Thioridazine has been shown to prolong the QTc interval in a dose related manner, and drugs with this potential, including thioridazine, have been associated with Torsades de pointes type arrhythmias and sudden death. Due to its potential for significant, possibly life threatening, proarrhythmic effects, thioridazine should be reserved for use in the treatment of schizophrenic patients who fail to show an acceptable response to adequate courses of treatment with other antipsychotic drugs, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs (see WARNINGS, CONTRAINDICATIONS, and INDICATIONS).
Increased Mortality in Elderly Patients with Dementia-Related Psychosis
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Thioridazine hydrochloride is not approved for the treatment of patients with dementia-related psychosis (see WARNINGS).
Thioridazine hydrochloride is 2-methylmercapto-10-[2-(N-methyl-2-piperidyl) ethyl] phenothiazine.
Thioridazine hydrochloride tablets are 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 hydrochloride tablets 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 hydrochloride tablets, it is strongly recommended that a patient be given at least two trials, each with a different antipsychotic drug product, at an adequate dose, and for an adequate duration (see WARNINGS and CONTRAINDICATIONS).
However, the prescriber should be aware that thioridazine hydrochloride tablets have not been systematically evaluated in controlled trials in treatment refractory schizophrenic patients and its efficacy in such patients is unknown.
Media Articles Related to Thioridazine
Clozapine Best Antipsychotic for Schizophrenia?
Source: Medscape Psychiatry & Mental Health Headlines [2016.07.21]
Real-world observational data suggest clozapine is the most effective and quetiapine is the least effective in schizophrenia.
Medscape Medical News
Evista Blunts Symptoms in Women With Schizophrenia
Source: MedPage Today OB/Gyn [2016.07.21]
(MedPage Today) -- No safety issues in small study, but thromboembolic risk remains concern
Clozapine shows better efficacy in children with schizophrenia than in adults
Source: Psychology / Psychiatry News From Medical News Today [2016.07.13]
Childhood-onset schizophrenia is a rare, severe, and difficult to treat form of the disease, but a new study suggests that children show a stronger response to clozapine than to other antipsychotic...
Analysis of genetic repeats suggests role for DNA instability in schizophrenia
Source: Schizophrenia News From Medical News Today [2016.06.24]
Variations in the number of DNA sequence repeats are known to exist between individuals.
European Commission approves TREVICTA (paliperidone palmitate 3-monthly injection), for schizophrenia
Source: Schizophrenia News From Medical News Today [2016.06.02]
Janssen has announced that the European Commission (EC) has approved the use of TREVICTA® (paliperidone palmitate, a 3-'monthly injection) for the maintenance treatment of schizophrenia.
Published Studies Related to Thioridazine
Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses. [2007.11]
We compared the effects of single doses of thioridazine and mesoridazine on the heart rate-corrected QT (QTc) interval in healthy adult volunteers. QTc intervals and plasma concentrations of thioridazine, mesoridazine, and metabolites were measured after single oral doses of thioridazine hydrochloride 50 mg, mesoridazine besylate 50 mg, or placebo in a double-blind, crossover study...
Repeated dosing with donepezil does not affect the safety, tolerability or pharmacokinetics of single-dose thioridazine in young volunteers. [2004.11]
AIM: To investigate the effects of donepezil at steady state on the safety, tolerability and pharmacokinetics of a single dose of thioridazine, in healthy subjects... CONCLUSIONS: Repeated dosing with donepezil, 5 mg daily for 2 weeks, had no significant effect on the safety, tolerability or pharmacokinetics of thioridazine. Thioridazine was poorly tolerated.
Effect of fluoxetine and imipramine on the pharmacokinetics and tolerability of the antipsychotic quetiapine. [2002.04]
The effects of fluoxetine and imipramine on the pharmacokinetics and nonpsychiatric side effect profile of quetiapine fumarate were investigated in 26 patients with schizophrenia, schizoaffective disorder, or bipolar disorder in a multicenter, two-period, multiple-dose, open-label, randomized trial.
Psychomotor effects of zaleplon and thioridazine coadministration. [2000.06]
OBJECTIVE: To assess the potential pharmacokinetic and pharmacodynamic interaction of zaleplon and thioridazine administered concomitantly in healthy volunteers... CONCLUSION: The results of single-dose administration showed an additive pharmacodynamic interaction between zaleplon and thioridazine at 1 h in one of four tests and supra-additivity for 4 h in another test. This interaction is relatively short in duration due to the short half-life of zaleplon.
Withdrawal of haloperidol, thioridazine, and lorazepam in the nursing home: a controlled, double-blind study. [1999.08.09]
BACKGROUND: Ongoing regimens of haloperidol, thioridazine, and lorazepam are commonly administered to manage behavior problems in nursing home residents. Nevertheless, there is controversy over whether periodic drug withdrawal should be attempted when those medications are prescribed. This study addressed that issue by examining the effects of discontinuing treatment with haloperidol, thioridazine, and lorazepam among residents of a large suburban nursing home... CONCLUSIONS: Results of this work suggest that longterm use of haloperidol, thioridazine, and lorazepam in nursing homes to manage agitation should be closely monitored for their efficacy. Furthermore, routine attempts at drug withdrawal should be considered for most residents taking psychotropic medication.
Clinical Trials Related to Thioridazine
Feasibility of Thioridazine as a Mobilizing Agent for CD34+ Hematopoietic Progenitor Cells [Terminated]
This study will investigate the possibility of using the drug thioridazine (also called
Mellaril) to increase the number of certain types of cells moving from the bone marrow to
the circulation in a group of healthy humans. The types of cells we hope to collect are
called CD34+ progenitor, or stem cells. These cells can be used in the laboratory to better
understand a number of diseases and suggest new strategies for therapy. Perhaps the most
important potential application of human stem cells is the generation of cells and tissues
that could be used for cell-based therapies, as a renewable source of replacement cells and
tissues to treat diseases including Alzheimer's diseases, spinal cord injury, stroke, burns,
heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.
Safety Study of Thioridazine in Combination With Cytarabine to Treat Relapsed or Refractory Acute Myeloid Leukemia [Recruiting]
This is a Phase I trial investigating the safety of using thioridazine in addition to
cytarabine in elderly patients with relapsed or refractory Acute Myeloid Leukemia.
Changes in Heart Rhythms Associated With Antipsychotic Drug Treatment [Completed]
This study is being done to look at the electrical activity of the heart. This study will
help decide whether taking recordings for a 24-hour period gives more useful information
than recording it for a few seconds in a doctor's office. The study will compare 24 hour
electrocardiogram (ECG) results of patients taking thioridazine (Mellaril) to those of other
patients taking different medications that took part in another study.
Pharmacovigilance in Gerontopsychiatric Patients [Recruiting]
The purpose of this multicenter-study is to investigate safety of psychopharmacological
treatment and rates of adverse drug reactions in gerontopsychiatric inpatients. Elderly
people are at higher risk for developing side effects under pharmacological treatment due to
an altered metabolic situation, higher comorbidity rates and often polypharmacy. Furthermore
gerontopsychiatric patients can often not articulate their symptoms clearly, for example due
to pronounced cognitive impairment.
The aim of the study is to gain valid data of possible adverse drug reaction rates, their
potential risk factors and outcome, as well as medical prescription practises.
To assess these outcomes an intensive pharmacovigilance-monitoring will be conducted at the
five participating study sites.
At Baseline demographic data, previous and present disorders, use of drugs, previous and
present medication, quality of life, cognitive function, physical examination results,
laboratory results and ECG will be assessed.
Afterwards patients are visited weekly and screened for possible adverse drug reactions. All
adverse drug reactions will be coded in the MedDRA-system.
In case of a possible serious adverse drug reaction serum levels of all psychotropic
substances applicated will be assessed. Drug combinations will be analysed using an
established advanced bioinformatic tool (mediQ). Diagnosis, medication intake and possible
adverse drug reactions are documented continually.
2 weeks after discharge from the ward, patients will be contacted by phone to assess
Evaluation of the Necessity of Long-term Pharmacological Treatment With Antipsychotics in Schizophrenic Patients [Recruiting]
The main objective of the trial is to evaluate, how long an antipsychotic relapse-prevention
should be continued and to which time a patient with schizophrenia is protected enough, so
that a withdrawal or reduction of the medication seems appropriate. Relapse is defined as
Page last updated: 2016-07-21