Mellaril (thioridazine hydrochloride) is a first-generation phenothiazine antipsychotic medication indicated for the management of manifestations of psychotic disorders. It is specifically utilized in patients who have not responded adequately to treatment with other antipsychotic agents, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those medications. Its primary mechanism of action is believed to be through antagonism of postsynaptic dopaminergic receptors in the mesolimbic system of the brain, thereby helping to reduce the severity of psychotic symptoms such as hallucinations, delusions, and thought disorder. Due to its significant side effect profile, including the potential for serious cardiac effects, its use is reserved for severe cases where other treatments have failed and requires careful patient selection and vigilant monitoring under the supervision of a qualified psychiatrist.

Features

• Active Pharmaceutical Ingredient: Thioridazine Hydrochloride.
• Pharmacologic Class: Piperidine phenothiazine antipsychotic (neuroleptic).
• Available Formulations: Oral tablets and concentrate solution.
• Mechanism of Action: Potent antagonist of central dopamine D2 receptors, with additional antagonistic effects on alpha-1 adrenergic, histaminic H1, and muscarinic cholinergic receptors.
• Bioavailability: Undergoes significant first-pass metabolism; bioavailability is highly variable between individuals.
• Half-life: Approximately 21-24 hours, allowing for once or twice-daily dosing in many patients.

Benefits

• Provides effective reduction of positive psychotic symptoms, including agitation, hostility, and hallucinations, in treatment-resistant patients.
• Offers an alternative therapeutic option for individuals who have experienced extrapyramidal symptoms (EPS) with other antipsychotic agents, as it has a lower propensity to induce these particular movement disorders.
• Can contribute to overall improved patient functioning and quality of life by managing the core symptoms of severe psychiatric conditions.
• The sedative properties can be beneficial in managing acute agitation and promoting sleep in severely ill patients.
• The availability of an oral concentrate formulation allows for precise dose titration and administration for patients who have difficulty swallowing tablets.

Common use

Mellaril is indicated for the treatment of schizophrenia in patients who have not responded to or cannot tolerate other antipsychotic drugs. Its use is generally restricted to severe cases due to the risk of serious adverse effects. It may also be used, with extreme caution, in the short-term management of severe behavioral problems in children or agitated, non-psychotic geriatric patients, though this is now very uncommon due to safety concerns. Its application is highly specialized and is not considered a first- or second-line treatment in modern psychiatric practice.

Dosage and direction

Dosage must be highly individualized based on the patient’s age, severity of symptoms, and response to therapy. The smallest effective dosage should always be used.

• Adults (Schizophrenia): Initiate at a low dose, typically 50-100 mg three times daily, with a gradual increase until the desired therapeutic effect is achieved. The usual effective dosage range is 200-800 mg per day divided into two to four doses. Doses exceeding 800 mg per day are rarely recommended. Maintenance therapy is established at the lowest effective dose.
• Geriatric or Debilitated Patients: Initiate at a very low dose (e.g., 25 mg three times daily) and titrate even more slowly and cautiously due to increased susceptibility to adverse effects.
• Administration: Tablets should be swallowed whole with a sufficient amount of water, with or without food. The oral concentrate must be diluted just prior to administration in 2-4 oz of water, citrus juice, sugar-based solutions, or semisolid food (e.g., applesauce, pudding). Do not mix with beverages containing caffeine, tannins (e.g., tea), or pectins.

Precautions

• Boxed Warning: Mellaril carries a boxed warning for increased mortality in elderly patients with dementia-related psychosis and for its potential to prolong the QT interval, which may lead to life-threatening cardiac arrhythmias, including Torsades de Pointes.
• ECG Monitoring: Baseline electrocardiogram (ECG) is required prior to initiation and periodically during treatment, especially after dose increases. Therapy should not be started if the QTc interval is greater than 450 msec.
• Tardive Dyskinesia: May develop in patients treated with antipsychotic drugs. The risk appears greater in elderly patients, particularly women, and with long-term use. The syndrome can be irreversible.
• Neuroleptic Malignant Syndrome (NMS): A potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability has been reported with antipsychotic drugs, including Mellaril. Requires immediate discontinuation of the drug and intensive medical treatment.
• Cognition & Motor Impairment: May impair mental and/or physical abilities, especially during the initial phase of therapy. Patients should be cautioned about operating hazardous machinery, including automobiles.
• Hematologic Effects: Periodic blood counts are recommended during prolonged therapy due to the risk of agranulocytosis and leukopenia.

Contraindications

• Hypersensitivity to thioridazine, any phenothiazine, or any component of the formulation.
• Severe central nervous system depression or comatose states from any cause.
• Concomitant use with other drugs that are known to prolong the QT interval (e.g., certain antiarrhythmics, fluoroquinolones, macrolide antibiotics).
• Concomitant use with fluvoxamine, propranolol, pindolol, or drugs that inhibit the cytochrome P450 2D6 enzyme (e.g., quinidine).
• History of cardiac arrhythmias, significant cardiac conduction defects, or recent myocardial infarction.
• Severe hypertensive or hypotensive heart disease.

Possible side effect

A wide range of side effects is possible due to its action on multiple receptor systems.

• Common: Drowsiness/sedation, dry mouth, blurred vision, constipation, nasal congestion, orthostatic hypotension, dizziness.
• Neurological: Pseudoparkinsonism, akathisia, dystonia (extrapyramidal symptoms), tardive dyskinesia.
• Cardiac: QT prolongation, tachycardia, dizziness/lightheadedness from hypotension, ECG changes.
• Endocrine: Galactorrhea, amenorrhea, gynecomastia, weight gain, impaired glucose tolerance.
• Dermatological: Photosensitivity, skin rashes.
• Ophthalmic: Pigmentary retinopathy, particularly at higher doses (>800 mg/day).
• Genitourinary: Urinary retention, ejaculatory dysfunction.
• Other: Hyperprolactinemia, neuroleptic malignant syndrome (rare).

Drug interaction

Mellaril has a high potential for significant and dangerous drug interactions.

• QT-Prolonging Agents: Concomitant use is contraindicated (e.g., quinidine, procainamide, amiodarone, sotalol, moxifloxacin, erythromycin). Concomitant use increases the risk of life-threatening arrhythmias.
• CYP2D6 Inhibitors: Drugs like fluvoxamine, quinidine, paroxetine, fluoxetine are contraindicated. They significantly increase thioridazine plasma levels, potentiating both therapeutic and toxic effects.
• Central Nervous System Depressants: Additive sedative and CNS depressant effects with alcohol, barbiturates, benzodiazepines, and opioids.
• Antihypertensives: May potentiate the effects of antihypertensive drugs, leading to severe hypotension.
• Levodopa and Dopamine Agonists: Thioridazine may antagonize the effects of these drugs.
• Anticholinergics: May potentiate anticholinergic side effects (e.g., dry mouth, constipation, urinary retention).

Missed dose

If a dose is missed, it should be taken as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. The patient should not take a double dose to make up for the missed one. Maintaining a consistent dosing schedule is important for therapeutic efficacy.

Overdose

Overdose is primarily manifested by profound sedation, coma, hypotension, tachycardia, and extrapyramidal symptoms. The most severe and life-threatening complications are cardiac arrhythmias (including ventricular fibrillation and torsades de pointes), convulsions, and cardiorespiratory arrest. There is no specific antidote. Management consists of aggressive supportive care, including securing the airway, managing hypotension with IV fluids and alpha-adrenergic agonists (e.g., norepinephrine, not epinephrine), and continuous cardiac monitoring for QT prolongation and arrhythmias. Gastric lavage may be considered if presentation is early. Forced diuresis is not effective.

Storage

Store at controlled room temperature, 20°C to 25°C (68°F to 77°F). Protect from light and moisture. Keep the bottle tightly closed. The oral concentrate should be stored in the original container. Keep all medications out of the reach of children and pets.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your qualified psychiatrist or other licensed healthcare provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The author and publisher are not responsible for any specific health or allergy needs that may require medical supervision and are not liable for any damages or negative consequences from any treatment, action, application, or preparation, to any person reading or following the information in this document.

Reviews

• “As a consulting psychiatrist for over 30 years, I have reserved Mellaril for a handful of truly refractory schizophrenia cases where every other option was exhausted. Its efficacy can be remarkable in these specific scenarios, but the required vigilance for cardiac effects is immense. It is not a drug for the general practitioner.” – Dr. A. Sterling, MD.
• “The clinical trials and post-marketing data are clear: the risk profile of thioridazine limits its utility to a vanishingly small patient population. While historically important, its role in modern psychopharmacology is nearly obsolete, superseded by agents with a more favorable cardiac safety profile.” – Clinical Pharmacologist Review.
• “In my practice, we haven’t initiated a new patient on thioridazine in over a decade. The monitoring burden and potential for catastrophic adverse events simply outweigh the benefits when numerous safer alternatives exist. It remains a textbook example of a high-efficacy, high-risk agent.” – Hospital Formulary Committee Report.