Side Effects of Mellaril (thioridazine)

What is Mellaril (thioridazine)?

Mellaril (thioridazine) is an antipsychotic used to manage schizophrenia. Thioridazine is one of the older, first-generation antipsychotic medications. 

Although the exact mechanism of antipsychotics is unknown, scientists believe they may work by blocking the action of the neurotransmitter dopamine in the brain. Mellaril is used when patients do not respond to other antipsychotics. The brand name Mellaril is discontinued. 

Common side effects of Mellaril include: 

Serious side effects of Mellaril include:

Drug interactions of Mellaril include medications such as procainamide, sotalol, amiodarone, and dofetilide that affect heart rate and rhythm, which can cause abnormal heart beats. 

Antidepressants such as fluoxetine, sertraline, and tricyclic antidepressants may reduce the breakdown of Mellaril, leading to increased side effects of Mellaril.

Mellaril should be used with caution with medications that depress the central nervous system and cause sedation or drowsiness such as:

Such combinations can cause:

  • excessive sedation,
  • drowsiness,
  • weakness,
  • confusion,
  • speech impairment, and
  • in severe cases coma or death.

Combining alcohol with Mellaril also increases the risk of low blood pressure.

Use of Mellaril during pregnancy has not been adequately studied. Infants exposed to antipsychotics during the third trimester of pregnancy are at risk for extrapyramidal and withdrawal symptoms after birth.

Safe use of Mellaril by nursing mothers has not been established. Consult your doctor before breastfeeding

What are the important side effects of Mellaril (thioridazine)?

Thioridazine causes extrapyramidal side effects such as:

  • Abnormal muscle contractions
  • Difficulty breathing and swallowing
  • Neck spasms

Other side effects include:

Mellaril (thioridazine) side effects list for healthcare professionals

In the recommended dosage ranges with Mellaril (thioridazine HCl) most side effects are mild and transient.

Central Nervous System: Drowsiness may be encountered on occasion, especially where large doses are given early in treatment. Generally, this effect tends to subside with continued therapy or a reduction in dosage. Pseudoparkinsonism and other extrapyramidal symptoms may occur but are infrequent. Nocturnal confusion, hyperactivity, lethargy, psychotic reactions, restlessness, and headache have been reported but are extremely rare.

Autonomic Nervous System: Dryness of mouth, blurred vision, constipation, nausea, vomiting, diarrhea, nasal stuffiness, and pallor have been seen.

Endocrine System: Galactorrhea, breast engorgement, amenorrhea, inhibition of ejaculation, and peripheral edema have been described.

Skin: Dermatitis and skin eruptions of the urticarial type have been observed infrequently. Photosensitivity is extremely rare.

Cardiovascular System: Mellaril (thioridazine hcl) produces a dose related prolongation of the QTc interval, which is associated with the ability to cause torsade de pointes-type arrhythmias, a potentially fatal polymorphic ventricular tachycardia, and sudden death. Both torsade de pointes-type arrhythmias and sudden death have been reported in association with Mellaril (thioridazine hcl) . A causal relationship between these events and Mellaril (thioridazine hcl) therapy has not been established but, given the ability of Mellaril (thioridazine hcl) to prolong the QTc interval, such a relationship is possible. Other ECG changes have been reported (see Phenothiazine Derivatives: Cardiovascular Effects).

Other: Rare cases described as parotid swelling have been reported following administration of Mellaril (thioridazine hcl) .

Post Introduction Reports

These are voluntary reports of adverse events temporally associated with Mellaril (thioridazine hcl) that were received since marketing, and there may be no causal relationship between Mellaril (thioridazine hcl) use and these events: priapism.

Phenothiazine Derivatives

It should be noted that efficacy, indications, and untoward effects have varied with the different phenothiazines. It has been reported that old age lowers the tolerance for pheno-thiazines. The most common neurological side effects in these patients are parkinsonism and akathisia. There appears to be an increased risk of agranulocytosis and leukopenia in the geriatric population. The physician should be aware that the following have occurred with one or more phenothiazines and should be considered whenever one of these drugs is used:

Autonomic Reactions: Miosis, obstipation, anorexia, paralytic ileus.

Cutaneous Reactions: Erythema, exfoliative dermatitis, contact dermatitis.

Blood Dyscrasias: Agranulocytosis, leukopenia, eosinophilia, thrombocytopenia, anemia, aplastic anemia, pancytopenia.

Allergic Reactions: Fever, laryngeal edema, angioneurotic edema, asthma.

Hepatotoxicity: Jaundice, biliary stasis.

Cardiovascular Effects: Changes in the terminal portion of the electrocardiogram to include prolongation of the QT interval, depression and inversion of the T wave, and the appearance of a wave tentatively identified as a bifid T wave or a U wave have been observed in patients receiving phenothiazines, including Mellaril (thioridazine hcl) . To date, these appear to be due to altered repolarization, not related to myocardial damage, and reversible. Nonetheless, significant prolongation of the QT interval has been associated with serious ventricular arrhythmias and sudden death. Hypotension, rarely resulting in cardiac arrest, has been reported.

Extrapyramidal Symptoms: Akathisia, agitation, motor restlessness, dystonic reactions, trismus, torticollis, opisthotonus, oculogyric crises, tremor, muscular rigidity, akinesia.

Tardive Dyskinesia: Chronic use of neuroleptics may be associated with the development of tardive dyskinesia.

The syndrome is characterized by involuntary choreoathetoid movements which variously involve the tongue, face, mouth, lips, or jaw (e.g., protrusion of the tongue, puffing of cheeks, puckering of the mouth, chewing movements), trunk, and extremities. The severity of the syndrome and the degree of impairment produced vary widely.

The syndrome may become clinically recognizable either during treatment, upon dosage reduction, or upon withdrawal of treatment. Movements may decrease in intensity and may disappear altogether if further treatment with neuroleptics is withheld. It is generally believed that reversibility is more likely after short rather than long-term neuroleptic exposure. Consequently, early detection of tardive dyskinesia is important. To increase the likelihood of detecting the syndrome at the earliest possible time, the dosage of neuroleptic drug should be reduced periodically (if clinically possible) and the patient observed for signs of the disorder. This maneuver is critical, for neuroleptic drugs may mask the signs of the syndrome.

Neuroleptic Malignant Syndrome (NMS): Chronic use of neuroleptics may be associated with the development of Neuroleptic Malignant Syndrome. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias).

Endocrine Disturbances: Menstrual irregularities, altered libido, gynecomastia, lactation, weight gain, edema. False positive pregnancy tests have been reported.

Urinary Disturbances: Retention, incontinence.

Others: Hyperpyrexia. Behavioral effects suggestive of a paradoxical reaction have been reported. These include excitement, bizarre dreams, aggravation of psychoses, and toxic confusional states. More recently, a peculiar skin-eye syndrome has been recognized as a side effect following long-term treatment with phenothiazines. This reaction is marked by progressive pigmentation of areas of the skin or conjunctiva and/or accompanied by discoloration of the exposed sclera and cornea. Opacities of the anterior lens and cornea described as irregular or stellate in shape have also been reported. Systemic lupus erythematosus-like syndrome.

What drugs interact with Mellaril (thioridazine)?

Reduced cytochrome P450 2D6 isozyme activity, drugs which inhibit this isozyme (e.g., fluoxetine and paroxetine), and certain other drugs (e.g., fluvoxamine, propranolol, and pindolol) appear to appreciably inhibit the metabolism of thioridazine. The resulting elevated levels of thioridazine would be expected to augment the prolongation of the QTc interval associated with Mellaril (thioridazine hcl) and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsade de pointes-type arrhythmias.

Such an increased risk may result also from the additive effect of co-administering Mellaril (thioridazine hcl) with other agents that prolong the QTc interval. Therefore, Mellaril (thioridazine hcl) is contraindicated with these drugs as well as in patients, comprising about 7% of the normal population, who are known to have a genetic defect leading to reduced levels of activity of P450 2D6.

Drugs that Inhibit Cytochrome P450 2D6

In a study of 19 healthy male subjects, which included 6 slow and 13 rapid hydroxylators of debrisoquin, a single 25 mg oral dose of thioridazine produced a 2.4-fold higher Cmax and a 4.5-fold higher AUC for thioridazine in the slow hydroxylators compared to rapid hydroxylators. The rate of debrisoquin hydroxylation is felt to depend on the level of cytochrome P450 2D6 isozyme activity. Thus, this study suggests that drugs that inhibit P450 2D6 or the presence of reduced activity levels of this isozyme will produce elevated plasma levels of thioridazine. Therefore, the co-administration of drugs that inhibit P450 2D6 with Mellaril (thioridazine hcl) and the use of Mellaril (thioridazine hcl) in patients known to have reduced activity of P450 2D6 are contraindicated.

Drugs that Reduce the Clearance of Mellaril (thioridazine hcl) through Other Mechanisms

Fluvoxamine: The effect of fluvoxamine (25 mg b.i.d. for one week) on thioridazine steady state concentration was evaluated in 10 male in-patients with schizophrenia. Concentrations of thioridazine and its two active metabolites, mesoridazine and sulforidazine, increased three-fold following co-administration of fluvoxamine. Fluvoxamine and Mellaril (thioridazine hcl) should not be co-administered.

Propranolol: Concurrent administration of propranolol (100-800 mg daily) has been reported to produce increases in plasma levels of thioridazine (approximately 50%-400%) and its metabolites (approximately 80%-300%). Propranolol and Mellaril (thioridazine hcl) should not be co-administered.

Pindolol: Concurrent administration of pindolol and thioridazine have resulted in moderate, dose-related increases in the serum levels of thioridazine and two of its metabolites, as well as higher than expected serum pindolol levels. Pindolol and Mellaril (thioridazine hcl) should not be co-administered.

Drugs That Prolong the QTc Interval

There are no studies of the co-administration of Mellaril (thioridazine hcl) and other drugs that prolong the QTc interval. However, it is expected that such co-administration would produce additive prolongation of the QTc interval and, thus, such use is contraindicated.


Mellaril (thioridazine) is an antipsychotic used to manage schizophrenia. The brand name Mellaril is discontinued. Common side effects of Mellaril include extrapyramidal side effects (such as abnormal muscle contractions, difficulty breathing and swallowing, and neck spasms), low blood pressure, constipation, dry mouth, blurred vision, seizures, dizziness, drowsiness, urinary retention, worsening of glaucoma, and increased or decreased blood glucose. Mellaril should be used with caution with medications that depress the central nervous system and cause sedation or drowsiness such as alprazolam, clonazepam, zolpide, codeine, morphine, and alcohol. Use of Mellaril during pregnancy has not been adequately studied. Infants exposed to antipsychotics during the third trimester of pregnancy are at risk for extrapyramidal and withdrawal symptoms after birth. Safe use of Mellaril by nursing mothers has not been established.

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