Antipsychotics - Schizophrenia Flashcards
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
Symptoms of schizophrenia are caused by medicines and substance abuse. T/F?
False.
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
Individual, group, cognitive behavioural non-pharmacological therapies
Individual - Counselling, social skills therapies, vocational rehab
Group - Interactive/social
Cognitive behavioural - CBT, Compliance therapy
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
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
Methods to overcome poor treatment adherence
- IM long-acting injections
- Community psychiatric nurse
- Patient and Family (caregiver) education
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
Receptor affinities: Clinical implications
D2
Therapeutic effects:
improves positive symptoms
Side effects:
EPSE, hyperprolactinemia
Receptor affinities: Clinical implications
5-HT2A
Therapeutic effects:
Antidepressant effects, improve negative symptoms
Receptor affinities: Clinical implications
5-HT2c
Side effect:
Weight gain
Receptor affinities: Clinical implications
H1
Side effects:
Sedation, weight gain
Receptor affinities: Clinical implications
alpha-1
Side effects:
Orthostasis, sedation
Receptor affinities: Clinical implications
M1
Side effects:
Anticholinergic effects
Receptor affinities: Clinical implications
Ikr
Side effects:
QTc interval prolongation
Pharmacological treatment: algorithm for schizophrenia
- 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
- 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
- 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
Administer lurasidone and ziprasidone with food
Side effects of medications, risks and management
- Dystonia
- Pseudo-parkinsonism
- Akathisia
- Tardive dyskinesia
- Hyperprolactinemia
- Metabolic
- Cardiovascular
- CNS
- Hematological
- 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)
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)
- Avoid drugs with high propensity for α1-adrenergic blockade or anticholinergic side effects
- Simplify regime
Time course of treatment response
- 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
- 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
- Efficacy:
- SGA is effective for both positive and mood symptoms
- FGA effective for mainly positive symptoms - Toxicity:
- FGA generally has more “muscle side effects” (EPSE)
- SGA: generally has more “metabolic sied effects” (except Aripiprazole, Brexipiprazole, Lurasidone etc.) - 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
- 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)
- 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
