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Questions and Answers
Increasing the dose of olanzapine to 30mg/day results in a 10% increase in overall response rate.
Increasing the dose of olanzapine to 30mg/day results in a 10% increase in overall response rate.
False
The research indicates that higher doses of antipsychotics do not significantly improve treatment outcomes for most patients.
The research indicates that higher doses of antipsychotics do not significantly improve treatment outcomes for most patients.
True
Clozapine has been shown to have less efficacy compared to olanzapine in treating treatment-resistant schizophrenia.
Clozapine has been shown to have less efficacy compared to olanzapine in treating treatment-resistant schizophrenia.
False
Adverse effects of antipsychotic medications are generally unrelated to the dosage prescribed.
Adverse effects of antipsychotic medications are generally unrelated to the dosage prescribed.
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The effective use of high-dose antipsychotics is recommended as a first-line treatment strategy.
The effective use of high-dose antipsychotics is recommended as a first-line treatment strategy.
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At least three different antipsychotic medications must be tried sequentially before using high doses.
At least three different antipsychotic medications must be tried sequentially before using high doses.
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The decision to prescribe high doses of antipsychotic medications should involve the multidisciplinary team.
The decision to prescribe high doses of antipsychotic medications should involve the multidisciplinary team.
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If a patient has experienced agranulocytosis, clozapine should still be considered as the first-line medication.
If a patient has experienced agranulocytosis, clozapine should still be considered as the first-line medication.
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Regular ECGs are only required at the beginning of treatment with high doses of antipsychotics.
Regular ECGs are only required at the beginning of treatment with high doses of antipsychotics.
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Patient's informed consent is optional when deciding to use high doses of antipsychotic medication.
Patient's informed consent is optional when deciding to use high doses of antipsychotic medication.
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Psychological approaches are not considered when deciding to prescribe high doses of antipsychotic medications.
Psychological approaches are not considered when deciding to prescribe high doses of antipsychotic medications.
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Adequate time for response after each dosage increment is not necessary in the process of prescribing high doses.
Adequate time for response after each dosage increment is not necessary in the process of prescribing high doses.
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Blood tests can help ensure medication adherence before prescribing high doses of antipsychotics.
Blood tests can help ensure medication adherence before prescribing high doses of antipsychotics.
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High doses of antipsychotic medication are definitively more effective than standard doses for treating schizophrenia.
High doses of antipsychotic medication are definitively more effective than standard doses for treating schizophrenia.
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Approximately 10% of hospitalized patients on antipsychotic medication are on a high dose in the UK.
Approximately 10% of hospitalized patients on antipsychotic medication are on a high dose in the UK.
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The optimal efficacy of antipsychotic medication is typically observed at low doses.
The optimal efficacy of antipsychotic medication is typically observed at low doses.
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LAI risperidone at 100 mg 2-weekly provides greater benefits than 50 mg 2-weekly.
LAI risperidone at 100 mg 2-weekly provides greater benefits than 50 mg 2-weekly.
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Increasing dosages of antipsychotic medications consistently lead to significant increases in dopamine occupancy beyond a certain threshold.
Increasing dosages of antipsychotic medications consistently lead to significant increases in dopamine occupancy beyond a certain threshold.
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Studies indicate a clear benefit from escalating the dosage of antipsychotic medications for patients unresponsive to standard treatment.
Studies indicate a clear benefit from escalating the dosage of antipsychotic medications for patients unresponsive to standard treatment.
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The primary mechanism of action for antipsychotic medications involves agonism at post-synaptic dopamine receptors.
The primary mechanism of action for antipsychotic medications involves agonism at post-synaptic dopamine receptors.
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Some studies show treatment efficacy in patients with treatment-resistant schizophrenia, although the results vary widely.
Some studies show treatment efficacy in patients with treatment-resistant schizophrenia, although the results vary widely.
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Study Notes
High-Dose Antipsychotic Medication: Prescribing and Monitoring
- No firm evidence suggests that high doses of antipsychotic medication are more effective than standard doses for schizophrenia.
- This applies to various uses, including rapid tranquillisation, relapse prevention, persistent aggression, and acute psychotic episodes.
- 25% to 33% of hospitalized patients on antipsychotic medication are on high doses.
- A national audit of schizophrenia in 2013 found that 10% of community-based patients were prescribed a high dose of antipsychotic medication.
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Dose-response effects of antipsychotic medications do not show greater efficacy for doses above licensed ranges.
- Efficacy is optimal at relatively low doses:
- 4 mg/day risperidone
- 300 mg/day quetiapine
- 10 mg olanzapine
- LAI risperidone at 100 mg 2-weekly is not more effective than 50 mg 2-weekly.
- 320 mg/day ziprasidone is not better than 160 mg/day.
- Efficacy is optimal at relatively low doses:
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Mechanisms of action: Antipsychotics primarily exert their effect through dopamine receptor antagonism or partial agonism.
- Refractory symptoms may not arise from dopamine pathway dysfunction, leading to uncertain efficacy with increased dopamine blockade.
- Law of mass action: Increased doses lead to smaller increases in dopamine occupancy after reaching a threshold for efficacy.
- Research findings:
- Dold et al. meta-analysis of RCTs comparing standard and dose escalations in unresponsive patients showed no evidence of benefit associated with increased dosage.
- A few studies show efficacy in treatment-resistant schizophrenia (TRS), but results are mixed with design issues and poor patient standards.
- Studies demonstrated dosages equivalent to more than 10 mg chlorpromazine.
High-Dose Antipsychotics: Prescribing and Monitoring
- High-dose use should be an exceptional practice, only after standard treatments fail.
- If prescribing high doses:
- Document target symptoms, therapeutic response, and side effects.
- Use validated rating scales for ongoing risk-benefit assessment.
- Ensure close physical monitoring, including ECG.
Context and Key Findings
- Focuses on patients with first-episode schizophrenia and the effects of increasing antipsychotic doses.
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Olanzapine:
- Increased dose up to 30mg/day.
- Higher doses yield only a 4% increase in overall response rate.
- Switching to clozapine was significantly more successful.
-
Risperidone:
- Doses up to 10mg/day in non-responders presented limited benefit.
- Smaller studies on high-dose quetiapine (up to 1400mg/day) showed modest benefits.
- Larger studies of quetiapine indicated limited benefit at higher doses.
- Systematic review comparing olanzapine with clozapine for treatment-resistant schizophrenia suggested:
- Olanzapine at higher dosage may be an alternative to clozapine.
- Clozapine showed the most robust efficacy.
Adverse Effects of High-Dose Antipsychotics
- Majority of side effects are dose-related, including:
- EPS (Extrapyramidal symptoms)
- Sedation
- Postural hypotension
- Anticholinergic effects
- QTc prolongation
- Increased coronary heart disease mortality
- Evidence suggests that high-dose antipsychotic therapy is associated with a greater side-effect burden.
- Antipsychotic dose reduction from very high doses (mean 2253mg chlorpromazine equivalents per day) leads to improvements in cognition and negative symptoms.
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Description
Explore the prescribing and monitoring practices of high-dose antipsychotic medications for schizophrenia. This quiz covers the effectiveness of different dosing regimens and national audit findings on medication administration. Understand the implications for patient care and treatment efficacy.
