Thioridazine

Thioridazine is indicated for the management of schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs. Due to the risk of significant, potentially life-threatening, proarrhythmic effects with thioridazine treatment, thioridazine should be used only in patients who have failed to respond adequately to treatment with appropriate courses of other antipsychotic drugs, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs. Consequently, before initiating treatment with thioridazine, it is strongly recommended that a patient be given at least 2 trials, each with a different antipsychotic drug product, at an adequate dose, and for an adequate duration.

However, the prescriber should be aware that thioridazine has not been systematically evaluated in controlled trials in treatment refractory schizophrenic patients and its efficacy in such patients is unknown.

Thioridazine is a piperidine phenothiazine which blocks postsynaptic mesolimbic dopaminergic receptors in the brain. It exhibits a strong α-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones.

Since thioridazine is associated with a dose-related prolongation of the QTc interval, which is a potentially life-threatening event, its use should be reserved for schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs. Dosage must be individualized and the smallest effective dosage should be determined for each patient 

Adults: The usual starting dose for adult schizophrenic patients is 50 to 100 mg three times a day, with a gradual increment to a maximum of 800 mg daily if necessary. Once effective control of symptoms has been achieved, the dosage may be reduced gradually to determine the minimum maintenance dose. The total daily dosage ranges from 200 to 800 mg, divided into two to four doses.

Pediatric: For pediatric patients with schizophrenia who are unresponsive to other agents, the recommended initial dose is 0.5 mg/kg/day given in divided doses. Dosage may be increased gradually until optimum therapeutic effect is obtained or the maximum dose of 3 mg/kg/day has been reached.

May potentiate the effects of CNS depressants (e.g. anaesth, barbiturates, narcotics, opiates, other psychoactive drugs).

Patients with reduced levels of CYP2D6 isoenzyme, congenital long QT syndrome or history of cardiac arrhythmias; severe CNS depression or comatose states of any cause; hypertensive or hypotensive heart disease of extreme degree. Concomitant use with drugs that prolong QTc interval, CYP2D6 isoenzyme inhibitors and drugs which reduce thioridazine clearance by other mechanisms.

Tardive dyskinesia; leucopenia, neutropenia, agranulocytosis; drowsiness, pseudoparkinsonism and other extrapyramidal symptoms; dry mouth, blurred vision, constipation, nausea, vomiting, diarrhoea, nasal stuffiness, pallor; galactorrhoea, breast engorgement, amenorrhoea, inhibition of ejaculation, peripheral oedema; dermatitis, skin eruptions. Rarely, nocturnal confusion, hyperactivity, lethargy, psychotic reactions, restlessness, headache, photosensitivity, parotid swelling.

Pregnancy Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Patient with severe CV disease, narrow-angle glaucoma, Parkinson's disease, seizure disorder. Avoid abrupt withdrawal. Hepatic and renal impairment. Elderly with dementia-related psychosis. Pregnancy and lactation.

Symptoms: Cardiotoxicity (e.g. prolongation of QT interval and QRS complex).

Management: Symptomatic and supportive treatment with CV (e.g. ECG) monitoring. Establish a patent airway and ensure adequate oxygenation and ventilation. Employ gastric lavage and administer repeated doses of activated charcoal. May include ventricular pacing, defibrillation, admin of IV Mg sulfate, lidocaine, phenytoin or isoproterenol, correction of electrolyte abnormalities and/or acid-base balance to manage arrhythmias. Administer lidocaine with caution as it may increase the risk of developing seizures.

Phenothiazine drugs, Phenothiazine related drugs.

Renal Impairment: Lower initial doses and more gradual dosage increase.
Hepatic Impairment: Lower initial doses and more gradual dosage increase.

Store between 15-30° C. Protect from light.