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Systematic (IUPAC) name
CAS number 50-52-2
ATC code N05AC02
PubChem 5452
DrugBank APRD00596
Chemical data
Formula C21H26N2S2 
Mol. mass 370.577
Pharmacokinetic data
Bioavailability incomplete
Metabolism hepatic
Half life 7–13 hours (up to 20 hours)
Excretion feces
Therapeutic considerations
Pregnancy cat.

Only if clearly needed

Legal status

RX-only-medication, non-narcotic

Routes oral (tablets, concentration, sometimes syrup)

Thioridazine is a piperidine antipsychotic drug previously widely used in the treatment of schizophrenia and psychosis. It is available from various companies under the names Mellaril, Novorizadine, and Thioril. Due to concerns about cardiotoxicity and retinopathy at high doses this drug is prescribed less than previously. A serious side effect is the potentially fatal neuroleptic malignant syndrome. It exerts its actions through a central adrenergic-blocking, a dopamine-blocking and minor anticholinergic blocking activity.



Previous additional indications were agitated depression, tension and anxiety linked to alcohol withdrawal and dysphoria of epileptic patients. It had even (Melleretten in Europe) an indication for the treatment of psychosis in children and adolescents (10mg to 60mg daily).

It was also given off-label for the treatment of insomnia and for alleviation of opiate withdrawal.

Thioridazine is known to kill multidrug-resistant mycobacterium tuberculosis and MRSA at clinical concentrations.[1]


Thioridazine is a racemic compound with two enantiomers, both of which are metabolized, according to Eap et al, by CYP2D6 into (S)- and (R)-thioridazine 2-sulfoxide, better known as mesoridazine,[2] and into (S)- and (R)-thioridazine-5-sulfoxide.[3] Mesoridazine is in turn metabolized into sulforidazine.[4] Thioridazine is an inhibitor of CYP1A2 and CYP3A2[5]

Side effects

For further information see: Phenothiazine

The most commonly complained about side effect is the agonizing akathisia which is the main reason for low patient compliance

Tardive dyskinesia characterized by involuntary movements of the lips, mouth, and tongue can be long lasting or irreversible. Neuroleptic malignant syndrome is potentially fatal.

Central nervous system side-effects occur. These are mainly drowsiness, dizziness, fatigue, and vertigo. Early and late extrapyramidal side-effects are seen only infrequently (less than 1% altogether). There is no clear dose-effect relationship, as with higher doses anticholinergic effects of thioridazine become more prominent.

Thioridazine causes also an unusual high incidence of impotence and anorgasmia due to a strong alpha-blocking activity. Painful ejaculation or no ejaculation at all is also sometimes seen.

Autonomous side-effects (dry mouth, urination-difficulties, obstipation, induction of glaucoma, postural hypotension, and sinus tachycardia) occur obviously less often than with most other mildly potent antipsychotics.

Thioridazine is no longer recommended as first-line treatment due its side-effect of prolonging the QT interval on the EKG. Thioridazine-5-sulfoxide is responsible for the ventricular tachycardia, torsades de pointes according to Heath, Svensson and Martensson.[6]

Also, the serious and sometimes fatal blood damage agranulocytosis is seen more frequently (approximately 1/500 to 1/1,000 patients) with thioridazine than with other typical phenothiazines (1/2,000 to 1/10,000 patients).

Thioridazine if given over a prolonged time and in high doses can be stored in the ocula and the retina of the eyes and in the heart muscle. Clinical consequences (disturbed or blurred vision) are rare.


It is advisable to withdraw thioridazine gradually and not abruptly to avoid unpleasant withdrawal symptoms (agitation, insomnia, anxiety). Another neuroleptic may be introduced to the therapeutic regime step by step (overlapping), if needed. If sudden withdrawal of thioridazine is necessary, withdrawal symptoms can also be alleviated with the benzodiazepines lorazepam (Ativan) 1mg—2mg, alprazolam (Xanax) 0,5mg prn or clonazepam (Klonopin) 0,5mg to 2mg prn (as needed) for up to 2 weeks (not longer to avoid addiction).


The manufacturer Novartis/Sandoz/Wander of the brands of thioridazine, Mellaril in the USA and Canada and Melleril in Europe, discontinued the drug worldwide in June 2005.

The usual dosage was 50mg per day for mild cases to 600–800 mg per day for severely disturbed patients.

Thioridazine may still be available from other manufacturers as a generic drug with the precaution that it is used only in psychotic patients refractory to other forms of drug treatment. ECG-monitoring and frequent white blood cell counts are required before initiating therapy and in close intervals afterwards.

References and end notes

  • PubChem Substance Summary: Thioridazine National Center for Biotechnology Information,.
  • Antipsychotic Mellaril Removed from Market Schizophrenia Daily News Blog.
  1. ^ Amaral L, Viveiros M, Molnar J. "Antimicrobial activity of phenothiazines."
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Thioridazine". A list of authors is available in Wikipedia.
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