Schizophrenia Flashcards
How may iatrogenic causes lead to psychotic symptoms?
Increase dopaminergic transmission (levodopa, dopamine agonists) or serotonergic neurotransmission
How may alcohol and psychoactive substance misuse lead to psychosis?
Drug withdrawal and alcohol withdrawal can predispose person to psychosis
3 examples of drugs that can lead to schizophrenia?
Alcohol, benzodiazepines, barbiturates, antidepressants, corticosteroids, CNS stimulants (Amphetamines), hallucinogens (LSD, cannabis, volatiles), beta blockers (propanolol), dopamine agonists (levodopa, bromocriptine)
Factors that prolong the course of schizophrenia?
Poor adherence with antipsychotic medications
Non pharmacological treatment for schizophrenia
Individual Cognitive behavioral therapy
Electroconvulsive therapy (ECT) - for TR schizophrenia
Repetitive Transcranial magnetic stimulation (rTMS)
Psychosocial rehabilitation programs: improving patient’s adaptive functioning
Therapeutic goals of schizophrenia
- Acute stabilisation (minimise threat to self and others, minimise acute symptoms)
- Stabilisation (minimise/prevent relapse, maintain baseline functioning)
- Stable/maintenance phase (improve functioning and quality of life)
What do antipsychotic medications do?
Tranquilise without impairing consciousness and without causing paradoxical excitement
In the short term, they are used to calm disturbed patients whatever the underlying psychopathology which may be (schizophrenia, mania, toxic delirium, agitated depression)
What do antipsychotics do in schizophrenia?
Relieve symptoms of psychosis such as thought disorder, hallucinations and delusions, and prevent relapse
When is long-term treatment indicated?
After the first episode of psychosis and to prevent the illness from becoming chronic
Why is relapse often delayed after several weeks after cessation of treatment?
Adipose tissues act as depot reservoir after chronic regular usage of antipsychotics.
The antipyschotic stored in fat cells then diffuses back into bloodstream after treatment cessation, until depletion
Will a patient relapse immediately after stopping treatment?
No, relapse is often delayed after several weeks after cessation of treatment
Methods to overcome poor treatment adherence
IM long-acting injections
Community psychiatric nurse
Patient and family (caregiver) education
Mechanism of action of antipsychotics
Dopamine receptor antagonism - antagonises all dopamine receptors in all dopaminergic tracts in the brain
Blockade of dopamine receptors in which tract is the most common mechanism of all antipsychotics in reducing positive symptoms?
Mesolimbic tract
Overactivity in this region is responsible for positive symptoms of schizophrenia
What are the dopaminergic tracts in the brain?
Mesolimbic tract
Mesocortical tract
Nigrostriatal tract
Tuberoinfundibular tract
Blockade of dopamine receptors in which tracts causes adverse effects?
Mesocortical tract - dopamine blockade or hypofunction in this region results in negative symptoms
Nigrostriatal tract - modulates body movement; antipsychotic-induced dopamine blockade in this region causes EPS
Tuberoinfundibular tract - dopamine blockade in this region of the anterior pituitary leads to hyperprolactinemia → gynecomastia
What does D2 antagonism do in terms of therapeutic effects and postulated side effects?
Improve + symptoms
EPSE, hyperprolactinemia
Do all antipsychotics have serotonin modulating effects?
No, only SGA have additional mechanism on serotonin modulation
What does 5HT2A antagonism do in terms of therapeutic effects?
Improve negative symptoms
What other receptor affinities do antipsychotics have and their postulated side effects?
H1 - sedation, weight gain
alpha1 - orthostasis, sedation
M1 - memory dysfunction, peripheral anticholinergic effects
QTc interval prolongation
What does 5HT2C antagonism do?
Weight gain
What is the algorithm for schizophrenia?
Diagnosis of schizo → use a single FGA or SGA (except clozapine) → Inadequate or no response → use another single FGA or SGA (except clozapine) not previously tried → clozapine
If adequate response and no intolerable side effects and compliant → continue treatment
How is medication selection individualised for a patient?
Based on physician’s assessment of clinical circumstances, past response/failures on antipsychotics, patient needs, efficacy and side effect profiles of the therapy
What is an adequate trial of antipsychotic? What is the adequate trial of clozapine?
Antipsychotic of at least 2-6 weeks at optimal therapeutic doses
3 months
When should you consider a long-acting injectable antipsychotic?
if inadequately compliant, or if patient prefers
Long-acting injectable antipsychotics
IM haloperidol decanoate
What should you do before any IM injection?
Check platelet count to check for thrombocytopenia
When do you consider clozapine?
In those who are treatment-resistant, ie those had failed >=2 adequate trials of different antipsychotics (at least 1 should be a SGA)
What do we need to look for in FBC when put on clozapine?
Neutrophils (to check for agranulocytosis), RBCs and Hb for anemia, Platelets (for thrombocytopenia)
How often do we need to monitor for clozapine FBC monitoring?
Baseline, then weekly for first 18 weeks, then every monthly thereafter for as long as they are on the medication
Precautions to antipsychotic use
Cardiovascular disease (QTc prolongation)
Parkinsons disease - EPSE worsened by antipsychotics (dont give strong D2 antagonists that will worsen tremors - give those with low affinity, commonly quetiapine)
Prostatic hypertrophy
Angle closure glaucoma
Severe respiratory disease
Blood dyscrasias - esp for clozapine (look out for signs of infection)
Elderly with dementia - increased risks for mortality and stroke
Adjunctive treatments for acute agitation (psychiatric emergency) if patient is cooperative
Consider oral medication
(A) oral lorazepam or
(B) oral antipsychotic: risperidone
Adjunctive treatments for acute agitation (psychiatric emergency) if patient is uncooperative
If remains agitated/aggressive:
- Consider fast-acting IM injection
(a) IM lorazepam
(b) IM olanzapine
(c) IM haloperidol
(d) IM promethazine
Adjunctive treatments for catatonia (group of symptoms that usually involve a lack of movement and communication, and also can include agitation, confusion and restlessness)
Benzodiazepines
Adjunctive treatments for depression symptoms and/or negative symptoms of chronic schizophrenia
Depression: treat with suitable antidepressant - mirtazipine
Negative sx: mild-moderate efficacy with antidepressants eg some SSRIs
Which antipsychotics have to be taken with food?
Lurasidone and ziprasidone
What are examples of FGA?
Haloperidol
What are examples of SGA?
Clozapine, olanzapine, quetiapine, risperidone
What are examples of FGA IM long acting antipsychotics?
Haloperidol decanoate
How long are IM long acting antipsychotics typically dosed?
Typically dosed once a month; paliperidone is dosed every 3 months
Why does SGA have lower incidence of movement SEs?
Not as potent D2 receptor antagonism as FGA
In terms of metabolic side effects, which are the biggest offenders in causing weight gain?
Olanzapine and clozapine
FGAs are associated with what side effects compared to SGAs?
ESPE and hyperprolactinemia
In terms of metabolic side effects, which drugs are the safest?
Aripiprazole, ziprasidone, brexipiprazole
What is dystonia defined by? What are the risks and how to manage?
Type of EPSE - Muscle spasms
Risk with high-potency antipsychotics (eg haloperidol)
Management: IM anticholinergics eg bentropine or switch to lower potency antipsychotics
What is pseudo-parkinsonism defined by? How to manage?
Tremors, rigidity
Decrease antipsychotic dose (not practical), or switch to SGA
Anticholinergics PRN eg benztropine to treat the tremors, swithc to lower potency antipsychotics
What is akathisia defined by? How to manage?
Restlessness
Decrease antipsychotic dose, or switch to SGA
Clonazepam (low dose) PRN and/or propanolol OR switch to a SGA or lower-potency antipsychotic
What is tardive dyskinesia defined by? What are the risk factors and how to manage?
Involuntary movements, irreversible during onset (usually after taking more than 6 months).
Risk: FGA > SGA (lower potency at D2 receptors), worsens with anticholinergic drugs
Management: discontinue any anticholinergics, reduce antipsychotic dose, or switch to SGA, clonazepam PRN, treat with valbenazine
How do you manage hyperprolactinaemia?
Switch to aripiprazole (partial agonist at D2, can reverse effects of hyperprolactinemia)
What are metabolic side effects of antipsychotics? What are the high and low risk agents? How to manage?
Weight gain, diabetes, hyperlipidemia
High risk: olanzapine, clozapine
Low risk: lurasidone, ziprasidone, haloperidol
Management: diet, exercise
treat diabetes (eg with metformin), hyperlipidemia
Switch to lower risk agents (eg aripiprazole, brexipiprazole, lurasidone)
What are the types of side effects experienced with antipsychotics?
EPSE (dystonia, pseudoparkinsonism, akathisia, tardive dykinesia), hyperprolactinemia, metabolic, cardiovascular, CNS, hematological
What are the cardiovascular side effects of antipsychotics? How to manage?
Orthostatic hypotension - get up slowly from sitting or lying position
QTc prolongation
VTE/PE: aripiprazole lowest risk; manage emergent DVT
Which CNS side effect of antipsychotics is a medical emergency? Risk factors and management?
Neuroleptic malignant syndrome (NMS): muscle rigidity, fever, autonomic dysfunction, altered consciousness, increased CK
Risk: High-potency antipsychotics
Management: IV dantrolene (skeletal muscle relaxant), oral dopamine agonist (to reverse efx of dopamine antagonist),
Switch to SGA (give a low potency one, not haloperidol)
Hepatological side effect of antipsychotics - description, risks, management
Decreased WBC, Agranulocytosis (decreased neutrophil count)
Risk: clozapine
Management: discontinuation if severe
Monitoring parameters for side effects of antipsychotics
BMI, Fasting blood sugar, lipid panel, blood pressure, EPSE exam
Clozapine - WBC and ANC
How often should BMI be monitored?
Every3 months
How often should fasting blood sugar be monitored?
Every 3 months after initiating SGA, then annually
How often should blood pressure be monitored?
3 months after initiating SGA then annually
How often should WBC and ANC be monitored?
Weekly for first 18 weeks, then monthly
Treatment considerations for elderly
Avoid drugs with high propensity for alpha1-adrenergic blockade (orthostatic hypotension) or anticholinergic side effect (constipation, urinary retention, delirium)
Start low go slow
Simplify regime
Avoid long half life drugs
Drug disease interaction of antipsychotics
Antipsychotics worsen Parkinson’s disease symptoms
What is the interaction between drugs with CNS depressant effects?
Additive CNS effects
eg benzodiazepine and clozapine
Additive adverse effects with ___ agents
Antimuscarinic, antihistaminic, alpha1-adrenergic blockade or dopamine blockade
Is there an interaction between levodopa and antipsychotics?
Yes, mutual antagonism with antipsychotics
What is the potential effects of administering an antihypertensive together with antipsychotics?
Increased hypotensive effects
What are common CYP1A2 inhibitors
Fluvoxamine, quinolones, macrolides
Which drug is affected by CYP1A2 inhibition?
Clozapine.
Cannot use fluvoxamine with Clozapine
What is a CYP1A2 inducer?
Cigarettes
- will decrease concentration of clozapine
Can you give carbamazepine together with clozapine?
No
Increased risk of agranulocytosis with clozapine
How to evaluate therapeutic outcomes of antipsychotics?
Monitor for effectiveness of therapy
-Mental status exam
-Psychiatric rating scales
Monitor for adverse effects
-metabolic parameters: fasting blood glucose, lipids, body weight, BP etc
-EPSE: presence and severity of any treatment-emergent EPSE (drug induced pseudoparkinsonism, akathisia, tardive dyskinesia)
When can you see a reduction in agitation, aggression, hostility?
1st week
What improvements do you see in 2-4 weeks of treatment?
Decreased paranoia, hallucinations
What are late improvements seen with antipsychotics and when do they occur?
6-12 weeks: reduced delusions
3-6 months: cognitive symptoms may improve (with SGAs)
Key clinical features of schizophrenia
Positive symptoms, negative symptoms, functional impairment
What is the MOA that improves positive symptoms?
D2 antagonism (both FGA and SGA)
What is the MOA that improves mood symptoms (and possibly also negative symptoms)?
5HT2A antagonism
Clinical differences between SGA and FGA
SGA effective for both positive and mood symptoms; FGA effective mainly for positive symptoms
FGA generally has more muscle side effects; SGA generally has more metabolic side effects (weight gain, dyslipidemia, diabetes) except aripiprazole, brexipiprazole, lurasidone.
Which SGAs tend to be more sedating and more weight gain?
the “ines” - Clozapines, olanzapines, quetiapine
When is IM rapid acting used? 2 examples?
IM haloperidol or IM olanzapine.
Used when not cooperative and cannot comply orally
What is considered treatment resistant schizophrenia? Drug of choice and monitoring?
Not responsive to at least 2 adequate trials of antipsychotics (2-6 weeks at recommended dosing), of which one is a SGA.
Clozapine is drug of choice for TRS - monitor baseline and periodic FBC with ANC due to risks for agranulocytosis
How do manage a patient who is acutely agitated or aggressive?
- De-escalate
- Consider oral antipsychotic +/- benzodiazapine
- If refuse or not possible to administer oral medications, consider fast acting IM alternatives with monitoring: eg IM haloperidol 5mg with ECG + IM lorazepam 2mg
- monitor for treatment emergent adverse effects (eg dystonia, psuedoparkinsonian side effects) - treat accordingly (eg with oral or IM benztropine 2mg)
During the stabilisation phase, what can we do if poor adherence to oral medications or if patient prefers?
IM long acting antipsychotic (LAI) eg IM haloperidol decanoate
Community psychiatric nurse referral
