Antipsychotics - Schizophrenia Flashcards by Faith Wong

Clinical presentation of schizophrenia

A mix of positive symptoms, negative symptoms and functional impairment
Two or more of the following for at least 6 months (each symptom taking up a significant portion of at least a month)
» Delusions
» Hallucinations
» Disorganized speech
» Grossly disorganized or catatonic behavior
» Negative symptoms
Socio-occupational dysfunction

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Symptoms of schizophrenia are caused by medicines and substance abuse. T/F?

False.

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Non-pharmacological treatments for schizophrenia and what are they used to treat

Individual Cognitive Behavioral Therapy (CBT)
» Used in conjunction with all medications and family intervention.
» Applicable for those with schizophrenia
Electroconvulsive therapy (ECT)
» Used for treatment-resistant schizophrenia
Repetitive Transcranial Magnetic Stimulation (rTMS)
» Effective for reducing auditory hallucinations amongst patients with schizophrenia
Psychosocial rehabilitation programs: improving patient’s adaptive functioning

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Individual, group, cognitive behavioural non-pharmacological therapies

Individual - Counselling, social skills therapies, vocational rehab

Group - Interactive/social

Cognitive behavioural - CBT, Compliance therapy

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What are the different phases of treatment and their goals?

Acute Stabilization
» Goal: ↓ agitation, aggression, hostility; improve sleep
» Minimize threat to self and others
» Minimize acute symptoms
Stabilization
» Minimise/prevent relapse
» Promote medication adherence
» Optimize dose vs. adverse effects
Stable/maintenance phase
» Improve functioning and QoL

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Antipsychotic medications treatment principles

In the short term, they are used to calm disturbed patients whatever the underlying psychopathology might be.
» E.g. schizophrenia, mania, toxic delirium, agitated depression
Common indication: schizophrenia and other psychoses.
Relieve symptoms of psychosis such as thought disorder, hallucinations and delusions, and prevent relapse.
Long-term treatment is often necessary after first episode of psychosis, to prevent illness from becoming chronic.
Relapse often delayed for several weeks after cessation of treatment

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Methods to overcome poor treatment adherence

IM long-acting injections
Community psychiatric nurse
Patient and Family (caregiver) education

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MOA for antipsychotics (different nervous tracts)

Mesolimbic tract
- Blockade of dopamine receptors in the tract is the most common mechanism of action for all antipsychotic.
- Overactivity in this region is responsible for the positive symptoms of schizophrenia.
Blockade of the remaining 3 dopamine tracts will cause adverse effects:
- Mesocortical tract: dopamine blockade results in negative symptoms.
- Nigrostriatal tract: dopamine blockade results in EPSE.
- Tuberoinfundibular tract: dopamine blockade results in hyperprolactinemia

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Receptor affinities: Clinical implications

Therapeutic effects:
improves positive symptoms

Side effects:
EPSE, hyperprolactinemia

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Receptor affinities: Clinical implications

5-HT2A

Therapeutic effects:

Antidepressant effects, improve negative symptoms

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Receptor affinities: Clinical implications

5-HT2c

Side effect:

Weight gain

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Receptor affinities: Clinical implications

Side effects:

Sedation, weight gain

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Receptor affinities: Clinical implications

alpha-1

Side effects:

Orthostasis, sedation

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Receptor affinities: Clinical implications

Side effects:

Anticholinergic effects

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Receptor affinities: Clinical implications

Ikr

Side effects:

QTc interval prolongation

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Pharmacological treatment: algorithm for schizophrenia

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Use of FGA or SGA
If it doesn’t work, swap out with another FGA or SGA
If it still doesn’t work, administer clozapine
Consider clozapine + augmenting agent (FGA or SGA or ECT) and combination therapy (FGA + FGA, FGA+SAG), antipsychotic + ECT or other agent (e.g. mood stabiliser)

Key things to note for the regimen

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Medication selection is individualized for a patient
Patients require compliance to an adequate trial of antipsychotics (at least 2-6 weeks at optimal therapeutic doses.
Manage any intolerable side effects.
Consider long-acting IM If inadequately compliant.
Consider Clozapine in those who are treatment-resistant (i.e. those who had failed ≥ 2 adequate trails of different antipsychotics (at least 1 should be a SGA).
Routine hematological monitoring is required for those on Clozapine.

Adjunctive treatment for schizophrenia

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Acute agitation (psychiatric emergency)
- If patient cooperates, consider oral medication:
» Oral lorazepam, or oral risperidone (second-line)
» Oral antipsychotic +/- benzodiazepine

If patient does not cooperate, consider fast-acting IM injection:
» IM Lorazepam (2mg) + IM Haloperidol (5mg)

Catatonia
- Benzodiazepines, IM Lorazepam

Pharmacokinetics of antipsychotics

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Administer lurasidone and ziprasidone with food

Side effects of medications, risks and management

Dystonia
Pseudo-parkinsonism
Akathisia
Tardive dyskinesia
Hyperprolactinemia
Metabolic
Cardiovascular
CNS
Hematological

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Dystonia
Risks:
- High potency antipsychotics (haloperidol)
Management:
- IM anticholinergics (benzodiazepine, diphenhydramine)
- Or switch to lower-potency antipsychotics (e.g. Quetiapine, Sulpiride)
Pseudo-parkinsonism
Management:
- Decrease antipsychotic dose, or switch to SGA.
- Anticholinergics PRN (benzodiazepines)
Akathisia
Management:
- Decrease antipsychotic dose, or switch to SGA
- Clonazepam (low dose) PRN

4. Tardive dyskinesia 
Risks: 
- Higher risk of getting it on FGA than on SGA 
- Can worsen with anticholinergic drugs 
Management: 
- Discontinue any anticholinergics 
- Decrease antipsychotic use, or switch to SGA 
- Administer valbenazine or clonazepam

Hyperprolactinemia
Management:
- Switch to aripiprazole
Metabolic
Risks:
- High: olanzapine, clozapine
- Low: aripiprazole, lurasidone
Management:
- Maintain on current antipsychotic to prevent relapse, but treat the emergent diabetes (e.g. with metformin, hyperlipidemia)
- Switch to lower-risk agents (aripiprazole, brexiprazole, lurasidone)

7. Cardiovascular 
Risks: 
- Focus on: VTE/PE: 
- SGA>FGA>Aripiprazole 
Management: 
- Manage emergent DVT

CNS
Risks:
- Caused by: high potency antipsychotics (e.g. haloperidol)
- Focus on: Neuroepileptic malignant syndrome (NMS):
-Muscle rigidity, fever, autonomic dysfunction
Management:
- IV Dantrolene, oral dopamine
- Switch to SGA

9. Hematological 
Risks: 
- Caused by: Clozapine ↓ WBC
- Agranulocytosis 
Management:
- Discontinue antipsychotics if severe

Monitoring of the following side parameters and side effects:

A). General requirements

BMI
Fasting blood sugar
Lipid panel (mmol/L)
Blood pressure (mmHg)
EPSE exam

B). Drug-specific requirements
1. WBC and ANC (Clozapine)

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A). General requirements

BMI
- Side effect: weight gain
- Periodical monitoring: Q3 months when dose stabilized
Fasting blood sugar
- Side effect: diabetes mellitus
- Periodical monitoring: 3 months after initiating SGA, then annually
Lipid panel (mmol/L)
- Side effect: hyperlipidemia
- Periodical monitoring:
Low risk patients: q2-5 years
High risk patients: 3 months after initiating SGA, q6 months
Blood pressure (mmHg)
- Side effect: increase or decrease BP
- Periodical monitoring:
3 months then annually
EPSE exam
- Side effect: EPSE
- Periodical monitoring:
Weekly for first 2 weeks after initiation of new antipsychotic or until dose stabilized

B). Drug-specific requirements 
1. WBC and ANC (Clozapine)
- Side effect: 
Leucopenia / Agranulocytosis 
Periodical monitoring: 
- Weekly for first 18 weeks, then monthly

Treatment for special populations (elderly)

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Avoid drugs with high propensity for α1-adrenergic blockade or anticholinergic side effects
Simplify regime

Time course of treatment response

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Early improvements
» 1st week: reduced agitation
» 2-4 weeks: reduced paranoia and hallucinations
Late improvements
» 6-12 weeks: reduced delusions
» 3-6 months: cognitive symptoms may improve (with SGAs)

MOA of antipsychotics

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FGA and SGA
» D2 antagonism (on mesolimbic dopamine tract) improves positive symptoms
SGA only:
» 5HT2A antagonism may improve mood symptoms and also negative symptoms

Clinical differences between SGA and FGA

1. Efficacy: - SGA is effective for both positive and mood symptoms - FGA effective for mainly positive symptoms 2. Toxicity: - FGA generally has more “muscle side effects” (EPSE) - SGA: generally has more “metabolic sied effects” (except Aripiprazole, Brexipiprazole, Lurasidone etc.) 3. SGAs - The “-Ines” (e.g. clozapine, olanzapine, quetiapine) >> Relatively more sedating, more weight gain - The ‘-ones’ or ‘-piprazoles) >> Relatively less sedating, less weight gain

Pharmacotherapy management for the different schizophrenia phases

1. Acute Stabilization Phase - Goal: reduce agitation, aggression, hostility, improve sleep - If acutely agitated/aggressive: >> 1st: De-escalate >> 2nd: Consider oral antipsychotic +/- benzodiazepine >> 3rd: if refuse or not possible to administer oral medications >>> Consider fast-acting IM alternatives with monitoring (IM haloperidol + IM Lorazepam) - Monitor for treatment-emergent adverse effects >> E.g. dystonia, pseudo-parikinsonism side effects: treat accordingly (e.g. oral or IM benztropine 2mg) 2. Stabilization and maintenance phase - If poor adherence to oral medication, or if patient prefers IM, consider: >> IM long-acting antipsychotic, e.g. IM haloperidol decanoate

Haloperidol dose

5-15mg/day

Clozapine dose

900mg max

Olanzapine dose

900mg max

Quetiapine

800mg max

Risperidone

2-6mg/day starting dose

Haloperidol decanoate

max 300mg/4wk

Risperidone long-acting

starting dose: 25-37.5mg/2weeks | max: 50mg/2 weeks

Antipsychotics - Schizophrenia Flashcards

(33 cards)