For an adult who discontinued a 100 mg paliperidone depot injection given every 4 weeks last Friday, what oral risperidone dose is safe to restart?

Restarting Risperidone After Paliperidone Discontinuation

Start with risperidone 2 mg once daily at bedtime, which provides a safe and evidence-based dose for most adults transitioning from long-acting paliperidone. 1

Rationale for 2 mg Starting Dose

The 100 mg monthly paliperidone depot (which is the active metabolite of risperidone) has now been discontinued for approximately one week. Given paliperidone's extended half-life from depot formulation, some medication remains in the system, making a moderate starting dose appropriate rather than beginning at the lowest possible dose. 2

• The 2 mg/day target represents the current evidence-based starting point for most adult patients, based on naturalistic studies and clinical experience showing this dose balances efficacy with tolerability better than the older 6 mg target. 3
• For first-episode or treatment-naive patients, 2 mg/day should be the maximum, as doses above 4 mg/day show no additional benefit but significantly increase extrapyramidal symptom (EPS) risk. 1
• Patients previously stable on 100 mg paliperidone monthly were likely receiving adequate dopamine blockade, suggesting they can tolerate 2 mg risperidone without starting at 0.25-0.5 mg doses reserved for antipsychotic-naive elderly patients. 1, 4

Titration Strategy If Higher Doses Are Needed

If 2 mg proves insufficient after 14-21 days of stability:

• Increase by 1 mg increments every 14-21 days to minimize EPS risk, which rises sharply with rapid titration. 1, 5
• Target a maintenance dose of 4 mg/day for most patients with chronic psychotic illness, as this represents the optimal balance of efficacy and tolerability. 3
• Never exceed 6 mg/day, as doses above this threshold increase EPS risk without providing additional therapeutic benefit. 1, 6
• Patients who tolerated slower titration (5.7 days to maximum dose) had better continuation rates than those rapidly escalated (3.9 days). 5

Critical Monitoring Parameters

• Assess for EPS at every visit, as risperidone carries the highest EPS risk among atypical antipsychotics, with symptoms possible even at 2 mg/day. 1, 6
• Monitor for orthostatic hypotension, insomnia, and agitation during the first 2-4 weeks, which are common at therapeutic doses. 1, 6
• Evaluate therapeutic response within 2 weeks, as positive findings typically emerge early if the dose provides adequate coverage. 1
• Space dose increases at minimum 14-21 day intervals to allow full assessment of tolerability and avoid EPS from rapid escalation. 1

Special Population Adjustments

For elderly patients or those with dementia:

• Start at 0.25 mg at bedtime with maximum 2-3 mg/day divided twice daily. 1
• EPS can occur at doses as low as 2 mg/day in this population. 1
• Never use anticholinergics like benztropine if EPS develop, as they worsen cognition; instead reduce the risperidone dose. 1

For patients with renal or hepatic impairment:

• Begin at 0.5 mg and titrate more cautiously, as these patients show increased sensitivity to dose changes. 6

Common Pitfalls to Avoid

• Do not start at 6 mg/day based on older package insert recommendations—this dose was derived from treatment-resistant hospitalized patients and is too high for most clinical scenarios. 3
• Do not increase doses more frequently than every 14 days, as this dramatically increases discontinuation rates and EPS risk. 1, 5
• Do not assume the patient needs the same "equivalent" dose immediately—the depot formulation provided steady-state coverage that oral dosing will re-establish over days to weeks. 2
• Do not prescribe prophylactic benztropine when starting risperidone; use it only if EPS actually develop. 1