What are the recommended dosing regimens for long-acting injectable antipsychotics, including risperidone (Risperdal), paliperidone (Invega) palmitate, olanzapine (Zyprexa) pamoate, and aripiprazole (Abilify) monohydrate?

Long-Acting Injectable Antipsychotic Dosing

For long-acting injectable antipsychotics, start risperidone LAI at 25 mg every 2 weeks with oral supplementation for 3 weeks, paliperidone palmitate at 234 mg on day 1 and 156 mg on day 8 (both deltoid), then 117 mg monthly, olanzapine pamoate at 210-300 mg every 2-4 weeks (requires 3-hour monitoring for PDSS), and aripiprazole monohydrate at 400 mg monthly with 14 days of oral overlap.

Risperidone Microspheres (Risperdal Consta)

Initial Dosing

• Start at 25 mg intramuscularly every 2 weeks for most patients 1
• Continue oral risperidone (or another oral antipsychotic) for the first 3 weeks after initial injection because there is no immediate drug release 1
• The main release of risperidone begins at weeks 2-3 post-injection, increases during weeks 3-4, is maintained during weeks 4-6, and declines between weeks 6-7 1

Dose Titration

• Increase doses every 8 weeks (not sooner) to allow adequate assessment 1
• Maximum dose is 50 mg every 2 weeks 1
• Steady-state levels are reached by weeks 6-8 with repeated injections 1

Special Populations

• In elderly patients, start at 25% of the usual adult dose with maintenance doses ranging from 25-50% of adult doses 2
• Patients stable on conventional depot antipsychotics can be switched directly to long-acting risperidone without prior transition to oral risperidone 3

Paliperidone Palmitate (Invega Sustenna/Trinza)

Monthly Formulation (Sustenna)

• Day 1: 234 mg deltoid injection 4
• Day 8: 156 mg deltoid injection 4
• Maintenance: 117 mg monthly (deltoid or gluteal) starting at week 5 4
• No oral supplementation required due to immediate release profile 4

Safety Profile

• Treatment-emergent adverse events leading to discontinuation were similar to placebo 4
• Somnolence/sedation occurred in 5-7% versus 3% with placebo 4
• No cases of PDSS identified in clinical trial databases for paliperidone palmitate 4

Olanzapine Pamoate (Zyprexa Relprevv)

Critical Safety Requirement

• Mandatory 3-hour post-injection observation for postinjection delirium/sedation syndrome (PDSS) 4
• PDSS occurred in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients across 8 clinical trials) 4
• This is a potentially serious adverse event unique to olanzapine pamoate 4

Dosing Considerations

• Dosing ranges from 210-300 mg every 2-4 weeks depending on oral olanzapine dose equivalence 5
• Requires enrollment in a Risk Evaluation and Mitigation Strategy (REMS) program due to PDSS risk 4

Aripiprazole Monohydrate (Abilify Maintena)

Initial Dosing

• 400 mg intramuscularly monthly is the standard dose 5
• Continue oral aripiprazole for 14 days after the first injection 5
• Less likely to cause extrapyramidal symptoms compared to other antipsychotics 5

Drug Interactions

• Reduce dose in poor metabolizers of cytochrome P450 2D6 5
• Exercise caution with CYP2D6 and 3A4 drug-drug interactions; consult pharmacy references 5

General Principles for LAI Selection and Monitoring

Treatment Resistance Assessment

• To rule out "pseudo-resistance" due to non-adherence, at least one LAI trial must be given for at least 6 weeks after achieving steady state—generally requiring at least 4 months from treatment initiation 6
• This ensures adequate therapeutic exposure before concluding lack of efficacy 6

Therapeutic Dose Requirements

• The minimum dose should be the target dose (or mid-point of target dose range) for acute treatment per manufacturer's labeling 5
• If unclear, use a total daily dose equivalent to 600 mg chlorpromazine per day as the minimum therapeutic threshold 5

Clinical Positioning

• Second-generation LAIs like risperidone and paliperidone are favored over first-generation agents due to better tolerability and fewer neurological side effects 7
• LAIs are indicated for patients with recurrent relapses related to non-adherence, history of frequent relapse on oral medication, and as first-line maintenance after first episode of schizophrenia 7

Common Pitfalls to Avoid

Inadequate Oral Supplementation

• Failure to continue oral antipsychotics during the initial weeks with risperidone LAI or aripiprazole leads to subtherapeutic levels and potential relapse 1

Premature Dose Escalation

• Increasing risperidone LAI doses before 8 weeks prevents accurate assessment of response since steady-state is not reached until weeks 6-8 1

Overlooking Injection Site Requirements

• Paliperidone palmitate's first two doses must be deltoid injections to achieve appropriate loading 4
• Olanzapine pamoate requires gluteal injection only and 3-hour observation 4

Extrapyramidal Symptom Risk

• While LAIs generally have favorable tolerability, risperidone LAI showed more injection-site adverse events and extrapyramidal symptoms compared to oral antipsychotics in head-to-head trials 8
• Monitor for dose-related extrapyramidal symptoms, particularly with risperidone doses >6 mg/24 h equivalent 5