What is the recommended approach for initiating antipsychotic (antipsychotic medication) therapy?

How to Start an Antipsychotic

Before initiating antipsychotic treatment, obtain comprehensive baseline metabolic and cardiac monitoring including BMI, waist circumference, blood pressure, HbA1c, glucose, lipids, prolactin, liver function tests, urea and electrolytes, full blood count, and electrocardiogram. 1

Pre-Treatment Assessment and Monitoring

Baseline Laboratory and Physical Measurements

• Obtain the following measures before starting any antipsychotic: BMI, waist circumference, blood pressure, HbA1c, glucose, lipids, prolactin, liver function tests, urea and electrolytes, full blood count, and electrocardiogram 1
• Recheck fasting glucose 4 weeks after initiation (if fasting sample unavailable, obtain random glucose initially and follow with fasting if abnormal) 1
• Monitor BMI, waist circumference, and blood pressure weekly for 6 weeks after starting treatment 1
• Repeat all baseline measures at 3 months, then annually thereafter 1

Medical Exclusions

• Rule out physical illnesses that can cause psychosis before initiating antipsychotic treatment 1
• Assess for cardiovascular disease (history of myocardial infarction, ischemic heart disease, heart failure, conduction abnormalities), cerebrovascular disease, or conditions predisposing to hypotension 2, 3

Initial Dosing Strategy

First-Episode Psychosis

Start with low doses to minimize extrapyramidal side effects and encourage future adherence. 1

• Risperidone: Start at 2 mg/day (first-line option) 1
• Olanzapine: Start at 7.5-10 mg/day (first-line option) 1
• Quetiapine: Start at 50-150 mg/day (high second-line option) 4
• Maximum dose in first-episode psychosis should not exceed 4-6 mg haloperidol equivalent to avoid extrapyramidal side effects 1

Multi-Episode Schizophrenia

• Risperidone: 1.25-3.5 mg/day (first-line) 4
• Quetiapine: 100-300 mg/day (high second-line) 4
• Olanzapine: 7.5-15 mg/day (high second-line) 4
• Aripiprazole: 15-30 mg/day (high second-line) 4

Special Populations

Elderly Patients:

• Start quetiapine at 50 mg/day, increase in 50 mg increments based on clinical response and tolerability 2
• Use extra caution with dose escalation in elderly patients 2

Hepatic Impairment:

• Start quetiapine at 25 mg/day, increase daily in 25 mg increments to 50 mg/day to reach effective dose 2

Dose Titration Principles

Timing of Dose Adjustments

After initial titration, increase antipsychotic dose only at widely spaced intervals (14-21 days) if response is inadequate, and only within the limits of sedation and extrapyramidal side effects. 1

• Avoid large initial doses, as they increase side effects without hastening recovery 5
• Titrate based on tolerability and therapeutic response 1
• Allow 4-6 weeks to determine efficacy, with antipsychotic effects typically becoming apparent after 1-2 weeks 5

Dose Modifications with Drug Interactions

• With potent CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir): Reduce quetiapine dose to one-sixth of original dose; when inhibitor discontinued, increase dose by 6-fold 2
• With chronic CYP3A4 inducers (phenytoin, carbamazepine, rifampin): Increase quetiapine dose up to 5-fold of original dose; when inducer discontinued, reduce to original level within 7-14 days 2

Metabolic Risk Management

High-Risk Antipsychotics (Olanzapine, Clozapine)

When starting olanzapine or clozapine, consider adjunctive metformin to minimize cardiometabolic risk. 1

• Assess renal function before starting metformin (avoid in renal failure) 1
• Metformin dosing: Start 500 mg once daily, increase in 500 mg increments every 2 weeks up to 1 g twice daily based on tolerability 1
• Use modified-release preparation if available to minimize gastrointestinal side effects 1
• Monitor annually: liver function, HbA1c, renal function, and vitamin B12 1

Antipsychotics to Avoid in Specific Conditions

• Diabetes, dyslipidemia, or obesity: Avoid clozapine, olanzapine, and conventional antipsychotics (especially low- and mid-potency) 4
• Parkinson's disease: Quetiapine is first-line 4
• QTc prolongation or congestive heart failure: Avoid clozapine, ziprasidone, and conventional antipsychotics (especially low- and mid-potency) 4
• Cognitive impairment, constipation, xerophthalmia, xerostomia: Prefer risperidone, with quetiapine high second-line 4

Patient and Family Engagement

Shared Decision-Making

• Discuss potential risks and benefits with the patient (if clinically feasible) and surrogate decision maker before initiating treatment 1
• Include families in the assessment process and treatment plan, providing emotional support and practical advice 1, 5
• Educate families and social network about the nature of the problem, treatments, and expected outcomes 1

Setting and Timing

• Provide treatment in outpatient services or home if effective intervention is possible in these settings 1
• Commence treatment prior to crisis development (self-harm, violence, aggression) when possible 1
• Consider inpatient care if significant risk of self-harm or aggression, insufficient community support, or crisis too great for family to manage 1

Common Pitfalls to Avoid

Extrapyramidal Side Effects

Avoid extrapyramidal side effects to encourage future medication adherence. 1

• Typical antipsychotics are less well tolerated even at low doses compared to atypical antipsychotics 1
• Monitor for akathisia, which can be managed with dose reduction, switch to quetiapine or olanzapine, or adjunctive propranolol (10-30 mg two to three times daily) 1

Orthostatic Hypotension

• Minimize risk by limiting initial quetiapine dose to 25 mg twice daily 2
• If hypotension occurs during titration, return to previous dose in the titration schedule 2
• Use with caution in patients with cardiovascular disease, cerebrovascular disease, dehydration, hypovolemia, or on antihypertensive medications 2, 3

Blood Monitoring

• In patients with pre-existing low WBC or history of drug-induced leukopenia/neutropenia, monitor CBC frequently during first few months 2, 3
• Discontinue at first sign of WBC decline in absence of other causative factors 2, 3
• With severe neutropenia (ANC <1000/mm³), discontinue antipsychotic and follow WBC until recovery 2, 3

Reinitiation After Discontinuation

• If patient has been off antipsychotic for more than one week, follow initial dosing schedule 2
• If off for less than one week, gradual dose escalation may not be required and maintenance dose may be reinitiated 2