Thioridazine

Mechanism-of-action classes: Adrenergic alpha-Antagonists; Cytochrome P450 Inhibitors; Dopamine Antagonists.

• Thioridazine hydrochloride tablets are indicated for the management of schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs. Due to the risk of significant, potentially life threatening, proarrhythmic effects with thioridazine treatment, thioridazine hydrochloride tablets should be used only in patients who have failed to respond adequately to treatment with appropriate courses of other antipsychotic drugs, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs.

• Thioridazine hydrochloride tablet use should be avoided in combination with other drugs that are known to prolong the QTc interval and in patients with congenital long QT syndrome or a history of cardiac arrhythmias. Reduced cytochrome P450 2D6 isozyme activity drugs that inhibit this isozyme (e.g., fluoxetine and paroxetine) and certain other drugs (e.g., fluvoxamine, propranolol, and pindolol) appear to appreciably inhibit the metabolism of thioridazine.contraindicated

Since thioridazine hydrochloride tablets are associated with a dose related prolongation of the QTc interval, which is a potentially life threatening event, its use should be reserved for schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs. Dosage must be individualized and the smallest effective dosage should be determined for each patient (see INDICATIONS and WARNINGS ). Adults The usual starting dose for adult schizophrenic patients is 50 mg to 100 mg three times a day, with a gradual increment to a maximum of 800 mg daily if necessary. Once effective control of symptoms has been achieved, the dosage may be reduced gradually to determine the minimum maintenance dose. The total daily dosage ranges from 200 mg to 800 mg, divided into two to four doses. Pediatric Patients For pediatric patients with schizophrenia who are unresponsive to other agents, the recommended initial dose is 0.5 mg/kg/day given in divided doses. Dosage may be increased gradually until optimum therapeutic effect is obtained or the maximum dose of 3 mg/kg/day has been reached.

Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Thioridazine hydrochloride is not approved for the treatment of patients with dementia-related psychosis (see ). Potential for Proarrhythmic Effects DUE TO THE POTENTIAL FOR SIGNIFICANT, POSSIBLY LIFE THREATENING, PROARRHYTHMIC EFFECTS WITH THIORIDAZINE TREATMENT, THIORIDAZINE SHOULD BE RESERVED FOR USE IN THE TREATMENT OF SCHIZOPHRENIC PATIENTS WHO FAIL TO SHOW AN ACCEPTABLE RESPONSE TO ADEQUATE COURSES OF TREATMENT WITH OTHER ANTIPSYCHOTIC DRUGS, EITHER BECAUSE OF INSUFFICIENT EFFECTIVENESS OR THE INABILITY TO ACHIEVE AN EFFECTIVE DOSE DUE TO INTOLERABLE ADVERSE EFFECTS FROM THOSE DRUGS. CONSEQUENTLY, BEFORE INITIATING TREATMENT WITH THIORIDAZINE, IT IS STRONGLY RECOMMENDED THAT A PATIENT BE GIVEN AT LEAST TWO TRIALS, EACH WITH A DIFFERENT ANTIPSYCHOTIC DRUG PRODUCT, AT AN ADEQUATE DOSE, AND FOR AN ADEQUATE DURATION. THIORIDAZINE HAS NOT BEEN SYSTEMATICALLY EVALUATED IN CONTROLLED TRIALS IN THE TREATMENT OF REFRACTORY SCHIZOPHRENIC PATIENTS AND ITS EFFICACY IN SUCH PATIENTS IS UNKNOWN. A crossover study in nine healthy males comparing single doses of thioridazine 10 mg and 50 mg with placebo demonstrated a dose related prolongation of the QTc interval. The mean maximum increase in QTc interval following the 50 mg dose was about 23 msec; greater prolongation may be observed in the clinical treatment of unscreened patients.

In the recommended dosage ranges with thioridazine hydrochloride most side effects are mild and transient. Central Nervous System Drowsiness may be encountered on occasion, especially where large doses are given early in treatment. Generally, this effect tends to subside with continued therapy or a reduction in dosage. Pseudoparkinsonism and other extrapyramidal symptoms may occur but are infrequent. Nocturnal confusion, hyperactivity, lethargy, psychotic reactions, restlessness, and headache have been reported but are extremely rare. Autonomic Nervous System Dryness of mouth, blurred vision, constipation, nausea, vomiting, diarrhea, nasal stuffiness, and pallor have been seen. Endocrine System Galactorrhea, breast engorgement, amenorrhea, inhibition of ejaculation, and peripheral edema have been described. Skin Dermatitis and skin eruptions of the urticarial type have been observed infrequently. Photosensitivity is extremely rare. Cardiovascular System Thioridazine produces a dose related prolongation of the QTc interval, which is associated with the ability to cause Torsades de pointes type arrhythmias, a potentially fatal polymorphic ventricular tachycardia, and sudden death (see WARNINGS ). Both Torsades de pointes type arrhythmias and sudden death have been reported in association with thioridazine. A causal relationship between these events and thioridazine therapy has not been established but, given the ability of thioridazine to prolong the QTc interval, such a relationship is possible.

Pregnancy Nonteratogenic Effects Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Thioridazine hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Many of the symptoms observed are extensions of the side effects described under ADVERSE REACTIONS . Thioridazine can be toxic in overdose, with cardiac toxicity being of particular concern. Frequent ECG and vital sign monitoring of overdosed patients is recommended. Observation for several days may be required because of the risk of delayed effects. Signs and Symptoms Effects and clinical complications of acute overdose involving phenothiazines may include: Cardiovascular: Cardiac arrhythmias, hypotension, shock, ECG changes, increased QT and PR intervals, non-specific ST and T wave changes, bradycardia, sinus tachycardia, atrioventricular block, ventricular tachycardia, ventricular fibrillation, Torsades de pointes, myocardial depression. Central Nervous System: Sedation, extrapyramidal effects, confusion, agitation, hypothermia, hyperthermia, restlessness, seizures, areflexia, coma. Autonomic Nervous System: Mydriasis, miosis, dry skin, dry mouth, nasal congestion, urinary retention, blurred vision. Respiratory: Respiratory depression, apnea, pulmonary edema. Gastrointestinal: Hypomotility, constipation, ileus. Renal: Oliguria, uremia.

• Aug 30, 1983ANDAANDA088134Chartwell Rx
• Aug 30, 1983ANDAANDA088133Chartwell Rx
• Aug 30, 1983ANDAANDA088131Chartwell Rx
• Nov 18, 1983ANDAANDA088004Mylan
• Nov 20, 1984ANDAANDA088135Chartwell Rx
• Oct 7, 1988ANDAANDA089953Sun Pharm Industries

1. 1Weight Increased917%
2. 2Drug Ineffective713%
3. 3Dyspnoea713%
4. 4Dystonia611%
5. 5Hyperglycaemia611%
6. 6Hypoxia611%
7. 7Malaise611%
8. 8Muscle Spasms611%
9. 9Pruritus611%
10. 10Psychotic Disorder611%
11. 11Tinnitus611%
12. 12Toxicity To Various Agents611%
13. 13Abdominal Distension59.4%
14. 14Abdominal Pain59.4%
15. 15Akathisia59.4%

Recent PubMed references pinned to Thioridazine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Simultaneous Determination of Thioridazine and Its Metabolites by UHPLC-MS/MS With Application to a Pharmacokinetic Study in Rats.
  Biomedical chromatography : BMC · 2026 · Moon KS, Song JM, Ahn SH, et al.
  PMID 41392592DOI 10.1002/bmc.70298
• Thioridazine induces phospholipid accumulation and necroptosis in parental and tamoxifen-resistant breast cancer cells.
  Molecular omics · 2025 · Mythri C, Jorvekar SB, Suraj N, et al.
  PMID 40719011DOI 10.1039/d5mo00039d
• A thioridazine-derived molecule exhibits potential anti-inflammatory activity through IKK inhibition.
  Inflammopharmacology · 2025 · Sarup S, Atre R, Obukhov AG, et al.
  PMID 40504323DOI 10.1007/s10787-025-01786-y
• Thioridazine Induces Increase in Expression of the Pyruvate Transporter MPC1 Associated with Immune Infiltration in Malignant Tumors.
  Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2025 · Bogomolova EA, Murashko MM, Stasevich EM, et al.
  PMID 39920561DOI 10.1134/S001249662460060X
• Identification of host antioxidant effectors as thioridazine targets: Impact on cardiomyocytes infection and Trypanosoma cruzi-induced acute myocarditis.
  Biochimica et biophysica acta. Molecular basis of disease · 2024 · Liz Belli Cassa Domingues E, Gonçalves-Santos E, Santana Caldas I, et al.
  PMID 38806073DOI 10.1016/j.bbadis.2024.167264
• Thioridazine reverses trastuzumab resistance in gastric cancer by inhibiting S-phase kinase associated protein 2-mediated aerobic glycolysis.
  World journal of gastroenterology · 2023 · Yang ZY, Zhao YW, Xue JR, et al.
  PMID 38130998DOI 10.3748/wjg.v29.i45.5974
• In Vitro and In Vivo Antileishmanial Activity of Thioridazine.
  Acta parasitologica · 2024 · Sifontes-Rodríguez S, Mollineda-Diogo N, Monzote-Fidalgo L, et al.
  PMID 38070122DOI 10.1007/s11686-023-00746-2
• Repurposing thioridazine for inducing immunogenic cell death in colorectal cancer via eIF2α/ATF4/CHOP and secretory autophagy pathways.
  Cell communication and signaling : CCS · 2023 · Tran TH, Kao M, Liu HS, et al.
  PMID 37488534DOI 10.1186/s12964-023-01190-5

The 10 most recently updated of 11 ClinicalTrials.gov registrations naming Thioridazine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Assess Stroke Risk Among Users of Typical Versus Atypical Antipsychotics Stratified by Broad Age Group
  Completed · Observational · 1,234,412 enrolled · Janssen Research & Development, LLC
  NCT04002700updated 2025-06-25
• Antipsychotic Induced Structural and Functional Brain Changes
  Terminated · Phase 4 · Interventional · 174 enrolled · RWTH Aachen University
  NCT02435095updated 2020-11-25
• Family Intervention in Recent Onset Schizophrenia Treatment (FIRST)
  Completed · Observational · 296 enrolled · Janssen Scientific Affairs, LLC
  NCT02600741updated 2019-01-23
• Reducing Antipsychotic-Induced Weight Gain in Children With Metformin
  Completed · Phase 1 · Interventional · 96 enrolled · Nationwide Children's Hospital
  NCT01231074updated 2019-01-02
• Evaluation of the Necessity of Long-term Pharmacological Treatment With Antipsychotics in Schizophrenic Patients
  Completed · Phase 4 · Interventional · 21 enrolled · Technical University of Munich
  NCT02307396updated 2018-10-11
• Pharmacovigilance in Gerontopsychiatric Patients
  Terminated · Phase 3 · Interventional · 407 enrolled · Hannover Medical School
  NCT02374567updated 2018-02-28
• YouScript IMPACT Registry
  Completed · Observational · 800 enrolled · Genelex Corporation
  NCT02191358updated 2017-03-01
• Safety Study of Thioridazine in Combination With Cytarabine to Treat Relapsed or Refractory Acute Myeloid Leukemia
  Completed · Phase 1 · Interventional · 13 enrolled · Ontario Clinical Oncology Group (OCOG)
  NCT02096289updated 2016-12-07
• Feasibility of Thioridazine as a Mobilizing Agent for CD34+ Hematopoietic Progenitor Cells
  Terminated · Early phase 1 · Interventional · 6 enrolled · New Mexico Cancer Research Alliance
  NCT01765803updated 2016-04-14
• Antipsychotics and Risk of Hyperglycemic Emergencies
  Completed · Observational · 725,489 enrolled · Canadian Network for Observational Drug Effect Studies, CNODES
  NCT02582736updated 2015-10-21

CPIC-curated drug–gene pairs for Thioridazine. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• CYP2D6CPIC B/C (provisional)ClinPGx 3FDA label: Actionable PGx

Frequently asked questions

How does Thioridazine work?

Mechanism-of-action classes: Adrenergic alpha-Antagonists; Cytochrome P450 Inhibitors; Dopamine Antagonists.

What is Thioridazine used for?

According to FDA labeling, Thioridazine carries indications including: Thioridazine hydrochloride tablets are indicated for the management of schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs. Due to the risk of significant, potentially life threatening, proarrhythmic effects with thioridazine treatment, thioridazine hydrochloride tablets should be used only in patients who have failed to respond adequately to treatment with appropriate courses of other antipsychotic drugs, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Thioridazine?

Thioridazine is classified as Phenothiazines with piperidine structure, Phenothiazine, Adrenergic alpha-Antagonists, Cytochrome P450 Inhibitors, Dopamine Antagonists, Decreased Central Nervous System Organized Electrical Activity, Decreased Dopamine Activity, Decreased Norepinephrine Activity, Hypothalamic Endocrine Activity Alteration.

What are the contraindications for Thioridazine?

Thioridazine labeling lists contraindications including: Thioridazine hydrochloride tablet use should be avoided in combination with other drugs that are known to prolong the QTc interval and in patients with congenital long QT syndrome or a history of cardiac arrhythmias. Reduced cytochrome P450 2D6 isozyme activity drugs that inhibit this isozyme (e.g., fluoxetine and paroxetine) and certain other drugs (e.g., fluvoxamine, propranolol, and pindolol) appear to appreciably inhibit the metabolism of thioridazine.. Always consult the full prescribing information and a clinician.