Thioridazine

Thioridazine is a phenothiazine antipsychotic used in the treatment of schizophrenia and other psychotic disorders. Developed in the 1950s and marketed as Mellaril, it is considered a classical or typical antipsychotic in the phenothiazine subclass.

It acts primarily as a dopamine D2 receptor antagonist in the mesolimbic pathway, helping to reduce psychotic symptoms. As with other phenothiazines, it also blocks alpha-adrenergic, histaminergic, and muscarinic receptors, contributing to sedation, hypotension, and anticholinergic effects.

Thioridazine is highly lipophilic with extensive tissue distribution. It is metabolized in the liver to active metabolites, including mesoridazine. Elimination is primarily hepatic, and the drug has a long and variable half-life requiring careful dose titration.

Clinical use and regulation: Historically used for schizophrenia and related conditions, thioridazine use has declined because of safety concerns. It is generally not a first-line treatment and is reserved for patients who have not responded to other antipsychotics, with benefits weighed against risks and with close monitoring.

Adverse effects and safety: The drug carries a notable risk of extrapyramidal symptoms and sedation, along with anticholinergic effects and orthostatic hypotension. Of particular concern are ocular toxicities, including retinal pigmentary changes and corneal deposits with long-term use, and cardiac risks such as QT interval prolongation that can lead to torsades de pointes, especially at high doses or with interacting medications.

Regulatory status: Due to ocular and cardiac risks, thioridazine use has declined and many guidelines restrict its duration and require monitoring. It remains a rare, second- or third-line option in some countries.

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