perphenazine

Antipsychotic

Brands: Etrafon, Trilafon

Last reviewed 2025-09-26

Reviewed by PsychMed Editorial Team.

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Quick answers

What is perphenazine?
Perphenazine is a mid-potency phenothiazine antipsychotic with efficacy comparable to SGAs at moderate doses and lower metabolic risk.
What is Etrafon?
Etrafon is a brand name for perphenazine (other brands: Trilafon).
What is Etrafon (perphenazine) used for?
Label indications include: Schizophrenia (adults).
What drug class is Etrafon (perphenazine)?
Antipsychotic.
What is the mechanism of action of Etrafon (perphenazine)?
Mid-potency phenothiazine antipsychotic antagonizing dopamine D2 and serotonin 5-HT2A receptors with moderate anticholinergic activity.
What strengths does Etrafon (perphenazine) come in?
Oral tablets: 2–16 mg; oral solution 4 mg/mL.
Is Etrafon (perphenazine) a controlled substance?
No — it is not scheduled as a controlled substance under U.S. federal law.

Snapshot

Class: Antipsychotic
Common US brands: Etrafon, Trilafon
Therapeutic drug monitoring not routinely recommended.
Last reviewed: 2025-09-26

Clinical Highlights

Perphenazine is a mid-potency phenothiazine antipsychotic with efficacy comparable to SGAs at moderate doses and lower metabolic risk. Used for adult schizophrenia; no depot formulation available.

CATIE trial revived interest due to comparable efficacy to several SGAs with lower metabolic burden, though EPS and tardive dyskinesia risks persist.
Compared with many SGAs, perphenazine tends to cause less weight gain and dyslipidemia, but movement-disorder risk (EPS, tardive dyskinesia) and hyperprolactinemia remain key long-term trade-offs.
Often used for clinically stable, cost-sensitive patients who can reliably take oral medication and tolerate FGAs; lack of an LAI formulation limits its role when adherence is uncertain.
Shared decision-making can support long-term use: discussions often cover restlessness, stiffness, tremor, and abnormal movements, along with how to seek help early for EPS.
The compare view helps contrast EPS, metabolic load, and cost considerations, and the Perphenazine evidence feed can support decisions about transitioning from SGAs.
Schizophrenia (adults) (FDA 1957)
Generic: All formulations available generically.

Dosing & Formulations

Oral tablets: 2–16 mg; oral solution 4 mg/mL. Initiate 4–8 mg BID/TID; titrate to 12–24 mg/day in divided doses (max 64 mg/day).

Older adults: start 2–4 mg BID and titrate slowly.
If sedation or orthostasis limits daytime functioning, shift more of the total daily dose to bedtime while maintaining symptom control.

Monitoring & Risks

Boxed warning: Increased mortality in elderly patients with dementia-related psychosis. Extrapyramidal symptoms: Parkinsonism/akathisia ~15–20% at higher doses.

Sedation: Due to H1 antagonism.
Anticholinergic effects: Dry mouth, constipation, blurred vision.
Orthostatic hypotension: From α1 blockade.
Tardive dyskinesia monitoring with AIMS is standard in long-term use.
Hyperprolactinemia can occur (amenorrhea, galactorrhea, sexual dysfunction); monitor symptoms and consider switching if clinically significant.
Baseline ECG is often obtained when cardiac risk factors or other QTc-active medications are present; electrolyte abnormalities are typically corrected before dose escalation.

Drug Interactions

CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) increase exposure—monitor EPS and adjust dose. CYP3A4 inducers (carbamazepine, rifampin) may lower levels.

Additive CNS depression with alcohol and sedatives.
Additive anticholinergic and orthostasis burden with TCAs, antihistamines, and other antipsychotics—rationalize polypharmacy when possible.
QT-prolonging combinations (methadone, macrolides, fluoroquinolones, ziprasidone) increase torsades risk; avoid when possible or monitor with ECGs.

Practice Notes

Often used for cost-sensitive patients who tolerate FGAs; EPS prophylaxis may be used when clinically indicated. Early follow-up often focuses on akathisia and rigidity screening.

Tapering is typically gradual to reduce withdrawal dyskinesias.
Regular metabolic, EPS, and cardiovascular monitoring remains standard.
For bipolar indications, coordinate with the bipolar disorder hub to integrate mood and EPS monitoring.
Document tardive dyskinesia risk discussions for long-term treatment and reassess dose reduction or alternative agents at regular intervals.

References

Perphenazine — Prescribing Information — FDA (2023)
Effectiveness of antipsychotic drugs in chronic schizophrenia (CATIE) — New England Journal of Medicine (2005)
Comparative Efficacy AND Tolerability OF 15 Antipsychotic Drugs IN Schizophrenia: A Multiple Treatments Meta Analysis — The Lancet (2013)Meta-analysisschizophreniaefficacy
The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia — American Psychiatric Association (2020)Guidelineschizophreniaclinical