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Final doses before complete cessation of olanzapine can be as much as 1/80th of the original therapeutic dose.
True
The olanzapine dose at period 5 is 8.4 mg with a corresponding D2 occupancy of 60%.
False
At period 10, the olanzapine dose should be reduced to 1.9 mg.
False
Liquid formulations may be required to administer the final doses of olanzapine due to their small size.
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The last recorded olanzapine dose before complete cessation is 0.24 mg.
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Stopping antipsychotics can lead to the emergence of psychotic symptoms in individuals who previously did not have a psychotic disorder.
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Patients with psychotic disorders experience a lower risk of relapse if antipsychotic medication is stopped abruptly rather than tapered.
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More than half of antipsychotic prescriptions in the UK are given for psychotic conditions.
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Tardive dyskinesia is an emotional symptom that can occur from the long-term use of antipsychotics.
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Reducing or stopping antipsychotics might improve social functioning without increasing the relapse risk in the medium term.
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NICE suggests long-term use of antipsychotics in personality disorders is effective and should be encouraged.
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Somatic withdrawal symptoms from stopping antipsychotics can include anxiety and agitation.
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Relapse risk is shown to be highest within three months following abrupt discontinuation of antipsychotic medication.
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Dopaminergic withdrawal symptoms primarily affect the serotonin neurotransmitter system.
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Adrenergic withdrawal symptoms can include hypertension and risk of myocardial infarction.
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Hypersensitivity of the dopamine system following antipsychotic treatment can increase the risk of psychotic relapse.
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Complete cessation of antipsychotic medication does not lead to any change in D2/D3 receptor availability in patients with prior treatment.
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Tapering antipsychotic dosage over more than three months can help lower the risk of relapse compared to abrupt discontinuation.
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Paranoia and auditory hallucinations are categorized under serotonin withdrawal symptoms.
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Illicit drug use does not relate to the neuroadaptive effects of antipsychotic medication after treatment cessation.
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Cholinergic withdrawal symptoms may include hallucinations and confusion.
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Tardive dyskinesia may last for years due to its link with serotonin hypersensitivity.
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Abrupt discontinuation of antipsychotics shows a clear advantage over gradual tapering in reducing withdrawal symptoms.
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Clozapine is associated with mild withdrawal symptoms due to its low anticholinergic effects.
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Patients should be encouraged to abruptly discontinue their antipsychotic medications to avoid potential withdrawal symptoms.
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Discontinuation of long-term antipsychotic medication should be considered for patients in remission after three months for first episodes.
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Initial dose reduction for antipsychotic medications can range from 10% to 25% of the most recent dose, based on individual patient experience.
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If significant withdrawal symptoms occur, it is advisable to maintain the same dose of antipsychotic medication without any adjustments.
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Monitoring patients for withdrawal symptoms should occur for at least one month after a dose reduction.
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Psychosocial support is not necessary during the withdrawal period of antipsychotic medications.
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Further reductions after an initial dose decrease should be attempted immediately if the patient tolerates the change well.
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The last recorded olanzapine dosage in period 33 is 0.1 mg.
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The reduction schedule for olanzapine may take up to 48 months depending on patient tolerance.
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A reduction of 2.5 mg every 2-3 months will eventually lead to a minimum maintenance dosage of 5 mg per day.
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In period 12, the olanzapine dose is reduced to 5.5 mg with a corresponding D2 occupancy of 55%.
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A reduction from 20 mg to 5 mg of olanzapine results in a larger reduction in D2 blockade compared to reducing from 40 mg to 5 mg.
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The relationship between the dose of antipsychotics and their therapeutic effects is purely linear.
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Olanzapine reductions can be as small as 0.07 mg every 2-3 months until the medication is entirely stopped.
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Sequential halving of doses of risperidone leads to roughly consistent percentage point reductions in D2 blockade.
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The linear reduction of D2 blockade correlates with linear dosing of antipsychotics.
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A gradual reduction in antipsychotic dosage has been shown to increase the likelihood of relapse.
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The dose-response relationship for antipsychotics can be accurately described using semi-logarithmic axes.
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The hyperbolic relationship of dose and D2 receptor occupancy suggests that larger reductions in dose will yield proportional increases in D2 blockade.
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A study that reduced overall antipsychotic dose by 42% over 6 months reported an increase in relapse rates.
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Study Notes
Final Doses Before Complete Cessation
- Extremely small doses of antipsychotics are used before cessation to prevent large decreases in D2 receptor blockade
- These doses are often 1/80th of the original therapeutic dose
- Tablet splitting or liquid formulations are required for administering these small doses
Antipsychotic Withdrawal Symptoms
- Withdrawal symptoms occur because of dopamine, serotonin, histamine, acetylcholine, and noradrenaline receptor blockade
- Symptoms can be categorized as cholinergic, dopaminergic (nigrostriatal and mesolimbic or striatal), serotoninergic, histaminergic, and adrenergic
Neurobiology of Withdrawal
- Withdrawal-associated relapse is due to dopamine system hypersensitivity caused by chronic antipsychotic use
- This hypersensitivity increases psychotic relapse risk after dose reduction.
- Neuroadaptive effects of antipsychotic medication may persist for months or years
- Tardive dyskinesia, a potential side effect of antipsychotics, is linked to dopamine hypersensitivity and can persist for years after medication cessation
- Discontinuing antipsychotics may increase short-term relapse rates but long-term relapse rates converge for patients on antipsychotics and those who have discontinued
Stopping Antipsychotics
- Long-term antipsychotic use can cause side effects such as metabolic complications, tardive dyskinesia, emotional blunting, and brain shrinkage
- Reducing or stopping antipsychotics may lead to improved social functioning and cognitive function
- Antipsychotic discontinuation trials often involve abrupt cessation, which may exaggerate the true relapse- prevention properties of antipsychotics
- Discontinuation should be considered in patients who have been in remission for at least six months (first episode) or one year (multiple episodes)
- A cautious de-prescribing approach is recommended for antipsychotic medications.
Withdrawal/Discontinuation Effects of Antipsychotics
- Stopping or reducing antipsychotics can cause autonomic, somatic, motor, and psychological symptoms
- Insomnia is a common withdrawal symptom
- Psychotic symptoms can emerge in people without a pre-existing psychotic disorder due to antipsychotic cessation
- Relapse is common in patients with psychotic disorders following antipsychotic withdrawal
Tapering Antipsychotic Medications
- All patients should be informed of the risk of withdrawal symptoms when stopping or reducing antipsychotics
- Abrupt discontinuation is the most likely method to precipitate relapse or severe withdrawal
- Tapering clozapine requires caution due to its potent anticholinergic effects and severe withdrawal symptoms
Initial Dose Reduction
- Dose reduction can be based on past experience with dose reduction
- Initial reduction can be approximately 25% of the current dose
- Patients should be monitored for withdrawal symptoms or worsening psychotic symptoms for three months after reduction
- Further reductions can be attempted at the same rate (10-25% every three months) if the patient tolerates the previous reduction
Managing Significant Withdrawal
- If significant withdrawal symptoms or worsening psychotic symptoms occur, reinstate the original dose (or a portion thereof)
- Reducing dose should be delayed until stability is achieved and reductions should be more gradual (5-10% of the current dose)
Pattern of Tapering
- Antipsychotic dose and D2 receptor occupancy have a hyperbolic relationship
- This relationship suggests that linear reductions in antipsychotics will produce increasingly large reductions in D2 blockade, which may increase the risk of relapse
- Hyperbolically reducing doses requires linear reductions in D2 blockade
- Sequential halving of doses allows for gradual reductions in D2 blockade, potentially minimizing relapse risk
Table 1.12 Reductions of olanzapine dose by 2.5 percentage points of D2 occupancy
- This table provides a detailed schedule for reducing olanzapine dosages with 2.5% decreases in D2 occupancy
Table 1.13 A summary of potential reduction schedules for olanzapine
- This table suggests potential reduction schedules for olanzapine, with varying reduction periods (2-3 months)
- The process is expected to take 12-48 months, depending on patient tolerance.
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Description
Explore the complex phenomenon of antipsychotic withdrawal, including symptoms, neurobiology, and strategies for safe cessation. Understand the role of dopamine receptors in withdrawal and how chronic use affects relapse risk. This quiz delves into the latest insights on managing withdrawal and minimizing risks.
