What is the recommended approach for prescribing a long-acting injectable medication?

Prescribing Long-Acting Injectable Antipsychotics

Any patient requiring long-term antipsychotic treatment should be considered a candidate for long-acting injectable (LAI) formulations, with particular priority for those with irregular medication adherence, given the well-established relationship between non-adherence and relapse risk. 1

Patient Selection Criteria

Appropriate candidates include: 1

• Patients requiring long-term antipsychotic maintenance therapy
• Those with history of non-adherence to oral medications
• Patients who have experienced relapse due to medication discontinuation
• First-episode psychosis patients (contrary to traditional practice of waiting for multiple relapses) 1
• Patients expressing preference for less frequent dosing
• Those with difficulty managing daily oral medications due to cognitive impairment, memory deficits, or organizational challenges 2

Do not delay LAI consideration until after multiple hospitalizations - this common pitfall leads to unnecessary disease progression and functional decline. 1

Timing of Initiation

Start LAI treatment as soon as acute symptoms improve - oral or short-acting intramuscular medication is preferable during acute treatment when dosing flexibility is needed, but transition to LAI should occur promptly after stabilization. 1

Medication Selection Algorithm

Base selection on the following hierarchy: 1, 3

1. Previous medication response history - prioritize agents with documented efficacy and tolerability in the patient
2. Patient preference - discuss injection frequency, site options, and formulation characteristics
3. Side effect profile considerations:
   • For metabolic concerns: haloperidol decanoate or aripiprazole LAI preferred over risperidone LAI 4
   • For extrapyramidal symptom concerns: second-generation LAIs (risperidone, paliperidone, aripiprazole, olanzapine) preferred over first-generation 4, 5
4. Practical factors: 3
   • Injection interval (monthly vs. every 2-3 months)
   • Injection site options (gluteal vs. deltoid availability)
   • Storage requirements
   • Post-injection observation needs

Specific LAI Formulations and Dosing

Risperidone Long-Acting Injectable 6, 5

• Dose: 25-50 mg every 2 weeks (gluteal or deltoid)
• Oral supplementation: Continue oral risperidone for 3 weeks after first injection
• Reconstitution required: Must use provided diluent and inject entire vial contents immediately after mixing
• Monitoring: Significant prolactin elevation and metabolic effects (weight gain, hyperglycemia risk) 4

Paliperidone Palmitate 3

• Monthly formulation: 234 mg day 1,156 mg day 8 (both deltoid), then 117 mg monthly (deltoid or gluteal)
• Three-month formulation: Available after 4 months of monthly dosing
• No oral supplementation required

Aripiprazole LAI 3, 7

• Two-injection start (TIS) - preferred: 400 mg × 2 injections with single 20 mg oral dose
• One-injection start (OIS): 400 mg with 14 days oral supplementation
• TIS provides safer pharmacokinetics with levels within therapeutic window, avoiding supratherapeutic peaks seen with OIS 7

Haloperidol Decanoate 4

• Dose: 10-20 times daily oral dose, given every 4 weeks
• Advantages: Favorable metabolic profile
• Monitoring: Extrapyramidal symptoms, particularly akathisia

Conversion from Oral to LAI

Follow this systematic approach: 8

1. Establish current antipsychotic exposure - verify patient is actually taking and tolerating oral medication
2. Understand LAI pharmacokinetics - peak levels occur weeks after injection, requiring oral overlap
3. Calculate equivalent dosing - use established conversion ratios (typically 10-20× daily oral dose for monthly depot)
4. Plan oral supplementation period - duration varies by agent (3 weeks for risperidone, 14-21 days for aripiprazole OIS, none for paliperidone) 6, 3, 8

Special Populations

Elderly Patients 2

• Start at 25% of standard adult dose
• Maintenance doses: 25-50% of adult dose
• Increased risk: Extrapyramidal symptoms, postural hypotension, anticholinergic effects, sedation
• Monitor closely: Cognitive function, gait stability, cardiovascular parameters

First-Episode Psychosis 1

• 83% of eligible first-episode patients accept LAI when properly engaged 1
• Adherence significantly better with LAI versus oral medication 1
• Do not assume patients will refuse - use shared decision-making with evidence-based education about relapse prevention

Treatment-Resistant Schizophrenia 1

• Consider LAI trial before declaring true treatment resistance - differentiate pseudo-resistance (non-adherence) from genuine resistance
• Obtain drug levels when available to confirm adequate exposure before escalating treatment

Monitoring Requirements

Baseline assessment: 9

• Movement disorder screening (Abnormal Involuntary Movement Scale)
• ECG if age >40, cardiac history, or concurrent QT-prolonging medications
• Metabolic parameters (weight, glucose, lipids)
• Prolactin level (for risperidone/paliperidone)

Ongoing monitoring: 9

• Movement disorders every 3-6 months
• Metabolic parameters every 3-6 months
• Injection site reactions
• Early assessment (1-2 weeks) for worsening symptoms or suicidality

Critical Pitfalls to Avoid

1. Waiting for multiple relapses before offering LAI - this delays optimal treatment and worsens prognosis 1
2. Inadequate oral supplementation period - leads to subtherapeutic levels and breakthrough symptoms 6, 3
3. Assuming patients prefer oral medication - many accept LAI when benefits are explained through shared decision-making 1
4. Ignoring metabolic monitoring with risperidone LAI - significant weight gain and metabolic syndrome risk requires vigilance 4
5. Improper reconstitution technique - risperidone LAI requires specific mixing procedure and immediate administration 6

Documentation and Patient Education

Prescription must specify: 6

• Exact dose and injection interval
• Injection site (gluteal vs. deltoid)
• Oral supplementation regimen and duration
• Healthcare professional administration requirement

Patient counseling points: 6

• Injection schedule and importance of adherence to appointments
• Expected timeline for therapeutic effect
• Oral supplementation requirements
• Monitoring needs (labs, movement assessments)
• Signs requiring immediate medical attention (priapism, severe extrapyramidal symptoms, metabolic decompensation)
• Pregnancy considerations and registry enrollment if applicable