Thioridazine is a first-generation (typical) phenothiazine antipsychotic agent, specifically a piperidine derivative. It is a potent dopamine D2 receptor antagonist with significant anticholinergic and alpha-1 adrenergic blocking properties. Historically used for schizophrenia and severe agitation, its use in India is now severely restricted due to a well-established risk of dose-related, potentially fatal cardiac arrhythmias (torsades de pointes) caused by significant QTc interval prolongation. It is now primarily indicated for the short-term management of severe behavioral problems in children and for resistant, disabling psychoses in adults where other therapies have failed, under strict cardiac monitoring.
Adult: Schizophrenia: Initial: 50-100 mg daily in 2-3 divided doses. Maintenance: 200-800 mg daily in 2-3 divided doses. MAXIMUM: 800 mg/day. MUST BE TITRATED SLOWLY WITH ECG MONITORING.
Note: Administer orally with or without food to minimize GI upset. Can be administered with food if nausea occurs. The tablet should be swallowed whole with a glass of water. Avoid alcohol and grapefruit juice. Regular ECG monitoring (baseline, after dose changes, and periodically during therapy) is MANDATORY.
Exerts its antipsychotic effect primarily through post-synaptic antagonism of dopamine D2 receptors in the mesolimbic pathway of the brain. Its significant anticholinergic (muscarinic receptor blockade) and alpha-1 adrenergic blockade contribute to its side effect profile and differentiate it from other phenothiazines. The QTc prolongation is due to blockade of the rapid component of the delayed rectifier potassium current (IKr) in cardiac myocytes.
Pregnancy: Category C: Animal studies show adverse effects. No adequate human studies. Use only if potential benefit justifies potential fetal risk. Risk of EPS or withdrawal symptoms in neonate if used in third trimester. Generally contraindicated.
Driving: Severely impairs alertness, coordination, and reaction time. Patients must be warned not to drive or operate heavy machinery, especially during initial therapy and dose adjustments.
| Fluoxetine, Paroxetine | Potent CYP2D6 inhibition → drastically increased thioridazine levels, severe QTc prolongation, cardiac toxicity. | Contraindicated |
| Quinidine, Procainamide, Amiodarone, Sotalol | Additive QTc prolongation → high risk of torsades de pointes. | Contraindicated |
| Macrolides (Clarithromycin, Erythromycin), Fluoroquinolones (Moxifloxacin) | Additive QTc prolongation. | Contraindicated/Avoid |
| Other CNS Depressants (Alcohol, Opioids, Benzodiazepines) | Additive CNS and respiratory depression. | Major |
| Antihypertensives | Potentiation of hypotensive effects. | Major |
| Anticholinergic drugs (Trihexyphenidyl, Atropine, TCAs) | Additive anticholinergic side effects (ileus, hyperthermia, confusion). | Moderate |
| Levodopa | Mutual antagonism of effects. | Moderate |