Thioridazine

Uses

Thioridazine is used 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 also used to associated treatment for these conditions: Psychosis, Schizophrenia

How Thioridazine works

Thioridazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; blocks alpha-adrenergic effect, depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.

Dosage

Thioridazine dosage

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 optimumtherapeuticeffect is obtained or the maximum dose of 3 mg/kg/day has been reached.

Side Effects

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.

Toxicity

LD₅₀=956-1034 mg/kg (Orally in rats); Agitation, blurred vision, coma, confusion, constipation, difficulty breathing, dilated or constricted pupils, diminished flow of urine, dry mouth, dry skin, excessively high or low body temperature, extremely low blood pressure, fluid in the lungs, heart abnormalities, inability to urinate, intestinal blockage, nasal congestion, restlessness, sedation, seizures, shock

Precaution

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.

Interaction

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

Food Interaction

• Avoid alcohol. Ingesting alcohol may potentiate the CNS depressant actions of thioridazine.

Thioridazine Alcohol interaction

[Moderate] GENERALLY AVOID:

Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment.

Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines.

The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

Patients should be advised to avoid alcohol during phenothiazine therapy.

Thioridazine Drug Interaction

Major: citalopram, escitalopram, fluoxetine, risperidone, quetiapine, ondansetronModerate: aripiprazole, amphetamine / dextroamphetamine, zolpidem, divalproex sodium, ginkgo, gabapentin, alprazolamUnknown: calcium / vitamin d, atorvastatin, acetaminophen, levothyroxine, acetaminophen, cyanocobalamin, cholecalciferol

Thioridazine Disease Interaction

Major: dementia, acute alcohol intoxication, cardiovascular disease, CNS depression, head injury, QT interval prolongationModerate: anticholinergic effects, breast cancer, dystonic reactions, hematologic toxicity, liver disease, NMS, parkinsonism, renal dysfunction, respiratory disorders, seizure disorders, tardive dyskinesia

Elimination Route

60%

Half Life

21-25 hours

Pregnancy & Breastfeeding use

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.

Contraindication

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.

Special Warning

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

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

Acute Overdose

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.

Storage Condition

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

Innovators Monograph

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