trifluoperazine

General Information

Trifluoperazine is a high-potency phenothiazine FGA used for psychotic disorders. The label also includes short-term treatment of generalized non-psychotic anxiety, with explicit duration and dose limits (label).

The label reports that anxiety efficacy was established in a four-week multicenter outpatient study in generalized anxiety disorder (DSM-III), and cautions that this evidence does not predict usefulness in other non-psychotic conditions where anxiety-like symptoms can occur (label).

Because it is high potency, movement-disorder risk (EPS and tardive dyskinesia) is often the most clinically important tolerability constraint; this can be especially relevant when it is used outside psychosis care for anxiety (label/clinical).

As with all antipsychotics, the class boxed warning for increased mortality in elderly patients with dementia-related psychosis applies (label).

The trifluoperazine compare view, evidence feed, and print page support shared decision-making about symptom targets vs adverse effects.

Trifluoperazine’s anxiety indication is uncommon in modern practice because many alternative anxiolytics do not carry antipsychotic-class risks. When it is used, the label’s explicit dose and duration limits are typically treated as “guardrails” (label/clinical).

Mechanism of Action

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

Dopamine D2 receptor antagonism is the primary antipsychotic mechanism.

Relative “high potency” is associated with higher EPS risk at clinical doses.

• D2 receptor antagonism (antipsychotic effect).

Metabolism and Pharmacokinetics

• Trifluoperazine is hepatically metabolized; clinical titration is usually guided by symptom response and tolerability rather than serum levels (label/clinical).

Dosing and Administration

• Anxiety (non-psychotic): label describes a usual dosage of 1–2 mg twice daily and states not to exceed 6 mg/day or use longer than 12 weeks (label).
• Psychotic disorders (oral): label describes starting 2–5 mg twice daily (starting lower in small/emaciated patients) and titrating based on response (label).
• The label notes many patients show optimum response around 15–20 mg/day, though some may require 40 mg/day or more; dose is individualized (label).
• The label notes some patients may be controlled on twice-daily dosing and some on once-daily dosing after stabilization; dosing cadence is individualized to response and tolerability (label).
• Older adults are often started at lower doses and titrated more slowly due to susceptibility to hypotension and neuromuscular reactions (label).

Monitoring & Labs

• Movement symptoms (akathisia, rigidity, tremor; tardive dyskinesia screening).
• Sedation and orthostatic symptoms (falls risk).
• Hyperprolactinemia symptoms (amenorrhea, galactorrhea, sexual dysfunction).
• Duration limits when used for non-psychotic anxiety (≤12 weeks per label).
• Reassess anxiety benefit early and document a stop plan (label/clinical).

Adverse Effects

Interactions

• Additive CNS depression with alcohol, opioids, benzodiazepines, and other sedatives (clinical).
• QT-prolonging combinations and electrolyte abnormalities can increase arrhythmia risk; ECG monitoring is commonly considered when risk factors accumulate (clinical).
• Additive anticholinergic and hypotension burden with tricyclic antidepressants, first-generation antihistamines, and other anticholinergic agents can increase delirium and falls risk (clinical).

Other Useful Information

• For anxiety symptoms, non-antipsychotic options are often preferred due to the long-term movement-disorder risks associated with dopamine-blocking agents (label/clinical).
• For schizophrenia care, LAI antipsychotics are typically considered early when adherence is uncertain; trifluoperazine has no depot formulation (APA/clinical).
• When used for non-psychotic anxiety, teams often document a stop/reassess date aligned to the label duration limit to reduce inadvertent long-term exposure (label/clinical).

References

1. Trifluoperazine hydrochloride tablets prescribing information — DailyMed (2025)
2. First Generation Versus Second Generation Antipsychotics IN Adults: Comparative Effectiveness — Agency for Healthcare Research and Quality (NCBI Bookshelf) (2012)
3. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia — American Psychiatric Association (2020)
4. AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)