Thioridazine

MELLARIL

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What it isLow-potency first-generation antipsychotic blocking D2, H1, muscarinic, alpha-1, and hERG channels; refractory schizophrenia.

Why this oneLower EPS than with high-potency typicals could not offset its unusually unfavorable cardiac and retinal safety profile.

What limits itQT prolongation and torsades demand ECG and CYP2D6 review; high exposure can cause irreversible retinal pigmentation.

FDA-approved for

schizophrenia (~1962)

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Dose-related QTc prolongation associated with Torsades de pointes and sudden death — reserve for schizophrenia refractory to other antipsychotics. Increased mortality in elderly patients with dementia-related psychosis (not approved for this use).

FDA dosing	Population	Start	Target	Max
Schizophrenia (refractory to other antipsychotics)	Adults	50–100 mg TID	200–800 mg/day divided BID–QID	800 mg/day
Schizophrenia (refractory) in pediatric patients	Pediatric	0.5 mg/kg/day in divided doses	Titrate to optimum effect	3 mg/kg/day

Renal Undefined

Hepatic Undefined

Maximum 800 mg/day (adults); 3 mg/kg/day (pediatric)

Instructions

Reserve for patients who fail other antipsychotics due to QTc/Torsades risk
Individualize to the smallest effective dose
Avoid with QTc-prolonging drugs and with CYP2D6 inhibitors
After control, reduce gradually to minimum maintenance dose

Contraindications

Concomitant use with other QTc-prolonging drugs; congenital long QT syndrome or history of cardiac arrhythmias
Drugs that inhibit CYP2D6 (e.g., fluoxetine, paroxetine, fluvoxamine, propranolol, pindolol), and patients who are CYP2D6 poor metabolizers
Severe CNS depression or comatose states from any cause (including drug-induced)
Hypertensive or hypotensive heart disease of extreme degree

Cautions

QTc prolongation, Torsades de pointes, sudden death
Increased mortality in elderly patients with dementia-related psychosis
Tardive dyskinesia
Neuroleptic malignant syndrome
Extrapyramidal symptoms
Sedation
Hyperprolactinemia / endocrine effects
Pigmentary skin-eye changes with long-term use

Adverse reactions

Drowsiness
Extrapyramidal symptoms / pseudoparkinsonism
Dry mouth
Blurred vision
Constipation
Galactorrhea / breast engorgement / amenorrhea
QTc prolongation

Pregnancy Third-trimester exposure risks neonatal extrapyramidal/withdrawal symptoms; use only if potential benefit justifies potential fetal risk

Lactation Undefined

⚠ BOXED WARNINGS

QT prolongation and torsades de pointes
Increased mortality in elderly patients with dementia-related psychosis

Cost, est. cash$10–$300/month

Generic entry1983

Classes and tags

Clinical profile

Therapeutic safety burden2 / 4

Overdose danger2 / 4

Weight-gain liability3 / 4

Sedation liability3 / 4

QT / Torsades4 / 4

Direct muscarinic antagonism3 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryC

Defining liabilityMetabolic effects, extrapyramidal symptoms/tardive dyskinesia and agent-specific QT or orthostatic risk.

Mechanism of action: Thioridazine ballicule

Thioridazine ballicule: receptor binding, kinetics and half-life diagram

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Memory aids: mascots and interaction avatars

Thioridazine MELLARIL mascot mnemonic cartoon — **“Mellow & Tired daze”**
Spooky mascot → antipsychotic
Polka dots on pink → α1 blocker → syncope if titrated too quickly (hit the floor)
QT prolongation

CYP2D6 substrate

Open Thioridazine in the interactive console ↗