thioridazine

General Information

Thioridazine is a low-potency phenothiazine FGA with prominent anticholinergic effects. It is distinguished clinically by a dose-related risk of QTc prolongation and torsades de pointes–type arrhythmias (label).

Due to its proarrhythmic risk, labeling restricts thioridazine to schizophrenia patients who have not responded to, or cannot tolerate, other antipsychotics (label).

The label highlights multiple contraindications (congenital long QT syndrome, history of arrhythmias, uncorrected hypokalemia, and combinations with other QT-prolonging drugs) and describes avoiding CYP2D6 inhibition that can raise exposure and QT risk (label).

The label recommends baseline ECG and potassium assessment and states that patients with QTc >450 msec should not receive thioridazine (label).

The thioridazine compare view, evidence feed, and print page support evaluation of lower-QT alternatives.

Thioridazine is generally treated as a last-line oral antipsychotic because of QT-related risks and extensive contraindicated drug interactions. When used, the care plan is typically ECG-anchored with a strong emphasis on interaction screening (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.

Anticholinergic activity contributes to dry mouth, constipation, and urinary retention risk.

QT prolongation is a key safety issue and is described as dose-related in labeling.

• D2 receptor antagonism (antipsychotic effect).
• Antimuscarinic activity (anticholinergic effects).

Metabolism and Pharmacokinetics

• Thioridazine metabolism involves CYP2D6; reduced CYP2D6 activity or CYP2D6 inhibition can increase exposure and QT risk (label).
• Labeling notes that a subset of patients have genetically reduced CYP2D6 activity, which can increase exposure; medication review for CYP2D6 inhibitors is treated as a safety-critical step (label/clinical).

Dosing and Administration

• The label emphasizes determining the smallest effective dose for each patient due to QT risk and restricting use to schizophrenia after failure of other agents (label).
• Adult schizophrenia dosing: label describes a usual starting dose of 50–100 mg three times daily with gradual titration as needed (label).
• The label describes total daily dose ranges of 200–800 mg/day (divided into 2–4 doses) with a maximum of 800 mg/day if necessary (label).
• Because QT risk is dose-related, clinicians commonly re-check ECG and electrolytes after dose changes and reassess therapy if QTc prolongs or if syncope/palpitations occur (label/clinical).

Monitoring & Labs

• Baseline ECG and potassium; consider periodic ECG/potassium during titration (label).
• Avoid QT-prolonging combinations; re-check medication list after any new prescription.
• Sedation, orthostasis, and anticholinergic effects (falls and delirium risk).
• Movement symptoms and tardive dyskinesia screening.
• Palpitations, presyncope/syncope, or new dizziness prompt urgent reassessment (label/clinical).

Adverse Effects

Interactions

• Extensive contraindicated combinations due to QTc prolongation and/or increased exposure. Label highlights CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) and multiple QT-prolonging drugs as contraindicated (label).
• The label describes avoiding use in known CYP2D6 poor metabolizers and contraindicates use with several CYP2D6-inhibiting agents (label).
• Avoid combining with other QT-prolonging drugs when possible; correct electrolyte abnormalities and reassess ECG risk factors (label/clinical).
• Additive sedation and hypotension can occur with alcohol, opioids, benzodiazepines, and other sedatives (clinical).

Other Useful Information

• When QT risk is the limiting factor, compare views can help identify alternatives with lower QT burden and/or available LAI formulations for adherence (APA/clinical).

References

1. Thioridazine hydrochloride tablets prescribing information — DailyMed (2025)
2. Torsade de Pointes (StatPearls) — StatPearls Publishing (NCBI Bookshelf) (2025)
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)