schizophrenia Flashcards
What is “Psychosis”
Psychosis is an acute and severe mental condition. Patient is describe to be out of touch with reality, and have a lack of insight
What is “Schizophrenia”
Schizophrenia is a form of psychosis. “Chronic psychosis”
Syndrome of disorganized and bizarre thoughts, delusion, hallucinations, inappropriate affect and impaired psychosocial functioning
What are the most common symptoms of Schizophrenia
Delusion and hallucinations (auditory, olfactory, visual, gustatory, tactile)
When is the onset of Schizophrenia?
Most commonly during early adulthood and adolescence
What are the class of diagnoses with associated psychotic symptoms
1) Organic disorders
2) Affective disorders
3) Schizophrenia
What are some of the organic disorder associated with psychotic symptoms?
1) Iatrogenic (drug) causes
2) Psychosis related to alcohol/ psychoactive substance abuse
3) Parkinson’s disease
4) Epilepsy
5) Dementia
6) Endocrine disorders
7) Cerebral lesions
8) Nervous system illness: Infections, Genetic
9) Metabolic disorders/ Physiological disturbances affecting nervous system
What are some of the affective disorders presenting with psychotic symptoms
1) Post-partum depression
2) Psychotic depression
3) Mania
What are the neurotransmitters involved in Schizophrenia
1) Dopamine
2) 5-HT
3) Glutamate
What are the predisposing factors implicated in the genesis and course of Schizophrenia?
1) Genetics
2) Neurodevelopmental effects
3) Physical, psychological, social factors in infancy and early childhood
4) Environment in utero
5) Personality
What are the precipitating factors implicated in the genesis and course of Schizophrenia?
1) Drug-induced (e.g. Benzodiazepine, Dopamine agonist, Psychoactive substances, alcohol)
2) Cerebral tumours, injury
3) Personal misfortune
4) Environment of high expressed emotion
What are the perpetuating (prolonging) factors implicated in the genesis and course of Schizophrenia?
1) Lack of support
2) Poor adherence to antipsychotic medications
3) Social withdrawal
4) Secondary demoralization
Where are the potential loci for genetic predisposition located at?
Chromosome 6, 8, 13, 15, 22
What are the DSM-5 criteria for Schizophrenia?
1) Two or more of the following symptoms, persisting for at least a 1 month period: Delusions, hallucination, disorganized speech, grossly disorganized or catatonic behaviour, negative symptoms
2) Social/ Occupational dysfunction
3) Continuous signs of disorder for at least 6 months. Inclusive of at least 1 month of symptoms mentioned in (1).
4) Schizoaffective or mood disorder has been excluded
5) NOT due to a medical disorder or substance use
6) If history of a pervasive development disorder is present, at least 1 months of hallucination and delusions
What are the positive symptoms of Schizophrenia?
1) Disorganized speech
2) Grossly disorganized or catatonic behaviour
3) Hallucinations
4) Delusions
What are the negative symptoms of Schizophrenia?
1) Affective flattening
2) Alogia (characterized by a lack of speech)
3) Anhedonia (inability to feel pleasure in normally pleasurable activities)
4) Avolition
What history must be taken prior to diagnosis and treatment?
1) History of present illness
2) Psychiatric history
3) Substance use history
4) Complete medical and medication history
5) Family, occupational, social, forensic, development history
What other evaluations must be conducted prior to diagnosis and treatment?
1) Physical and neurological exam
2) Mental state exam
3) Labs and other investigation
In mental state exam, what do you need to assess for?
Suicidal/ homicidal ideations and risks
Why do we conduct labs test for diagnosis?
To exclude general medical conditions or substance-induced symptoms
Why do we measure BMI for physical exam?
Antipsychotic medications can cause weight gain
What are the non-pharmacological treatments for Schizophrenia?
1) Individual Cognitive behavioural therapy (CBT)
2) Electroconvulsive therapy
3) Repetitive transcranial magnetic stimulation (rTMS)
4) Psychosocial rehab programs
What is electroconvulsive therapy used for?
For treatment of treatment-resistant schizophrenia
How can repetitive transcranial magnetic stimulation help?
It is effective in reducing auditory hallucinations in Schizophrenia
Individual cognitive behavioural therapy is used in conjunction with?
Medication and family intervention
What are the different phases of treatment?
1) Acute stabilization
2) Stabilization
3) Stable/ maintenance phase
What are the therapeutic goals during acute stabilization phase?
1) Minimize threat to self and others
2) Minimize acute symptoms
3) Improve role functioning
4) Identify appropriate psychological interventions
5) Collaborate with family and caregivers
What are the therapeutic goals during stabilization phase?
1) Prevent relapse
2) Promote medication adherence
3) Optimize dose
4) Manage adverse effects
What are the therapeutic goals during stable/maintenance phase?
1) Improve functioning and QOL
2) Maintain baseline functioning
3) Optimize dose and monitor for adverse effects (Tardive dyskinesia)
4) Monitor for prodromal symptoms of relapse
What are antipsychotic medications used for?
To calm disturbed patients whatever the underlying psychopathology which may be
What are the common indications for antipsychotics?
1) Schizophrenia
2) Acute mania
3) Short-term adjunctive management of severe anxiety or psychomotor agitation, violent behaviour
How are antipsychotic different from benzodiazepines?
Antipsychotics induce tranquilizing effects without impairing consciousness of patient.
What are antipsychotics used for in Schizophrenia?
To relieve symptoms of psychosis such as thought disorder, hallucination and delusions, and prevent relapse
Are antipsychotic effective in apathetic withdrawn patients/ patients with more negative symptoms?
Less effective
Which group of patient respond better to antipsychotics?
Patients with acute symptoms of Schizophrenia respond better than those with chronic symptoms
Describe the duration of treatment for Schizophrenia
It is a long-term treatment after first episode to prevent illness from becoming chronic
Onset of Schizophrenia relapse after cessation of treatment? Explain the duration
Delayed for a few weeks after cessation. This is due to adipose tissues acting as depot reservoir after chronic usage of antipsychotics
What are the methods to overcome poor treatment (Schizophrenia) outcome?
1) IM long-acting injections
2) Community psychiatric nurse
3) Patient and family/ caregiver education
What are the 4 dopaminergic tract? Which of the 4 tracts are targeted for treatment?
1) Mesolimbic tract (Main)
Blockage of the other 3 tracts causes side effects:
2) Mesocortical tract
3) Nigrostriatal tract
4) Tuberoinfundibular tract
What is mesolimbic tract responsible for?
Overactivity of this region leads to positive symptoms
What are the side effects in relation to the other dopaminergic tract
Blockage of
1) Mesocortical tract causes negative symptoms
2) Nigrostriatal tract causes extrapyramidal side effect (EPSE)
3) Tuberoinfundibular tract causes hyperprolactinemia
What are the symptoms of EPSE?
1) Akathisia (Involuntary movements/ restlessness)
2) Pseudo-parkinsonism (Resting tremors)
3) Tardive dyskinesia (Orofacial movements)
4) Dystonia
What are the other side effect in relation to off-target receptor binding?
Antagonism of:
1) H1 receptors leads to sedation/ weight gain
2) alpha-1-adrenergic receptor leads to orthostatic hypotension, sedation
3) M1 receptors leads to peripheral anticholinergic effects, memory dysfunction
4) IKr receptors leads to QTc interval prolongation (pro-arrhythmic)
What are the first-line choice for treatment of schizophrenia?
All antipsychotics (First gen/ Second gen) are first-line, except clozapine.
How many failed trials must be reached before Clozapine is used?
2 failed trials with 2 different antipyschotics, of which one is a SGA. Patient will be considered treatment resistant
When is an antipsychotic treatment considered adequate?
1) Adequate response
2) No intolerable side effect
3) Patient is compliant
What measure can be taken if patient is inadequately compliant?
Consider using a long-acting injectable antipsychotic such as
1) IM Risperidone
2) IM Paliperidone
3) IM Aripiprazole
4) IM Haloperidol
5) IM Flupenthixol
6) IM Zuclopenthixol
What MUST we monitor for clozapine? Why?
Routine haematological monitoring is required to monitor for leukocytopenia, granulocytopenia, agranulocytosis due to Clozapine use
When do we consider a patient “treatment resistant” in Schizophrenia?
When no improvement in symptoms is observed even though patient is compliant to medication at an optimal dose
How do we individualise medication selection for patient in Schizophrenia treatment?
1) Past response/ failure to antipsychotics
2) Patient’s need
3) Efficacy and side effect profile of treatment
How long is a Schizophrenia treatment trialled for?
A patient must be compliant to an adequate trial for 2-6 weeks at an optimal therapeutic dose.
How long is Clozapine trial?
3 months long to confirm therapeutic response.
If an augmenting agent (e.g. another antipsychotic) is added to Clozapine, the augmentation trial of up to 8-10 weeks is required
What are some of the comorbidities that we need to be caution of before giving antipsychotics?
DEEP MASH PCB
1) Cardiovascular disease. Contraindicated in patients with QTc prolongation. ECG required if physical exam detect cardiovascular risk
2) Parkinson’s disease. EPSE worsened by antipsychotics
3) Epilepsy, conditions that increases risk of seizure. Clozapine, chlorpromazine increases risk of seizure
4) Depression. Blockage in mesocortical tract increase negative symptoms
5) Blood dyscrasias. Especially for Clozapine
6) Elderly with dementia, increased risks (2-3x more) for stroke and mortality
7) Myasthenia gravis
8) Angle-closure glaucoma
9) Prostatic hypertrophy
10) History of jaundice
11) Severe respiratory disease
If patient is cooperative, what are some of the treatment for acute agitation
Consider oral medications.
1) Oral Lorazepam (1-2mg) OR
2) Oral Antipsychotics such as Haloperidol, Risperidone, Quetiapine, Olanzapine
3) Oral-inhaled Loxapine (10mg). Contraindicated in asthma and COPD
What are the doses for oral antipsychotics for acute agitation?
1) Haloperidol 2-5mg. Need to perform ECG
2) Risperidone 1-2mg. Most commonly use
3) Quetiapine 50-100mg
4) Olanzapine 5-10mg
If patient is NOT cooperative, what are some of the treatment for acute agitation? Include dose
Consider fast acting IM injection
1) IM Lorazepam 1-2mg
2) IM Olanzapine 5-10mg
3) IM Aripiprazole 9.75mg
4) IM Haloperidol 2.5-10 mg (With ECG)
5) IM Promethazine 25-50mg
6) Lorazepam + Haloperidol combo (with ECG)
7) Haloperidol + Promethazine combo (with ECG)
What is the issue of giving IM Lorazepam and IM Olazapine together?
Risk of cardiorespiratory fatality. Must not be given 1h of each other
What is an adjunctive treatment for Catatonia?
Benzodiazepine, PO/ IM Lorazepam
What is an adjunctive treatment for depressive symptom/ negative symptom?
Treat with a suitable antidepressant.
Special administration instruction for Lurasidone and Ziprasidone?
Administer with food
How are antipsychotics metabolize?
Hepatically. Via CYP3A4 or CYP2D6.
Except for Paliperidone ER (59% renal unchanged)
What are the first generation antipsychotics?
1) Chlorpromazine
2) Haloperidol
3) Sulpiride
4) Trifluoperazine
What is the starting dose of PO chlorpromazine?
What is the dose range/day and max dose/day?
25 mg BD or TDS
50 - 400mg/ day,
Max: 1g/day
What is the starting dose of PO Haloperidol?
What is the dose range/day and max dose/day?
0.5 -3 mg BD or TDS or 3 -5 mg BD or TDS for severe symptoms
5-15mg/day,
Max: 20mg/day
What is the starting dose of IM Haloperidol?
What is the dose range/dose and max dose/day?
IM 2-5mg/dose
IM 2-10 mg/dose,
Max: IM 18 mg
What are the second generation antipsychotics?
1) Amisulpride
2) Aripiprazole
3) Clozapine
4) Olanzapine
5) Risperidone
6) Quetiapine
7) Paliperidone
8) Ziprasidone
9) Lurasidone
10) Asenapine
11) Brexpiprazole
12) Cariprazine
13) Iloperidone
What are the main differences between SGA and FGA
SGA has significantly lesser EPSE and SGA targets serotonin receptors. SGA can be effective for both positive and negative symptoms as well.
What is common between SGA and FGA
Both antagonise D2 receptors
Which SGAs cause more weight gain, diabetes and dyslipdemia issues
Olanzapine, Clozapine
Which SGAs are good for patients with diabetes/ dyslipidemia?
Aripiprazole, Ziprasidone, Brexpiprazole
What is the starting dose of PO Clozapine?
What is the dose range/day and max dose/day?
12.5 mg ON or BD (day 1), 25-50 mg ON or BD (day 2), increase in steps of 25-50mg/day if well tolerated
200 - 450 mg/day.
Max: 900mg/day
What is the starting dose of PO Olanzapine?
What is the dose range/day and max dose/day?
10mg/day
5-20mg/day
Max: 20mg/day
What is the starting dose of IM Olanzapine?
What is the max dose/day?
2.5-10mg IM q2-4hrs
Max: 3 doses/day
What is the starting dose of PO Quetiapine?
What is the dose range/day and max dose/day?
25mg BD (day 1), 50 mg BD (day 2), 100 mg BD (day 3), 150 mg BD (day 4)
150 - 500 mg/day
Max: 800 mg
What is the starting dose of PO Risperidone?
What is the dose range/day and max dose/day?
2 mg/day in 1 or 2 divided doses.
2-6mg /day
Max: 16mg/day
Which of the antipsychotics are considered potent? Which one can reduce sucidiality?
Haloperidol and Risperidone
Clonzapine
What is the active metabolite of Risperidone?
Paliperidone
Why is “decanoate” added to antipsychotics?
Decanoate is a long aliphatic chain linked via an ester bond to the drug molecule. It is added to long-acting formulation and allowed to dissolve in an oily solvent to be injected into muscle. Slow down drug release into systemic circulation due to long molecule size
Special administration instruction for Risperidone long-acting injection?
Supplement with oral dose during 1st 3 weeks upon initiating 1st injection.
It takes time for the microspheres to break down. Hence, no effect when first injected
How is dystonia described as? How long is the onset?
Muscle spasms.
Occurs within minutes upon IM/IV injection or hours if antipsychotic taken orally
How is akathisia described as? How long is the onset?
Restlessness.
Occurs within hours to weeks
How is Tardive dyskinesia described as? How long is the onset?
Orofacial movements such as lip chewing, tongue protrusion, choreiform hand movement, pelvic thrusting
Occurs months/years to develop. 50% irreversible
How is Pseudo-Parkinsonism described as? How long is the onset?
Tremors, rigidity, bradykinesia, bradyphrenia, salivation
Occurs within days or weeks
How is dystonia managed?
Using IM anticholinergic (Benztropine/ Diphenhydramine)
How is pseudo-parkinsonism managed?
By taking anticholinergic PRN (Benztropine/ Benzhexol)
Switching to SGA or decrease antipsychotic dose
How is Akathisia managed?
Switching to SGA or decrease antipsychotic dose
Using Clonazepam/ Lorazepam/ Benzodiazepine (low dose) PRN
Using Propranolol 20mg TDS (Max 160mg/day)
Anticholinergic unhelpful
How is tardive dyskinesia managed?
Switching to SGA or decrease antipsychotic dose (Clozapine possibly effective)
Using reversible inhibitor of vesicular monoamine transporter 2 (VMAT2), Valbenazine 40-80mg/day
Using Clonazepam PRN
Discontinuing anticholinergic. Anticholinergic worsens tardive dyskinesia
What do we need to monitor for Valbenazine? Why?
We need to monitor for signs and symptoms of depression, since Valbenazine works oppositely of SSRIs
How is hyperprolactinaemia managed?
Decrease FGA dose
Use dopamine agonist (e.g. Amantadine, bromocriptine)
Switching to aripiprazole
What are the metabolic SEs of antipsychotics?
1) Weight gain
2) Diabetes
3) Hyperlipidemia
How are the metabolic SEs managed?
Switch to lower risk agents such as Lurasidone, Aripiprazole, Brexipiprazole
Treat diabetes and hyperlipidemia asap
Recommend lifestyle modifications (exercise/diet)
What are the cardiovascular SEs?
1) QTc prolongation
2) Orthostatic hypotension
3) VTE/PE
What are the CNS SEs?
1) Sedation
2) Seizure
3) Neuroleptic malignant syndrome
4) Temperature dysregulation
5) Psychogenic polydipsia
What are the s&sx of neuroleptic malignant syndrome?
1) Altered consciousness
2) Fever
3) Sweating
4) Labile BP
5) Increase Creatine Kinase
6) Muscle rigidity (stiffness)
How is neuroleptic malignant syndrome managed?
1) IV Dantrolene 50mg TDS
2) Oral dopamine agonist (Amantadine, Bromocriptine)
3) Switch to SGA
When is Clozapine discontinue?
If WBC < 3 x 10^9/L or
ANC< 1.5 X10^9/L
How do you monitor for metabolic SEs?
1) BMI
2) Fasting glucose level
3) Blood pressure
4) Lipid panel
How do you monitor for other SEs?
1) WBC/ ANC for Clozapine
2) EPSE Exam (weekly for 1st 2 weeks after initiation, then q6/q3 months for FGA, q12 months for SGA)
3) ECG (Ziprasidone)
4) Plasma prolactin
Which antipsychotic is preferred in renal impairment? Which are avoided?
Preferred: Aripiprazole
Avoided: Sulpiride, Amisulpride
Which antipsychotic is preferred in hepatic impairment?
Sulpiride, Amisulpride
Which antipsychotic is preferred in breastfeeding?
Olanzapine, Quetiapine
If patient is on Clozapine, avoid BREASTFEEDING, continue taking drug
What SEs to avoid in elderly?
Orthostatic hypotension, anticholinergic SE.
Simplify regime, start low go slow and avoid long half-life drugs
What are the drug classes that can cause DIs with antipsychotics?
1) Drugs with CNS depressant effect
2) Drugs with antimuscarinic, antihistamine, alpha-1-adrenergic blockade or dopamine blockade
3) Dopamine-augmenting agents (e.g. Levodopa)
4) Antihypertensive
5) CYP1A2 inhibitors (E.g. Macrolides, Fluvoxamine, Quinolones)
6) Carbamazepine (agranulocytosis with Clozapine)
Which SGAs are more sedating and cause more metabolic SEs?
The “-ines” (e.g. Clozapine, Olanzapine, Quetiapine) causes more weight gain, sedation
The “-ones” or “-piprazole” (e.g Aripiprazole, Risperidone) are relatively less sedating and causes less weight gain
What are the early improvements you expect to observe upon initiation of treatment?
1st week: Decrease agitation, aggression and hostility
2nd-4th weeks: Decrease paranoia, hallucinations, bizarre behaviours. Improved organization in thinking
What are the late improvements you expect to observe upon initiation of treatment?
6-12 weeks in, decrease delusions. Negative symptoms may improve
3-6 months in, cognitive symptoms may improve
