thioridazine MELLARIL

Class: First Generation Antipsychotic/​Phenothiazine
FDA Indications: Schizophrenia
Off-Label Use:
Forms: 10, 15, 25, 50, 100, 150, 200 mg tablet; 30 and 100 mg/mL po soln
Dose Range: 200-800 mg/day
Starting: 50-100 mg tid; increase gradually; maximum 800 mg/day in divided doses
Stopping: Taper 6-8 weeks, rapid d/c can lead to rebound psychosis

NAMI drug fact sheet

Contraindications: QTc ≥ 450 msec or if taking an agent capable of significantly prolonging QTc (e.g., pimozide, selected antiarrhythmics, moxifoxacin, and sparfloxacin); if there is a h/o QTc prolongation or cardiac arrhythmia, recent acute myocardial infarction, uncompensated heart failure
in patients with suspected or established subcortical brain damage, in patients receiving large doses of hypnotics, and in comatose or severely depressed states. Phenothiazines are contraindicated with significant hepatic impairment.
Serious Side Effects: , , , BLACK BOX: Cardiac Arrhythmias, Neutropenia and/or Agranulocytosis (rare), Hyperprolactinemia, Neuroleptic-Induced Deficit Syndrome
Known Risk of TdP
Side Effects: EPS, priapism, akathisia, galactorrhea, amenorrhea, anticholinergic side effects, weight gain, sexual dysfunction, pigmentary retinopathy
1° MOA: Dopamine 2 (D2) receptor antagonism in mesolimbic area
Target: D2 (very high), 5HT2A (very high), α1 (very high), H1 (high), M1 (moderate-high)
t½: 24 (6-40)° TMAX:
Substrate of: 2D6; 1A2, 3A4
Inhibits: ∅ ; Induces:
Active Metabolites: mesoridazine
  • - may enhance QTc prolongation of other drugs capable of prolonging QTc interval
  • - 2D6 inhibitors can ↑ serum levels; 2D6 inducers can ↓ serum levels
  • - caution when coprescribing with other CNS depressants
  • - low potency FGA
  • - the branded product, Mellaril, was withdrawn worldwide in 2005 because it caused severe cardiac arrhythmias
  • - prolongs the QTc interval in a dose-dependent manner
  • - the benefits of thioridazine do not outweigh its risks for most patients
  • - because of its effects on the QTc interval, thioridazine is not intended for use unless other options (at least 2 antipsychotics) have failed
  • - causes less extrapyramidal symptoms than some other conventional antipsychotics
  • - Thioridazine is known to kill XDR-TB and to make MRSA sensitive to β-lactam antibiotics
Special Populations

Category C—The limited human pregnancy data and the absence of relevant animal data prevents a better assessment of the embryo-fetal risk. Nevertheless, most of the evidence for the phenothiazine agents suggest that these drugs are low risk. However, use of antipsychotic drugs during the 3rd trimester can cause extrapyramidal and/ or withdrawal symptoms in the newborn.

No reports describing the use of thioridazine during human lactation have been located. It is not known if the drug is excreted into breast milk, but the molecular weight (about 407) suggests that it will be present in breast milk. Moreover, other phenothiazines are present in milk and have caused toxicity. Sedation is a possible effect in nursing infants.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic function, concomitant disease or other drug therapy.

2019 BEE℞S Recommendation: Avoid, except in schizophrenia or bipolar disorder. Increased risk of CVA and greater rate of cognitive decline and mortality in persons with dementia. Avoid antipsychotics for behavioral problems of dementia or delirium unless nonpharmacological options have failed or are not possible and the older adult is threatening substantial harm to self or others.

No dosage adjustment necessary.

Use with caution in patients with hepatic impairment.


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Last updated February 29 2024 20:54:18. Disclaimer: This website does not provide medical advice, nor is it a substitute for clinical judgment.