IC 11 - Schizophrenia Flashcards
What is the pathophysiology of schizophrenia?
Dysregulation of dopaminergic (DA), serotonergic (5HT) and glutamatergic functions
Name 1 precipitating factor involved in Schizophrenia.
Drugs-/substance
What is one perpetuating factor that prolong the course of disorder?
Poor adherence to antipsychotic medications
What are symptoms of schizophrenia?
≥ 2 of the following for least a 1 month:
1. delusions
2. hallucinations
3. disorganized speech
4. grossly disorganized or catatonic behavior
5. negative symptoms
How is schizophrenia diagnosed?
- Symptoms
- Social/occupational dysfunction
- Continuous signs of disorder for min. 6 months (inclusive of prodromal or residual symptoms)
- Exclusion of Schizoaffective or mood disorder
What is one of the assessment that should be done for accurate diagnosis of schizophrenia?
Mental state exam (assess for suicidal/ homicidal ideations and risks)
List 4 non-pharmacological management for schizophrenia.
- Individual: Vocational sheltered (sheltered: employment, rehabilitation)
- Individual Cognitive Behavioral Therapy (CBT)
- Neurostimulation - Electroconvulsive Therapy (ECT)
- Psychosocial rehabilitation programs
Electroconvulsive Therapy (ECT) reserved for ____________ Schizophrenia
treatment resistant
What is the purpose of antipsychotics for Schizophrenia?
Relieve symptoms of psychosis such as thought disorder, hallucinations and delusions, and prevent relapse
Antipsychotics are more useful for _____ schizophrenia.
acute
Why is relapse often delayed for several weeks after cessation of treatment of schizophrenia?
The antipsychotic are stored in fat cells. This allow them to diffuses back into blood stream after treatment cessation.
List three methods to overcome poor treatment adherence.
- IM long acting injections
- Community Psychiatric Nurse home visit and administer long acting injections regularly
- Patient and Family (Caregiver) Education
What is the primary use of antipsychotics in schizophrenia? Relate to MOA.
Blockade of the dopamine receptors in mesolimbic tract
What are the three undesirable effects that may occur when dopamine receptors in other tracts (except mesolimbic tract) of the central dopamine systems are blocked?
- Negative symptoms
- Extrapyramidal side effects
- Hyperprolactinemia
How can schizophrenia treatment be given?
- Single antipsychotic (first or second gen)
- If no response, use another single antipsychotic
- Clozapine if no response from 2
- Clozapine + FGA/SGA/Electroconvulsive therapy if no reponse from 3
What is the duration for adequate trial of antipsychotic (excluding clozapine)?
2 to 6 weeks at optimal therapeutic doses
What is the duration for adequate trial of clozapine?
up to 3 months
What is the drug that can be used for treatment resistant schizophrenia?
Clozapine
What is considered treatment resistant schizophrenia?
failed ≥ 2 adequate trials of different antipsychotics (at least 1 should be a SGA).
What is a mandatory routine monitoring that should be done for patients on clozapine?
Hematological monitoring (periodic FBC due to risks for agranulocytosis)
Who should use antipsychotic with caution?
- Cardiovascular diseases
- Parkinson’s disease
- Prostatic hypertrophy
- Angle-closure glaucoma
- Severe respiratory disease
- Blood dyscrasias (esp Clozapine)
- Elderly with dementia
In the event of acute agitation (emergency) and patient is cooperative, what are the two medications that can be used?
- Oral Lorazepam 1 2mg
- Risperidone (tab, oro-dispersible, solution) 1 2mg
In the event of acute agitation (emergency) and patient is uncooperative, what are the fast acting medications that can be used?
- IM Lorazepam 1-2mg
- IM Olanzapine
- IM Haloperidol 2.5-10mg, with pre treatment ECG
- IM Promethazine 25-50mg
What medication in the event of catatonia?
Benzodiazepines (i.e. PO/IM Lorazepam)
What is the Tmax of oral antipsychotics in general?
1 to 3 hours (except Brexpiprazole,
Olanzapine, Aripiprazole)
What are the oral antipsychotics that do not have long T1/2?
Chlorpromazine, Sulpiride; Amisulpride, Clozapine, Quetiapine, Ziprasidone
What are the two risks that should be considered if giving multiple dose of oral antipsychotics?
Hypotension and seizures
What are the four extrapyramidal side effects of antipsychotics?
- Dystonia
- Pseudo-parkinsonism
- Akathisia
- Tardive dyskinesia
What can cause dystonia in treatment of schizophrenia?
High potency antipsychotics
How to manage dystonia in treatment of schizophrenia?
IM anticholinergics e.g. benztropine, diphenhydramine
How to manage Pseudo parkinsonism in treatment of schizophrenia?
- Anticholinergics PRN (e.g. benzhexol, benztropine)
- Decrease antipsychotic dose, or switch to SGA
How to manage Akathisia in treatment of schizophrenia?
- Clonazepam (low dose) PRN and/or propranolol
- decrease antipsychotic dose, or switch to SGA
What are the risks for Tardive dyskinesia in treatment of schizophrenia?
- FGA > SGA
- Anticholinergic drugs (worsen)
How to manage Tardive dyskinesia in treatment of schizophrenia?
- Discontinue any anticholinergics
- Valbenazine 40 80mg/day
- Decrease antipsychotic dose, or switch to SGA
(Clozapine) - Clonazepam PRN
Tardive dyskinesia is 50% _______.
irreversible
How can hyperprolactinemia be managed?
Switch to Aripiprazole
List four drugs that may cause metabolic side effects such as weight gain, diabetes and hyperlipidemia.
- High risk - Olanzapine, Clozapine
- Low risk - Aripiprazole, Lurasidone
How to manage metabolic symptoms in schizophrenia patients?
- Switch to lower risk agents (Aripiprazole, Brexpiprazole, Cariprazine, Lurasidone)
- Treat diabetes (e.g. with metformin),
hyperlipidemia - Lifestyle modification: diet, exercise
What are the adjunctive treatments that can be given for agitation and depression in schizophrenia patients?
- Benzodiazepines (agitation)
- Antidepressants (for depression).
What is one cardiovascular side effect of antipsychotics?
Orthostatic hypotension
What is the main CNS side effect of antipsychotics?
Neuroleptic malignant syndrome (NMS): Muscle rigidity, fever, autonomic dysfunction (Increase PR, labile BP, diaphoresis), CK, altered consciousness.
How can Neuroleptic malignant syndrome (NMS) be managed in schizophrenia patients?
- IV Dantrolene 50mg TDS
- Oral dopamine agonist (e.g. amantadine, bromocriptine)
- Switch to SGA
How can hematological side effects caused by antipsychotics be managed?
Discontinue antipsychotic if severe : WBC<3x10^9 /L or ANC<1.5x10^9 /L
List the parameters that is required for monitoring of side effects.
- BMI (q3 months)
- Fasting blood sugar (3 months after SGA then annually)
- Lipid panel (3 months after SGA then annually)
- BP
- EPSE Exam
What parameters should be monitored for Clozapine?
WBC and ANC (Weekly for first 18 weeks , then monthly)
List 5 special population that require caution use of antipsychotics.
- Pregnancy
- Breast feeding
- Renal impairment
- Hepatic impairment
- Elderly
Which of the two antipsychotics can be used in pregnant women?
Olanzapine, Clozapine
What should be monitored for in pregnant women with schizophrenia?
Gestational diabetes
Which antipsychotics can breastfeeding mothers used?
Olanzapine or Quetiapine
Patients on _____ should not breastfeed.
Clozapine
Which antipsychotic can be used in renal impaired patients?
Oral Aripiprazole
Which antipsychotic is prefered in hepatic impaired patients when treating schizophrenia?
Sulpiride, Amisulpride
In the management of elderly with schizophrenia, what can be done?
- Simplify regime
- Avoid drugs with high propensity for α1 adrenergic blockade (orthostatic hypotension) or anticholinergic side effects
Which of the antipsychiatry drugs is an inhibitor of CYP1A2 and 2C19?
Fluvoxamine
Which antipsychiatry drugs are inhibitor of CYP2D6?
Bupropion, fluoxetine, paroxetine
Which food is an inhibitor of CYP3A4?
Grapefruit juice
Name one anti-psychiatric drug that has few CYP interactions.
Mirtazapine
Which of the ASM can cause increased agranulocytosis risk with Clozapine?
Carbamazepine
Name 3 drugs that can affect metabolism of clozapine.
CYP1A2 inhibitors: Fluvoxamine, Quinolones, Macrolides
What lifestyle condition can induce CYP1A2?
Smoking
What class of drugs can increase hypotensive risk when taken together with antipsychotic drugs?
Antihypertensive
Which agents may lead to mutual antagonism with antipsychotics?
Dopamine augmenting agents
Which of the drug can lead to additive adverse effects in antipsychotics?
- Antimuscarinic
- Antihistaminic,
- α-1 adrenergic blockade
- Dopamine blockade
Drugs with ____ _____ effects can increase CNS side effects.
CNS depressant
Effectiveness of therapy can be monitored via ______ side effects.
muscular
How can one monitor for adverse effects of anti-psychotics?
Metabolic parameters and EPSE
Response of anti-psychotics drugs can be seen in _____ weeks for those that responded early.
2 to 4
After 2 to 4 weeks, patients should have decreased ____ and _____.
paranoia, hallucinations
Late improvements in patients is usually seen in ______ weeks.
6 to 12
Which generation of the antipsychotics have more muscular related side effect?
First Generation
Which generation of the antipsychotics have more metabolic side effects?
Second generation (especially -apines)
- Exception: Aripiprazole, Brexpiprazole
Cariprazine, Lurasidone
For stabilization and maintenance phase, IM _____ antipsychotics such as IM Haloperidol Decanoate is preferred.
long acting