophy
- Angle-closure glaucoma
- Severe respiratory disease
- Elderly with dementia (black box warning)
- Blood dyscrasias (especially for cloazpine)
What adjunctive medication can be given for acute aggression?
If cooperative: PO lorazepam (or PO haloperidol, risperidone)
If non-cooperative: IM lorazepam (or IM haloperidol, olanzapine, promethazine)
If very uncooperative: IM lorazepam + haloperidol OR IM lorazepam + promethazine
What adjunctive medication can be given for catatonia (cannot relax)?
Benzodiazepines (like PO/IM lorazepam)
What adjunctive medication can be given for depression?
SSRI
What are the half-lives of haloperidol, olanzapine and risperidone?
haloperidol: 12-36h
olanzapine: 21-54h
risperidone: 3-20h
What is the dosing for haloperidol?
5-15mg
What is the dosing for olanzapine?
5-20mg
What is the dosing for risperidone?
2-6mg
What is the max dose for quetiapine?
Max 800mg
What is max dose for clozapine?
Max 900mg
How should LA-IM risperidone be given?
every 2 weeks, supplement with PO dose during first 3 weeks
How should LA-IM paliperidone be given?
every 3 months
What are most antipsychotic’s tmax and what are the exceptions?
1-3h
exceptions: aripiprazole, brexpiprazole, olanzapine
Most antipsychotics have long half-lives and can be dosed OD, what are the exceptions (shorter)?
clozapine and chlorpromazine
Which two SGAs are more likely to cause weight gain?
Clozapine and Olanzapine
What are the 4 side effects classified under EPSE?
dystonia (painful muscle contractions)
pseudoparkinsonism (tremors, ridigidity, bradykinesia)
akasthasia (restlessness)
tardive dyskinesia (orofacial movements)
How should dystonia be managed?
IM anticholinergics (benztropine)
How should pseudoparkinsonism be managed?
Decrease dose/switch to SGA
Give PRN anticholinergics
How should akasthasia be managed?
Decrease dose/switch to SGA
Give PRN clonazepam
How should tardive dyskinesia be managed?
Discontinue any anticholinergics
Decrease dose/switch to SGA
Give valbenazine or PRN clonazepam
What are sx of hyperprolactinemia and how should it be managed?
Amenorrhea, lactation, gynecomastia, especially with FGAs
Decrease the FGA dose or switch to aripiprazole
What are metabolic side effects and how should they be managed?
weight gain, diabetes, lipids
lifestyle modification, treat w metformin or switch to lower risk agents (aripiprazole and lurasidone)
What are cardiovascular side effects and how should they be managed?
Orthostatic hypotension
Switch to SGA, get up slowly from rest
What are CNS side effects and how should they be managed?
Neuroleptic malignant syndrome (NMS) (lead pipe rigidity, fever, increased CK)
Give IV dantrolene or PO dopamine agonist
Switch to SGA
What are hematologic side effects and how should they be managed?
Decreased WBC, agranulocytosis (esp w clozapine)
Discontinue drug if severe
What should be monitored for antipsychotic side effects? (6)
BMI, FBG, lipid panel, BP, EPSE exam, WBC/ANC
How often should BMI be assessed?
every 3 months
How often should FBG be assessed?
3 months after starting, then annually
How often should BP be assessed?
3 months after starting, then annually
How often should EPSE exam be conducted?
FGA q3/6 mths; SGA q12 mths
(depending on high/low risk pts)
How often should WBC and ANC be taken for patients on clozapine?
Weekly for the first 18 weeks then monthly
Which 2 types of drugs should the elderly avoid?
- Avoid drugs with high propensity for α1-adrenergic blockage (risk of orthostatic hypotension)
- Avoid drugs with high propensity for anticholinergic side effects (constipation, urinary retention, delirium)
Which CYP isoforms does fluvoxamine inhibit?
1A2 and 2C19
Which antipsychotics inhibit CYP2D6 (3)
fluoxetine, paroxetine, bupropion
Which 5 drugs result in fewer CYP interactions?
Mirtazapine (impt)
Escitalopram
Venlafaxine
Desvenlafaxine
Vortioxetine
Which drugs have clinically significant interactions with antipsychotics? (6)
- Drugs w CNS effects
- Drugs with blockages at muscarinic, H1, α1 or DA receptors
- DA-augmenting agents
- Antihypertensives
- CYP1A2 inhibitors (fluvoxamine, quinolones, macrolides)
- CBZ (risk of agranulocytosis w cloazpine)
