fluphenazine decanoate

General Information

Fluphenazine decanoate is a long-acting injectable formulation used for schizophrenia maintenance when depot dosing supports adherence.

It is a high-potency first-generation antipsychotic (FGA) with strong dopamine D2 antagonism. Compared with many SGAs it tends to have lower metabolic burden but higher risk of EPS and tardive dyskinesia.

Depot dosing is typically every 2–4 weeks. Because drug release is prolonged, clinical changes after dose adjustments can lag, so response assessment often spans multiple injection cycles.

For depot interval comparisons and practical workflow, see the LAI Navigator and the compare tool.

Fluphenazine decanoate is generally used when an FGA is effective and the team prefers a depot schedule to reduce missed-dose relapse. Major constraints are movement-disorder risk (including tardive dyskinesia), QTc considerations, and slower dose "steerability" versus oral therapy.

Mechanism of Action

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

Fluphenazine is a potent dopamine D2 receptor antagonist with antipsychotic effects mediated primarily through dopamine blockade.

High D2 occupancy contributes to clinical efficacy but also to higher EPS and prolactin-related adverse effects relative to many SGAs.

• Potent dopamine D2 receptor antagonist.
• Minimal anticholinergic receptor affinity relative to low-potency FGAs.
• Variable histamine and adrenergic receptor activity; orthostasis is usually modest.

Metabolism and Pharmacokinetics

• Fluphenazine is metabolized in part via CYP2D6; interaction burden is clinically relevant with strong 2D6 inhibitors.
• Depot dosing provides sustained release over weeks; clinical effects and adverse effects can persist between injections and after discontinuation.

Dosing and Administration

• Confirm oral tolerability and response before depot conversion when feasible. Conversion is individualized and should follow labeling and local protocols.
• Typical depot intervals are every 2–4 weeks. Missed-dose management is time-sensitive and should be documented at initiation.
• Dose adjustments are slower than with oral therapy because depot release persists for weeks; teams often reassess across multiple cycles before concluding a regimen is ineffective.
• Because fluphenazine is a high-potency FGA, some teams proactively plan how they will recognize and manage acute dystonia, akathisia, or other severe EPS between injections (for example, by documenting a PRN plan and clear escalation steps at initiation).

Monitoring & Labs

• Movement disorder monitoring (akathisia, parkinsonism, tardive dyskinesia) including periodic AIMS-style exams.
• ECG/QTc monitoring when clinically indicated (cardiac disease, electrolyte disturbances, QT-prolonging co-medications).
• Prolactin-related symptom review (sexual dysfunction, menstrual changes, galactorrhea).
• Injection site assessment and documentation (site rotation, local reactions).

Adverse Effects

Interactions

• Strong CYP2D6 inhibitors may increase exposure and adverse effects.
• Additive QTc prolongation risk occurs with other QT-prolonging agents; individualize ECG monitoring to baseline risk.
• Additive CNS depression with alcohol, benzodiazepines, opioids, and sedative hypnotics; monitor falls risk and daytime functioning.
• Combining dopamine-blocking agents increases EPS burden; consider movement-disorder monitoring when combinations are unavoidable.

Other Useful Information

• Depot outcomes are strongly influenced by clinic workflow: reminders, reliable scheduling, and clear documentation of last injection date and site.
• Slow washout means adverse effects can persist for weeks after dose changes; prioritize early recognition and timely management.
• Use the schizophrenia hub for relapse-prevention pathways and education links.

References

1. Fluphenazine decanoate prescribing information — DailyMed (2024)
2. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia — American Psychiatric Association (2020)
3. Comparative Efficacy AND Tolerability OF 15 Antipsychotic Drugs IN Schizophrenia: A Multiple Treatments Meta Analysis — The Lancet (2013)Meta-analysisschizophreniaefficacy
4. AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)
5. Triple advantages of injectable long acting second generation antipsychotics: relapse prevention, neuroprotection, and lower mortality — Schizophrenia Research (2018)