What are the monitoring guidelines for a patient on second-generation antipsychotics (SGAs), such as olanzapine (olanzapine), quetiapine (quetiapine), and risperidone (risperidone), with a history of cardiovascular disease or risk factors, and elderly patients with dementia-related psychosis?

Monitoring Guidelines for Second-Generation Antipsychotics

Before starting any second-generation antipsychotic, obtain a comprehensive baseline assessment including BMI, waist circumference, blood pressure, HbA1c, glucose, lipids, prolactin, liver function tests, urea and electrolytes, full blood count, and electrocardiogram. 1

Baseline Assessment (Before Initiation)

The following parameters must be obtained before starting treatment 1:

• BMI and waist circumference
• Blood pressure
• HbA1c and fasting glucose (if fasting sample unavailable, obtain random glucose initially, then prioritize fasting if abnormal)
• Lipid panel (fasting triglycerides and cholesterol)
• Prolactin level
• Liver function tests
• Urea and electrolytes (renal function)
• Full blood count
• Electrocardiogram 1
• Family and personal history of cardiovascular disease and diabetes 1

Early Monitoring Phase (First 6 Weeks)

Fasting glucose must be rechecked at 4 weeks following initiation. 1 This is critical for detecting early metabolic derangement, particularly with olanzapine and clozapine which have the poorest cardiometabolic profiles. 1

BMI, waist circumference, and blood pressure should be checked weekly for 6 weeks. 1 This intensive early monitoring captures the period of highest risk for weight gain and metabolic disturbance.

Intermediate Monitoring (3 Months)

All baseline measures should be repeated and reviewed after 3 months of antipsychotic treatment. 1 This includes:

• BMI and waist circumference
• Blood pressure
• HbA1c and glucose
• Lipid panel
• Prolactin
• Liver function tests
• Renal function
• Full blood count
• ECG review 1

Long-Term Monitoring (Annual)

After the 3-month assessment, repeat all measures annually. 1 For patients on metformin augmentation (recommended when starting olanzapine or clozapine), annual monitoring should also include vitamin B12 levels. 1

Special Considerations for High-Risk Populations

Elderly Patients with Dementia-Related Psychosis

Second-generation antipsychotics are NOT approved for dementia-related psychosis and carry a black box warning for increased mortality risk in this population. 2 If used off-label despite this warning:

• Olanzapine increases mortality risk (OR 2.21) and cerebrovascular events (OR 4.47) compared to placebo 3
• Risperidone increases mortality risk (OR 1.63) and cerebrovascular events (OR 3.68) compared to placebo 3
• Quetiapine increases mortality risk (OR 1.68) but shows no improvement in psychosis symptoms 3
• The incidence of death in olanzapine-treated elderly patients with dementia was 3.5% versus 1.5% for placebo 2
• Cerebrovascular adverse events (stroke, TIA) occur at significantly higher rates with olanzapine versus placebo in this population 2

Patients with Cardiovascular Disease or Risk Factors

Patients with pre-existing cardiovascular disease have substantially higher risks with antipsychotic use compared to those without cardiovascular disease. 4 The European Society of Cardiology guidelines note that antipsychotics with high potency for potassium channel blockade carry the highest risk of ventricular arrhythmias and sudden cardiac death. 1

Cardiac risk assessment is mandatory before initiation, and cardiology consultation should be obtained if positive findings are identified. 1 After starting treatment, perform a cardiac check-up, and if QTc prolongation exceeds 500 ms or new cardiac symptoms develop, treatment must be re-evaluated. 1

Avoid concomitant use of other QT-prolonging medications including Class 1A antiarrhythmics, Class III antiarrhythmics, and certain antibiotics. 5

Medication-Specific Monitoring Considerations

Olanzapine and Clozapine (Highest Metabolic Risk)

Consider adjunctive metformin when starting olanzapine or clozapine. 1 Before starting metformin, assess renal function and avoid in renal failure. 1 Start at 500 mg once daily, increase by 500 mg every 2 weeks up to 1 g twice daily based on tolerability, preferably using modified-release formulation. 1

These agents have the highest central anticholinergic activity and should be avoided when cognitive function is a priority. 1, 6

Quetiapine

Monitor for orthostatic hypotension and sedation, particularly during initial dose titration. 5 Dose reduction is mandatory in elderly patients and those with hepatic impairment, starting at 25 mg. 5

Clozapine

Follow specific clozapine monitoring guidelines for hematologic parameters before and during initiation. 1 This is in addition to the standard metabolic monitoring outlined above.

Switching Between Antipsychotics

When switching antipsychotics, use the same monitoring schedule as for initial treatment initiation (weekly BMI, waist circumference, and blood pressure for 6 weeks, then full reassessment at 3 months). 1

Critical Safety Monitoring

Monitor for neuroleptic malignant syndrome (NMS): hyperpyrexia, muscle rigidity, altered mental status, autonomic instability, elevated creatinine phosphokinase, myoglobinuria, and acute renal failure. 2 If NMS occurs, immediately discontinue the antipsychotic and provide intensive supportive care.

Monitor for drug reaction with eosinophilia and systemic symptoms (DRESS) with olanzapine exposure. 2

Responsibility for Monitoring

The psychiatrist or prescriber is responsible for ensuring that screening and monitoring is conducted. 1 However, shared care models with primary care providers are explicitly promoted in guidelines to improve adherence to monitoring protocols. 1