Podcast
Questions and Answers
There is consistent evidence showing that Amisulpride is the most effective SGA for treating negative symptoms.
There is consistent evidence showing that Amisulpride is the most effective SGA for treating negative symptoms.
False
Clozapine is recognized for its effectiveness in treating negative symptoms in all patients.
Clozapine is recognized for its effectiveness in treating negative symptoms in all patients.
False
A meta-analysis of 38 RCTs indicated a statistically significant reduction in negative symptoms with SGAs.
A meta-analysis of 38 RCTs indicated a statistically significant reduction in negative symptoms with SGAs.
True
Non-antipsychotic interventions focusing on glutamate pathways have shown consistent success.
Non-antipsychotic interventions focusing on glutamate pathways have shown consistent success.
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Augmentation with Aripiprazole has been recommended for the treatment of negative symptoms.
Augmentation with Aripiprazole has been recommended for the treatment of negative symptoms.
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Antidepressant augmentation has been proven ineffective for managing symptoms like alogia and avolition.
Antidepressant augmentation has been proven ineffective for managing symptoms like alogia and avolition.
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Topiramate is widely accepted as an effective adjunct for improving negative symptoms.
Topiramate is widely accepted as an effective adjunct for improving negative symptoms.
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Both glycine and d-serine have shown consistent positive outcomes in RCTs targeting NMDA receptors.
Both glycine and d-serine have shown consistent positive outcomes in RCTs targeting NMDA receptors.
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ECG monitoring is mandatory for patients taking pimozide.
ECG monitoring is mandatory for patients taking pimozide.
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Blood pressure monitoring is unnecessary for clozapine.
Blood pressure monitoring is unnecessary for clozapine.
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Patients using amisulpride should not require any special monitoring parameters.
Patients using amisulpride should not require any special monitoring parameters.
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Prolactin levels should be checked only at the baseline for antipsychotic medications.
Prolactin levels should be checked only at the baseline for antipsychotic medications.
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Sertindole does not require ECG monitoring when the target dose is reached.
Sertindole does not require ECG monitoring when the target dose is reached.
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Patients receiving quetiapine should have their blood pressure monitored frequently during dose titration.
Patients receiving quetiapine should have their blood pressure monitored frequently during dose titration.
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Ziprasidone requires an ECG only in specific situations.
Ziprasidone requires an ECG only in specific situations.
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Bone mineral density tests should be considered for patients with chronically raised prolactin levels.
Bone mineral density tests should be considered for patients with chronically raised prolactin levels.
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Monitoring of blood lipids should occur at baseline, three months, and then yearly for antipsychotic medication users.
Monitoring of blood lipids should occur at baseline, three months, and then yearly for antipsychotic medication users.
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Full blood count testing is required weekly for the first 18 weeks for all patients on clozapine.
Full blood count testing is required weekly for the first 18 weeks for all patients on clozapine.
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Weight should be monitored frequently for three months and then yearly for all patients on antipsychotics.
Weight should be monitored frequently for three months and then yearly for all patients on antipsychotics.
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If plasma glucose levels are out of range, the recommended action includes obtaining a fasting sample or an HbA1c test.
If plasma glucose levels are out of range, the recommended action includes obtaining a fasting sample or an HbA1c test.
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Medications like amisulpride and sulpiride do not require monitoring for renal excretion if GFR is reduced.
Medications like amisulpride and sulpiride do not require monitoring for renal excretion if GFR is reduced.
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Neutrophils should be monitored closely for patients on clozapine due to the potential for neutropenia.
Neutrophils should be monitored closely for patients on clozapine due to the potential for neutropenia.
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No antipsychotic medications require monitoring of urea and electrolytes on a regular basis.
No antipsychotic medications require monitoring of urea and electrolytes on a regular basis.
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Lifestyle advice is unnecessary if blood lipids are found outside the normal reference range for antipsychotic users.
Lifestyle advice is unnecessary if blood lipids are found outside the normal reference range for antipsychotic users.
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Study Notes
Treatment of Negative Symptoms
- Early research showed no clear evidence for the superiority of any specific Second Generation Antipsychotic (SGA) for negative symptoms.
- A meta-analysis of 38 Randomized Controlled Trials (RCTs) demonstrated a statistically significant reduction in negative symptoms with SGAs, but the effect size did not meet the threshold for clinically meaningful improvement over time.
Effective Medications for Negative Symptoms
- Amisulpride
- Cariprazine
- Olanzapine
- Quetiapine (more effective than risperidone)
- Augmentation with Aripiprazole may also be effective.
Clozapine's Role
- Clozapine is the only medication with convincing superiority in treating treatment-resistant schizophrenia (TRS), but its efficacy for negative symptoms, especially in the short term, remains uncertain.
Pharmacological Interventions Targeting Glutamate Pathways
- Non-antipsychotic interventions targeting glutamate pathways, such as metabotropic glutamate 2/3 (mGlu2/3) receptor agonists, have not been shown to be effective for negative symptoms compared to placebo.
- Drugs affecting NMDA receptors, like glycine and d-serine, have inconsistent results in RCTs regarding their impact on negative symptoms.
Antidepressant Augmentation for Negative Symptoms
- A Cochrane review suggests that augmenting treatment with antidepressants may reduce symptoms such as affective flattening, alogia, and avolition.
- Some evidence suggests efficacy for:
- Selective Serotonin Reuptake Inhibitors (SSRIs) (e.g., fluvoxamine, citalopram)
- α2 receptor antagonists (e.g., mirtazapine, mianserin)
Topiramate as an Adjunct
- Limited evidence supports the use of topiramate as an adjunct for improving negative symptoms.
Monitoring Antipsychotic Medications
- Monitoring of patients taking antipsychotic medications is generally poor in most countries.
- Strict adherence to monitoring guidelines is crucial for safe and effective use of these drugs.
Monitoring Parameters
- Urea and electrolytes (including creatinine or estimated GFR): Baseline and yearly as part of a routine physical health check. Investigate any detected abnormalities. Amisulpride and sulpiride, being renally excreted, require dose reduction if GFR diminishes.
- Full blood count (FBC): Baseline and yearly as part of routine physical health check and to detect chronic bone marrow suppression. Stop suspect medication if neutrophils fall below 1.5 x 10^9/L and refer to specialist medical care if neutrophils drop below 0.5 x 10^9/L. Note the high frequency of benign ethnic neutropenia in certain ethnic groups. Clozapine necessitates weekly FBC for 18 weeks, followed by bi-weekly monitoring for a year, and then monthly checks (schedule varies geographically).
- Blood lipids (cholesterol; triglycerides) fasting sample, if possible: Baseline, at 3 months, and yearly. Provide lifestyle advice. Consider changing antipsychotic medication or initiating statin therapy if necessary. Clozapine and olanzapine require 3-monthly checks for the first year, followed by annual checks. Some antipsychotics (e.g., aripiprazole, lurasidone) are not directly associated with dyslipidemia, but due to its high prevalence within this patient group, all patients should be monitored.
- Weight (include waist size and BMI, if possible): Baseline, frequent checks for three months, then yearly. Offer lifestyle advice. Consider switching antipsychotic medication or implementing dietary/pharmacological interventions. Clozapine and olanzapine require frequent checks for three months, followed by 3-monthly checks for the first year, then yearly monitoring. Aripiprazole, ziprasidone, brexpiprazole, cariprazine, and lurasidone are not directly associated with weight gain, but monitoring is still recommended due to the high prevalence of obesity in this patient group.
- Plasma glucose (fasting sample, if possible): Baseline, at 4-6 months, and yearly. Offer lifestyle advice and obtain fasting or non-fasting samples and HbA1c. Refer to GP or specialist if indicated. Clozapine, olanzapine, and chlorpromazine require testing at baseline, one month, and then every 4-6 months. While certain antipsychotics are not clearly linked to impaired fasting glucose, the prevalence is high within this patient group, so all patients should be monitored.
- ECG: Baseline and when the target dose is reached. Consult with or refer to a cardiologist if abnormalities are detected. Haloperidol, pimozide, and sertindole require mandatory ECGs. Ziprasidone necessitates an ECG in specific situations. The risk of sudden cardiac death is increased with most antipsychotic medications, so ideally, all patients should undergo an ECG at least yearly.
- Blood Pressure: Baseline, frequent checks during dose titration. If severe hypotension or hypertension (clozapine) is observed, slow the rate of titration. Consider switching to another antipsychotic if postural hypotension is symptomatic. Treat hypertension according to NICE guidelines. Clozapine, chlorpromazine, and quetiapine are most likely to be associated with postural hypotension. Amisulpride, aripiprazole, brexpiprazole, cariprazine, luradisone, trifluoperazine, and sulpiride are not generally linked to postural hypotension.
- Prolactin: Baseline, then at 6 months, and yearly. Change medications if hyperprolactinaemia is confirmed and symptomatic. Consider bone mineral density tests (e.g., DEXA scan) for those with chronically elevated prolactin levels. Amisulpride, sulpiride, risperidone, and paliperidone are particularly associated with hyperprolactinaemia. Asenapine, aripiprazole, brexpiprazole, cariprazine, clozapine, luradisone, quetiapine, and olanzapine are generally not associated with hyperprolactinaemia.
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Description
This quiz covers the treatment options for negative symptoms in schizophrenia, focusing on Second Generation Antipsychotics (SGAs) and specific medications such as Amisulpride and Clozapine. It also discusses the efficacy of pharmacological interventions targeting glutamate pathways. Test your knowledge on the effectiveness and classification of these treatments.
