Antipsychotics Flashcards
Schizophrenia
What are the drug classes for Schizophrenia and their MOA?
Dopamine Receptor Antagonist
1. Typical Antipsychotic (D2)
2. Atypical Antipsychotic (D2, 5HT2A)
3. Benzodiazepines (GABA)
What are the goals of therapy for Schizophrenia?
Acute Stabilization
1. Reduce harm to self or others
2. Reduce symptoms
Stabilization and Maintenance
1. Relapse prevention
2. Adherence
3. QOL
What is the role of antipsychotics?
Calm down disturbed patients (Short-term tranquilizing effect without losing consciousness)
What are the 4 dopaminergic pathways in the brain?
- Mesolimbic (Reward): Positive Sx
- Mesocortical (Cognition): Negative Sx
- Nigrostriatal (Motor): EPSE
- Tuberoinfundibular (Milk): Prolactin
What are the postulated effects related to the neurotransmitters?
- D2: Positive Sx, EPSE, Prolactin
- 5HT2A: Negative Sx
- H1: Sedation, weight gain
- Alpha: Lightheadedness
- M1: Dry mouth, constipation, urinary retention
- IKr: QTc prolongation
What are the postulated effects related to different serotonin types?
5HT1A: Anxiety reduction
5HT2A: Depression reduction
5HT2C: Weight gain, appetite
5HT3: Nausea, vomiting
What is the criteria for adequate trial of antipsychotic in schizophrenia?
Optimal dose + 2 to 6 weeks duration
What is the criteria for treatment resistant schizophrenia?
Failed 2 or more adequate trials of antipsychotics (including at least one SGA)
What are the treatment options and dosing for acute agitation (psychiatric emergency) if the patient is compliant to medicine?
Either of these options:
(A) Oral Lorazepam 1 – 2mg
(B) Oral Antipsychotic:
- Haloperidol 2 – 5mg tablet/solution with pre-treatment ECG
- Risperidone 1–2mg tablet/ODT/solution
- Quetiapine 50-100mg Tablet/IR
- Olanzapine 5 – 10mg Tablet/ODT
What are the treatment options and dosing for acute agitation (psychiatric emergency) if the patient is NOT compliant to medicine?
Either of these options:
(a) IM Lorazepam 1 – 2mg
(b) IM Olanzapine 5-10mg; 2nd dose ≥2h after 1st dose; 3rd dose ≥4 h after 2nd dose.
(c) IM Aripiprazole 9.75mg
(d) IM Haloperidol 2.5 – 10mg, with pre-treatment ECG
(e) IM Promethazine 25-50mg
(f) (a) + (d)
(g) (d) + (e)
Why is it that IM Olanzapine and IM Lorazepam must not be given within 1h of each other?
Risk of cardiorespiratory fatality
Compare IM Aripiprazole with IM Olanzapine. Why will I choose one over another?
IM Aripiprazole less hypotensive than IM Olanzapine option
What can be used for catatonia during psychiatric emergency?
PO/IM Lorazepam 1-2 mg
Which antipsychotics can be consolidated as once-daily dosing and why?
Chlorpromazine, Sulpiride; Amisulpride, Clozapine, Quetiapine
Long half-life. Need to consider the risk of hypotension and seizures when consolidating doses!
What is the course of treatment response to antipsychotics?
Early Improvement
Week 1: Agitation, aggression and hostility reduced
Week 2-4: Paranoia, hallucinations reduced, thought organization
Late Improvement
Week 6-12: Delusions reduced, negative symptoms improve
Month 3-6: Cognitive symptoms improve (with SGA)
List the four types of EPSE and in layman terms
Dystonia: Muscle spasm and stiffness in the face, neck, back
Pseudo-parkinsonism: Uncontrollable shaking of limbs
Akathisia: Restlessness and need to keep moving constantly
Tardive dyskinesia: Smacking lips, moving of jaws and tongue
List the treatment and prophylaxis options for Dystonia EPSE
Benztropine 1-2 mg (Max: 6 mg/day)
- Initial: IM (once)
- Subsequent: PO BD to TDS
OR
Diphenhydramine 25-50 mg (Max: 300 mg/day)
- Initial: IM (once)
- Subsequent: PO q4-12h
List the treatment and prophylaxis options for Pseudo-parkinsonism EPSE
Trihexyphenidyl 1 mg/day (Range PO 5-15 mg/day)
List the treatment and prophylaxis options for Akathisia EPSE
PO Clonazepam 0.5 mg/day; increase daily dose based on response and tolerability by 0.5 mg every 5 days up to 4 mg/day in 2 divided doses
PO Propranolol 10 mg BD (Max: 120 mg/day)
List the treatment and prophylaxis options for Tardive Dyskinesia EPSE
None. Discontinue any anticholinergics, reduce the dose of antipsychotics
List of Typical Antipsychotics (D2 Neuroleptics) in NUH
- Haloperidol (0.5 mg green, 1.5 mg white, 5 mg pink)
- Chlorpromazine HCL (Largo, White tablet)
- Trifluoperazine (Stilizan, Blue tablet)
- Sulpiride (Devodil, White tablet)
Haloperidol: Formulations available, usual dose range for schizophrenia and max dosing?
Formulations
- 1.5 mg, 5 mg Tablet
- 2 mg/mL Oral Solution
- 5 mg/mL Injection
Max dosing varies per indication.
Usual Dose Range:
PO 3-5 mg BD (5-15 mg/day)
IM 2-10 mg per dose
Absolute max dosing: 100 mg/day, but doses >30 mg/day are in general not recommended
Chlorpromazine: Formulations available, usual dose range for schizophrenia and max dosing?
Formulations:
- 25 mg, 100 mg Tablet
- 50 mg IJ* EX
Max dosing varies per indication.
Usual Dose Range:
PO 25 mg BD (50-400 mg/day)
Absolute Max dosing: 800 mg/day
Trifluoperazine HCL: Formulations available, usual dose range for schizophrenia and max dosing?
Formulation: 5 mg Tablet
Usual Dose Range: 2-20 mg
Max dosing: 40 mg/day
Sulpiride: Formulations available, usual dose range for schizophrenia and max dosing?
Formulation: 200 mg Tablet
Depends on +/- Sx
Higher dose for +: 800 mg/day
Lower dose for -: 200 mg/day
Max dosing: 2400 mg/day
List of Atypical Antipsychotics (D2 and 5HT2 Neuroleptic)
More metabolic side effects
1. Quetiapine
2. Olanzapine
3. Clozapine
Less metabolic side effects
1. Risperidone (Eperon)
2. Paliperidone (Metabolite of risperidone) (Invega)
3. Aripiprazole
4. Brexpiprazole
5. Amisulpride
Quetiapine: Formulations available, usual dose range for schizophrenia and max dosing?
Formulation:
- IR Tab: 25mg, 100mg, 200mg
- XR Tab: 50mg, 200mg, 300mg
Usual Dose Range: 150-500 mg
Max dosing varies for indications.
Absolute max dosing: 800 mg/day
Olanzapine: Formulations available, usual dose range for schizophrenia and max dosing?
Formulations:
- 10 mg Orodispersible Tablet
- 5 mg, 10 mg Tablet
Usual Dose Range: 5-20 mg
Max: 20 mg/day
Risperidone: Formulations available, usual dose range for schizophrenia and max dosing?
Formulations:
- 1mg, 2mg Tablet
- 1mg/mL Oral Solution
Usual Dose Range: 2-6 mg
Max: 16 mg
Paliperidone: Formulations available, usual dose range for schizophrenia and max dosing?
Formulations:
- ER Tab: 3mg, 6mg, 9mg
- PR Injection: 50 mg to 525 mg
Max: 12 mg/day
Initial: 6 mg/day
Usual Dose Range: 3-12 mg
CrCL < 80 mL/min require dose adjustment (80% urinary excretion)
Aripiprazole: Formulations available, usual dose range for schizophrenia and max dosing?
Formulation
- 5 mg, 10 mg, 15 mg Tablet
- 400 mg Injection
Max: 30 mg
Initial: 10 mg/day
Usual Dose Range: 10-30 mg
Brexpiprazole: Formulations available, usual dose range for schizophrenia and max dosing?
Formulations: 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg Tablet (Rexulti)
Max: 4 mg
Initial: 1 mg/day for 4 days
Usual Dose Range: 2-4 mg
CrCL < 60 mL/min: 2 mg/day
Amisulpride: Formulations available, usual dose range for schizophrenia and max dosing?
Formulation: 200 mg Tablet
Max: 1200 mg
Negative Sx: 50-300 mg/day
Usual Dose Range: 50-800 mg
Clozapine: Formulations available, usual dose range for schizophrenia and max dosing?
Formulation: 25 mg, 100 mg Tablets
12.5 mg ON then BD (Day 1), 25-50 mg ON (Day 2)
Usual Range: 300-450 mg
Max: 900 mg/day
What is clozapine indicated for?
Treatment resistant schizophrenia after 2 adequate trials of different antipsychotics for 6 to 8 weeks, at least one is second-generation.
Dementia-related agitation and psychosis (severe/refractory)
Suicidal schizophrenia or schizoaffective disorder
Parkinson-related psychosis
Treatment-resistant bipolar
When can you initiate clozapine therapy?
TWC > 3.5 X 10^9/L (3500)
ANC > 1.5 X 10^9/L (1500)
How frequent do you need to monitor blood count for clozapine?
Every week for the first 18 weeks.
After 18 weeks, monitor monthly
What do you do for clozapine monitoring if WBC = 3.0 to 3.5 X 10^9/L OR WBC drops by 3.0 X 10^9/L AND ANC > 1.5 X 10^9/L?
Repeat WBC count 2x/week until WBC > 3.5 X 10^9/L
What do you do for clozapine monitoring if WBC = 2.0 to 3.0 X 10^9/L OR ANC = 1.0 to 1.5 X 10^9/L?
- Stop Clozapine
- Check WBC daily and monitor for signs of infections
- Resume Clozapine only if no infection is present and once WBC is > 3.0 X 10^9/L
What do you do for clozapine monitoring if WBC < 2.0 X 10^9/L OR
ANC < 1.0 X 10^9/L?
- Stop Clozapine
- Refer to hematologist and consider isolation
- Never start Clozapine again
What other indications can antipsychotics be used for besides schizophrenia?
Antiemetic in palliative care
Motor tics and adjunctive treatment in choreas and Tourette’s syndrome
Intractable hiccups
Irritability associated with Autistic Disorder
Describe the clinical presentation of hyperprolactinemia
Changes in menstrual cycle in females (irregular or stopping of menstrual periods) and/or
Abnormal breast swelling, soreness or secretion (in both men and women)
