risperidone microspheres

General Information

Risperidone microspheres (Risperdal Consta) is a long-acting injectable formulation of risperidone dosed every 2 weeks.

It is used for schizophrenia maintenance and bipolar I maintenance (monotherapy or adjunct, per labeling), often when relapse risk is driven by inconsistent daily dosing.

A defining operational feature is the initial release lag: label initiation includes an oral overlap period (often ~3 weeks) to maintain coverage while sustained depot release begins.

Pharmacology mirrors risperidone/paliperidone-class D2/5-HT2A blockade: prolactin elevation and EPS are frequent clinical constraints, and metabolic monitoring remains important.

Risperidone microspheres is most often selected when teams want a long-established depot option and can support the operational complexity of overlap initiation and q2wk visits. The trade-offs are a higher prolactin signal and meaningful EPS risk in some patients, plus the need for an oral overlap during initiation and some missed-dose scenarios.

Mechanism of Action

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

Risperidone is a dopamine D2 and serotonin 5-HT2A antagonist with additional alpha-adrenergic and histaminergic activity.

Therapeutic effect is generally attributed to sustained D2 receptor occupancy with serotonergic modulation, while prolactin elevation and EPS reflect dopamine blockade in pituitary and nigrostriatal pathways.

• Dopamine D2 receptor antagonism.
• Serotonin 5-HT2A receptor antagonism.
• Alpha-adrenergic blockade contributing to orthostasis in some patients.
• Histamine H1 activity contributing to sedation and weight change.

Metabolism and Pharmacokinetics

• Risperidone is metabolized primarily via CYP2D6 to the active metabolite 9-hydroxyrisperidone (paliperidone); genetic metabolizer status and 2D6 inhibition can influence exposure.
• The microsphere depot has a delayed onset of sustained release; initiation requires oral overlap, and missed-dose protocols may also require supplementation.
• Although the active moiety half-life is measured in days, depot release and elimination extend for weeks after the last injection; clinical effects can persist for 7–8 weeks.

Dosing and Administration

• Administration is intramuscular every 2 weeks. Dose selection is individualized to response and tolerability within labeled ranges.
• Initiation includes an oral overlap period (often ~3 weeks) because the microsphere formulation has a delayed onset of sustained release.
• Missed-dose management is time-dependent and may require oral supplementation; many clinics use standing protocols that specify when to administer the injection and when to re-start overlap.
• Switching from oral risperidone or another antipsychotic is individualized to relapse risk, prior response, and tolerability, with careful attention to overlap logistics.

Monitoring & Labs

• Weight/BMI and waist circumference; fasting lipids and glucose/HbA1c at baseline and periodically.
• Movement disorder monitoring (parkinsonism, akathisia, tardive dyskinesia).
• Prolactin-related symptoms; targeted labs when indicated.
• Blood pressure/orthostasis monitoring in older adults or antihypertensive co-use.
• ECG monitoring when baseline QTc risk is elevated or QT-prolonging co-medications are present.

Adverse Effects

Interactions

• Strong CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) can raise risperidone exposure; monitor for EPS and prolactin-related adverse effects and adjust per clinical response.
• Enzyme inducers (e.g., carbamazepine) can lower exposure and increase relapse risk; depot dose adjustment is less flexible than daily oral dosing.
• Additive CNS depression and orthostasis can occur with alcohol, benzodiazepines, opioids, or antihypertensives; individualize monitoring based on baseline risk.
• Combined dopamine antagonists increase EPS burden; movement-disorder monitoring is commonly used when combinations are unavoidable.

Other Useful Information

• The initiation overlap window is the common operational failure mode; checklists that specify overlap duration and follow-up timing reduce early relapse risk.
• Because clinical effects persist for weeks after discontinuation, side effect planning often emphasizes early detection rather than waiting for rapid washout.
• When bipolar maintenance is the target, align depot follow-up with mood stabilizer monitoring and care plans (see bipolar hub).

References

1. Risperdal Consta (risperidone) Long Acting Injection — Prescribing Information — DailyMed (2025)
2. Long Acting Injectable Risperidone: Efficacy AND Safety OF THE First Long Acting Atypical Antipsychotic — American Journal of Psychiatry (2003)
3. The CANMAT and ISBD Guidelines for the Management of Patients With Bipolar Disorder: 2021 Update — Bipolar Disorders (2021)Guidelinebipolarclinical
4. AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)