risperidone (Perseris)

General Information

Perseris is a monthly subcutaneous long-acting risperidone formulation used for schizophrenia maintenance.

Pharmacology mirrors risperidone/paliperidone-class D2/5-HT2A blockade: prolactin elevation and EPS can be limiting, and metabolic monitoring remains important.

Perseris has a distinct absorption profile with two peaks after each injection (early hours and again around 10–14 days). Label describes an apparent terminal half-life of risperidone of ~9–11 days, driven largely by depot release rather than hepatic clearance.

For depot comparisons and planning across antipsychotics, see the LAI Navigator and the compare tool.

Perseris is often chosen when a monthly visit is feasible and clinicians prefer a subcutaneous option that does not typically require the multi- week oral overlap needed for risperidone microspheres (Consta). Practical constraints include injection-site reactions, prolactin/EPS monitoring, and the need for clinic training on the kit preparation.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Risperidone antagonizes dopamine D2 and serotonin 5-HT2A receptors with additional activity at α1-adrenergic and histamine H1 receptors.

D2 blockade supports antipsychotic effects but contributes to prolactin elevation and EPS risk, especially at higher doses.

• Antagonist at dopamine D2 and serotonin 5-HT2A receptors.
• Antagonist at α1-adrenergic and histamine H1 receptors (orthostasis/sedation).
• Minimal muscarinic receptor affinity.

Metabolism and Pharmacokinetics

• Risperidone is metabolized primarily via CYP2D6; interaction profiles matter when adding strong 2D6 inhibitors.
• Perseris shows two absorption peaks after injection (early and again around 10–14 days). Label describes an apparent terminal half-life of risperidone of ~9–11 days related to slow depot release and absorption.

Dosing and Administration

• Establish oral tolerability before initiating depot therapy when feasible. Perseris is administered as a monthly subcutaneous injection.
• Dose selection is label-based (commonly 90 mg or 120 mg monthly depending on prior oral dose). Verify conversion tables and administration details in the product label.
• Perseris does not typically require the multi-week oral overlap used for risperidone microspheres (Consta), but missed-dose handling should be documented at initiation.
• Because depot effects persist between visits, dose adjustments and response assessment often span multiple injection cycles.

Monitoring & Labs

• Weight/BMI and waist circumference; fasting lipids and glucose/HbA1c at baseline and periodically.
• Movement disorder monitoring (akathisia, parkinsonism, tardive dyskinesia), especially after initiation and dose adjustments.
• Prolactin-related symptom review (sexual dysfunction, menstrual changes, galactorrhea).
• Injection site assessment and documentation (site rotation, local reactions).

Adverse Effects

Interactions

• Strong CYP2D6 inhibitors (some SSRIs) can increase risperidone exposure and adverse effects; consider dose adjustment and closer monitoring.
• Enzyme inducers can lower exposure and increase relapse risk; depot dose adjustments are less "steerable" than with daily oral dosing.
• Additive CNS depression and orthostasis can occur with alcohol, benzodiazepines, opioids, and antihypertensives; monitor falls risk.

Other Useful Information

• Depot outcomes are strongly influenced by clinic workflow: reminders, reliable scheduling, and clear documentation of last injection date and site.
• For patients and caregivers, it can help to track a few practical signals between visits (sleep, appetite/weight, restlessness, and sexual side effects). Because dose changes take time to show up, a simple symptom log can make the next follow-up more actionable.
• Use the schizophrenia hub for relapse-prevention pathways and education links.

References

1. Perseris (risperidone) Extended Release Injectable Suspension — Prescribing Information — DailyMed (2025)
2. RISPERDAL (risperidone) prescribing information — DailyMed (2025)
3. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia — American Psychiatric Association (2020)
4. Comparative Efficacy AND Tolerability OF 15 Antipsychotic Drugs IN Schizophrenia: A Multiple Treatments Meta Analysis — The Lancet (2013)Meta-analysisschizophreniaefficacy
5. AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)