For an adult patient with normal hepatic and renal function who discontinued a 100 mg paliperidone depot injection four days ago and will not restart it, what is the safest starting dose of oral risperidone?

Safest Starting Dose of Oral Risperidone After Discontinuing Paliperidone 100mg Depot

Start oral risperidone at 2 mg once daily, which represents the standard initial dose for adults with schizophrenia and provides appropriate coverage given the residual paliperidone levels still present 4 days after depot discontinuation. 1

Rationale for 2 mg Starting Dose

• The FDA-approved initial dose for schizophrenia in adults is 2 mg per day, which can be administered once or twice daily 1
• This dose balances efficacy with tolerability, as doses below 4 mg/day have been associated with insufficient clinical response when used as monotherapy 2
• Given that paliperidone 100 mg depot has a terminal half-life of approximately 23 hours for the active moiety and provides sustained release over weeks, residual drug levels will still be present at day 4, making a standard starting dose appropriate rather than a higher loading dose 3

Dose Equivalency Context

• Paliperidone is the active metabolite of risperidone, so the patient has been receiving antipsychotic coverage equivalent to oral risperidone 3
• For depot-to-oral conversion, patients on paliperidone depot 100 mg monthly would typically have been on oral doses in the mid-range (approximately 4-6 mg/day oral risperidone equivalent) 4
• Starting at 2 mg daily allows for safe transition while residual depot medication clears, with the option to titrate upward at intervals of 24 hours or greater in increments of 1-2 mg per day as tolerated 1

Titration Strategy

• After starting at 2 mg/day, assess clinical response over the first week while depot levels decline 1
• If symptoms emerge or worsen, increase to 4 mg/day (the recommended target dose for most patients) at intervals of 24 hours or greater 1, 5
• The effective dose range is 4-16 mg/day, though doses above 6 mg/day have not demonstrated superior efficacy and are associated with increased extrapyramidal symptoms 1, 2
• The optimal target dose for most patients is 4 mg/day based on naturalistic studies and clinical experience 5

Critical Monitoring Points

• Monitor closely for extrapyramidal symptoms (EPS), which can occur even at 2 mg/day, particularly in elderly patients 6
• Assess for signs of symptom breakthrough during the first 1-2 weeks as depot levels decline 3
• Watch for orthostatic hypotension, drowsiness, and insomnia during the transition period 6
• If the patient is elderly, has renal/hepatic impairment, or has demonstrated high sensitivity to antipsychotics in the past, consider starting at 0.5 mg twice daily instead 1

Special Considerations and Pitfalls

• Do not start at ultra-low doses (<2 mg/day) unless the patient has specific risk factors (elderly, renal/hepatic impairment), as these doses are associated with insufficient response and higher rates of early discontinuation 2
• Avoid rapid titration above 6 mg/day, as this increases EPS risk without additional therapeutic benefit 6, 2
• For patients with severe renal or hepatic impairment, use a lower starting dose of 0.5 mg twice daily and increase to dosages above 1.5 mg twice daily at intervals of one week or longer 1
• If the patient is elderly with dementia, the maximum dose should not exceed 2-3 mg/day, and anticholinergic agents must be avoided if EPS develop 6

Alternative Approach for High-Risk Patients

• If the patient is elderly (≥65 years), start at 0.25-0.5 mg at bedtime and titrate more slowly over 14-21 day intervals to avoid extrapyramidal effects 6, 7
• For first-episode psychosis patients, initiate at approximately 2 mg/day and do not exceed 4 mg/day 6
• Consider split dosing (e.g., 1 mg twice daily rather than 2 mg once daily) if the patient experiences peak-related side effects such as orthostatic hypotension or excessive sedation 6