Thioridazine


Article Author:
Shana Feinberg


Article Editor:
Abdolreza Saadabadi


Editors In Chief:
Zina Clark
Barbara Simmons


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
2/4/2019 4:12:12 PM

Indications

Similar to other first generation, or typical, antipsychotics, thioridazine is a medication used to treat schizophrenia. Other indications for use include other psychotic disorders, depressive disorders, pediatric behavioral disorders, and geriatric psychoneurotic manifestations.[1][2][3][4]

Mechanism of Action

Typical antipsychotics, including thioridazine work to treat psychosis by blocking dopamine (D2) receptors. These medications are effective in treating the positive symptoms of schizophrenia, such as hallucinations, delusions, and disorganization. Atypical antipsychotics, also called second-generation antipsychotics, are known to treat both the positive and negative symptoms of schizophrenia. Some negative symptoms include apathy, low energy, and flat affect.

Administration

Thioridazine is taken as an oral medication in tablet form. The tablets come in either 10 mg, 25 mg, 50 mg, or 100 mg, and the maximum dose is up to 800 mg per day. For schizophrenia, it is recommended to initiate thioridazine at 50 mg to -100mgs three times per day and gradually increase the dose as indicated. For depressive disorders, it is recommended to start the dose at 25 mg three times a day and increase up to 200 mg per day.

Adverse Effects

Extrapyramidal Side Effects (EPS)

Similar to other antipsychotics, taking thioridazine comes with a risk of EPS. In general, first-generation antipsychotics are associated more with EPS, which is why this is an important side effect to understand when prescribing thioridazine. EPS includes symptoms of dystonia, parkinsonism, akathisia, and tardive dyskinesia. Dystonic reactions are muscle spasms that may occur early on and involve the eyes, tongue, or neck, and it can be treated with either benztropine or diphenhydramine. It is important to monitor patients for dystonia to avoid problems breathing, such as laryngospasm, which may require intubation. Parkinson disease is associated with low levels of dopamine, and it leads to several symptoms, including but not limited to resting tremor, cogwheel rigidity, postural instability, and shuffling gait. Therefore, it would make sense that dopamine-blocking antipsychotics, such as thioridazine, would cause similar symptoms as Parkinson disease, which are called parkinsonism effects. Akathisia is a side effect, which is described as restlessness. Parkinsonism can also be treated with benztropine or diphenhydramine, and benzodiazepines or beta-blockers may be used to treat akathisia. Tardive dyskinesia is even more associated with typical antipsychotics and is associated with prolonged use of the medication. The abnormal (choreoathetoid) movements seen in patients with tardive dyskinesia can occur in the region of the head, tongue, or face, and this is a serious side effect because it may not be reversed, unlike the other EPS symptoms. If a patient has tardive dyskinesia, the best treatment would be to stop the antipsychotic medication and try an atypical antipsychotic with less risk, such as clozapine.[5][6][7]

Neuroleptic Malignant Syndrome (NMS) 

NMS is another serious side effect of all antipsychotics and is associated more with typical antipsychotics. This adverse effect may occur suddenly, and the provider should look for unstable vital signs, such as tachycardia and fever, muscle rigidity, and elevated white blood cell count and creatinine phosphokinase. NMS should be treated with hydration and supportive therapy, and it is important to stop the antipsychotic medication. If necessary, other treatments include dopamine agonists, dantrolene or bromocriptine.

ECG Changes

Thioridazine, like many antipsychotics, is associated with prolonged QTc intervals, which may have serious or fatal consequences, such as Torsades de pointes. It is recommended that patients with known prolonged QTc or arrhythmias avoid thioridazine. Prior to starting this medication, it would be wise to order an ECG and monitor for QTc prolongation or other ECG changes during treatment.

Other Side Effects

Patients may have nonspecific symptoms while taking thioridazine, such as dry mouth, dry eyes, sedation, weight gain, dizziness, erectile dysfunction, pruritus, photosensitivity, and constipation. Other rare and more unique side effects of thioridazine include irreversible retinal pigmentation, poikilothermia, and agranulocytosis.

Contraindications

There is a black-box warning for dementia-related psychosis because it may increase the risk of death secondary to either cardiovascular or infectious effect. Thioridazine is associated with a prolonged QT interval. Thus patients with long QT syndrome, QT intervals prolonged to more than 450, or taking other drugs that prolong the QT interval should avoid thioridazine. Also, patients with known heart arrhythmias or hypotensive or hypertensive heart disease should also avoid this medication.

Patients taking other medications should be evaluated before using thioridazine. Medications that may affect thioridazine levels include but are not limited to fluoxetine, paroxetine, duloxetine, fluvoxamine, propranolol, and pindolol.

Although a rare, but serious side effect of thioridazine is agranulocytosis, each patient should be evaluated for abnormal white blood cell counts before use because this medication may exacerbate this problem.

Monitoring

Patients should be monitored for medication side effects during treatment, and it is often necessary to screen patients before treatment to obtain baseline results. Since thioridazine can cause significant ECG (electrocardiogram) changes and arrhythmias, it is important to get a baseline ECG and potassium level. Furthermore, an additional ECG is recommended for any change in dose and periodically after that. Another side effect of this typical antipsychotic is low white blood cell counts, which indicates a complete blood count (CBC) to be ordered, especially if the patient has a history of abnormal white blood cell counts. Thioridazine can cause irreversible retinal pigmentation over time. Thus a patient should get an ophthalmologic exam if the patient is taking the medication for a prolonged period of time. Since thioridazine is a pregnancy category C medication, it may be advised to get a pregnancy test before administration of the drug. Thioridazine must be cautioned for use in the third trimester of pregnancy, as it may be associated with a risk of neonatal withdrawal symptoms and extrapyramidal side effects. Furthermore, thioridazine has a narrow therapeutic index, which means it is necessary to monitor each patient for adverse side effects carefully.[8][9]

Toxicity

Thioridazine is a low potency typical antipsychotic, like chlorpromazine. Thus these medications can be dosed in the hundreds of milligrams. Unlike higher potency antipsychotics, thioridazine has a lower incidence of extrapyramidal side effects. However, lower potency antipsychotics are more likely to be associated with antimuscarinic, antihistaminic, and antiadrenergic side effects. Thioridazine is metabolized through the liver with a half-life of 24 hours and is excreted in the urine, bile, and feces. The hepatic cytochrome P450 CYP2D6 metabolism of thioridazine is important because it is used to identify different drug-drug interactions. Thus, it is necessary to evaluate patients and identify medications that may increase or decrease levels of thioridazine. Also, there are no antidotes to thioridazine, so it is important to avoid overdose.

Enhancing Healthcare Team Outcomes

The use of thioridazine has declined significantly because of the availability of safer and more effective atypical antipsychotics. However, healthcare workers including the primary care provider or nurse practitioner who prescribe thioridazine should first consult with the psychiatrist for a better option. If the drug is prescribed, its adverse effects must be closely monitored. Further, the patient must be educated about the side effects and potential drug interactions. Although a rare, but serious side effect of thioridazine is agranulocytosis, each patient should be evaluated for abnormal white blood cell counts before use because this medication may exacerbate this problem.


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Thioridazine - Questions

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Which of the following is not an effect of thioridazine?



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Which psychotropic drug has the most anticholinergic side effects?



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Ocular pigmentation and retinal deposits are caused by which antipsychotic agent?



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Which antipsychotic has the strongest association with prolongation of the QT interval?



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Which urological side effect is associated with thioridazine?



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Which of the following antipsychotic medications is most likely to cause arrhythmias and QT interval prolongation?



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A schizophrenic patient is seen in the eye clinic. The patient was referred to the eye clinic because of visual complaints. On exam, there is pigmentation of the anterior lens capsule. This could have resulted after the administration of what medication?



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Which of the following medications is most likely to cause a Parkinson-like reaction?



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What EKG abnormality is most associated with thioridazine?



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What exam is recommended after long-term use of thioridazine?



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Thioridazine - References

References

Thioridazine 2006;     [PubMed]
Mesoridazine 2006;     [PubMed]
Drobnis EZ,Nangia AK, Psychotropics and Male Reproduction. Advances in experimental medicine and biology. 2017;     [PubMed]
Adams SA,Nasrallah HA, Multiple retinal anomalies in schizophrenia. Schizophrenia research. 2018 May;     [PubMed]
Euwema MS,Swanson TJ, Deadly Single Dose Agents 2018 Jan;     [PubMed]
Dean L, Thioridazine Therapy and {i}CYP2D6{/i} Genotypes 2012;     [PubMed]
Tisdale JE, Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Canadian pharmacists journal : CPJ = Revue des pharmaciens du Canada : RPC. 2016 May;     [PubMed]
Kristiansen JE,Dastidar SG,Palchoudhuri S,Roy DS,Das S,Hendricks O,Christensen JB, Phenothiazines as a solution for multidrug resistant tuberculosis: From the origin to present. International microbiology : the official journal of the Spanish Society for Microbiology. 2015 Mar;     [PubMed]
Xiang YT,Chiu HF,Ungvari GS,Correll CU,Lai KY,Wang CY,Si TM,Lee EH,He YL,Yang SY,Chong MY,Kua EH,Fujii S,Sim K,Yong MK,Trivedi JK,Chung EK,Udomratn P,Chee KY,Sartorius N,Tan CH,Shinfuku N, QTc prolongation in schizophrenia patients in Asia: clinical correlates and trends between 2004 and 2008/2009. Human psychopharmacology. 2015 Mar;     [PubMed]

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