Side Effects of thioridazine: A Synthesis of Findings from 25 Studies

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Original Abstract of the Article

Major Research Findings

Thioridazine is an antipsychotic drug that has been used for decades, but it can cause a number of serious side effects, including fatal poisoning, photosensitivity, heart problems, and a range of other effects. 4 9 10

Although thioridazine is known for its adverse effects, it has also been studied as a potential treatment for multidrug-resistant tuberculosis due to its antimycobacterial properties. 16 20 Researchers have even developed new derivatives of thioridazine with reduced toxicity and enhanced antimycobacterial activity. 7 14 5

Reasons for Side Effects

Thioridazine's side effects are likely caused by its interactions with various cellular processes, including the disruption of mitochondrial function and the inhibition of calcium channels. 18 1 21

Common Side Effects

Photosensitivity

Thioridazine can cause a skin reaction to sunlight, leading to rashes and burns. 9 25

Heart Problems

Thioridazine can cause heart rhythm problems, potentially leading to sudden death. 10 19

Hematologic Effects

Thioridazine has been linked to a decrease in blood cell counts, which can lead to infections and other health problems. 24

Neurological Effects

Thioridazine can cause a range of neurological side effects, including muscle stiffness, tremors, and extrapyramidal symptoms. 12

Sexual Side Effects

Thioridazine can cause sexual dysfunction, including retrograde ejaculation. 8 11

Side Effect Countermeasures

Photosensitivity

Patients should be informed about the risk of photosensitivity and advised to wear protective clothing and sunscreen. 9

Heart Problems

Individuals with pre-existing heart conditions or those at risk for heart problems should avoid thioridazine. 10

Hematologic Effects

Regular blood monitoring is crucial for individuals taking thioridazine. 24

Comparison between Studies

Commonalities in Studies

Most studies agree that thioridazine can cause a range of side effects, including photosensitivity, heart problems, and neurological issues.

Differences in Studies

Studies have varied in the frequency and severity of reported side effects. This may be influenced by factors such as the dosage of thioridazine, the individual patient's susceptibility, and the presence of other medical conditions.

Precautions for Application to Real Life

Individuals taking thioridazine should be aware of the potential risks and take precautions to minimize side effects. This includes avoiding sunlight, informing doctors of any pre-existing heart conditions, and undergoing regular blood monitoring.

Limitations of Current Research

Research on the long-term effects of thioridazine is still limited. Further investigation is needed to fully understand the long-term consequences of thioridazine use.

Future Research Directions

Future research should focus on understanding the mechanisms underlying thioridazine's side effects and developing safer alternatives or approaches to mitigate its adverse effects. 6

Conclusion

Thioridazine is a powerful antipsychotic, but it has a significant potential for serious side effects. While it shows promise for treating multidrug-resistant tuberculosis, the risks need to be weighed carefully against the potential benefits. Patients should be thoroughly informed about the potential risks and carefully monitored during treatment. 22

Literature analysis of 25 papers
Positive Content
11
Neutral Content
4
Negative Content
10
Article Type
0
0
1
7
25
1.

Calcium channel blockade: possible explanation for thioridazine's peripheral side effects.

Author: GouldR J, MurphyK M, ReynoldsI J, SnyderS H

Cardiac effects
Sexual side effects

Thioridazine, an antipsychotic drug, possesses calcium antagonist activity, which may relate to its cardiac and sexual side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

2.

Efficacy and side effects of nitrazepam and thioridazine as sleeping aids in psychogeriatric in-patients.

Author: LinnoilaM, ViukariM

Effective for insomnia
Impairs mobility and daily activities

Thioridazine was found to be a suitable sleeping aid for psychogeriatric patients, with a longer sleep duration compared to placebo. Nitrazepam, however, impaired patients' ability to move and conduct everyday activities.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Controlled Clinical TrialA clinical trial that evaluates the effectiveness of a treatment by comparing a group that receives the intervention with a group that receives a placebo or standard treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

5.

A Novel Derivative of Thioridazine Shows Low Toxicity and Efficient Activity against Gram-Positive Pathogens.

Author: JørgensenNadia S, SaabyLasse, AnderssonAnne M, KromannSofie, SheikhsamaniEhsan, PerminAnders, RoncoTroels, SvenningsenSøren W, ChristensenJørn B, OlsenRikke H

Antimicrobial efficacy
Low toxicity

A less toxic thioridazine derivative, designated T5, exhibited low blood-brain barrier permeability and reduced the minimal inhibitory concentration (MIC) against *Staphylococcus aureus* by 32-fold compared to thioridazine HCl.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

6.

Antitubercular polyhalogenated phenothiazines and phenoselenazine with reduced binding to CNS receptors.

Author: NiziMaria Giulia, DesantisJenny, NakataniYoshio, MassariSerena, MazzarellaMaria Angela, ShetyeGauri, SabatiniStefano, BarrecaMaria Letizia, ManfroniGiuseppe, FelicettiTommaso, Rushton-GreenRowena, HardsKiel, LataczGniewomir, SatałaGrzegorz, BojarskiAndrzej J, CecchettiVioletta, KolářMichal H, HandzlikJadwiga, CookGregory M, FranzblauScott G, TabarriniOriana

Anti-TB activity
Reduced CNS side-effects
Off-target effects

New anti-tuberculosis (TB) drugs are needed. This study focused on phenothiazines (PTZs), which are known inhibitors of an essential enzyme in Mycobacterium tuberculosis (Mtb). The study aimed to overcome the limitations of PTZs for TB treatment by modifying their structure. The researchers developed new PTZs with improved anti-TB activity and reduced side effects, specifically targeting the central nervous system.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

8.

Retrograde ejaculation associated with quetiapine and treatment with low-dose imipramine.

Author: RoughleyMatthew, LyallMarc

Quetiapine treatment
RE treatment
Sexual side-effects

This case report describes a 25-year-old man who developed retrograde ejaculation (RE) during treatment with quetiapine, a commonly used antipsychotic. RE improved with low-dose imipramine, suggesting a potential treatment option for antipsychotic-associated RE.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

10.

Drug-induced QT Interval Prolongation in the Intensive Care Unit.

Author: EtchegoyenCecilia Villa, KellerGuillermo Alberto, MradSebastian, ChengSixuan, Di GirolamoGuillermo

Drug-induced LQTS

This study addresses drug-induced QT interval prolongation, the most common acquired cause of Long QT syndrome (LQTS), which is characterized by an extended duration of the ventricular repolarization. This syndrome increases the risk for polymorphic ventricular tachycardia and sudden death.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

12.

Clozapine-related extrapyramidal side effects: a case report.

Author: GalloMariana, SquarcioneChiara, BersaniFrancesco Saverio, MinichinoAmedeo, FojanesiMarta, BiondiMassimo

Clozapine
EPS risk

Clozapine is a medication used to treat schizophrenia. While it is generally considered to have fewer side effects than other antipsychotic medications, this case report shows that long-term use can still lead to extrapyramidal side effects, which are movement problems.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

13.

Thioridazine enhances sensitivity to carboplatin in human head and neck cancer cells through downregulation of c-FLIP and Mcl-1 expression.

Author: SeoSeung Un, ChoHyuk Ki, MinKyoung-Jin, WooSeon Min, KimShin, ParkJong-Wook, KimSang Hyun, ChoiYung Hyun, KeumYoung Sam, HyunJin Won, ParkHyun Ho, LeeSang-Han, KimDong Eun, KwonTaeg Kyu

Apoptosis induction
Cancer treatment

This study investigated the synergistic effect of carboplatin and thioridazine on apoptosis in cancer cells. The findings suggest that the combination treatment induces apoptosis through proteasomal degradation of Mcl-1 and c-FLIP, highlighting a potential new therapeutic strategy for cancer treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Effect of thioridazine on antioxidant status of HEMn-DP melanocytes.

Author: OtrębaMichał, BeberokArtur, WrześniokDorota, RokJakub, BuszmanEwa

Melanin inhibition
Oxidative stress
Thioridazine toxicity

Thioridazine is an antipsychotic drug that can induce serious side effects, including extrapyramidal symptoms, ocular disorders, and skin disorders. This study showed that thioridazine induces oxidative stress in melanocytes and inhibits melanogenesis, which may explain its side effects on pigmented tissues.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Cytotoxicity of phenothiazine derivatives associated with mitochondrial dysfunction: a structure-activity investigation.

Author: de FariaPriscila A, BettaninFernanda, CunhaRodrigo L O R, Paredes-GameroEdgar J, Homem-de-MelloPaula, NantesIseli L, RodriguesTiago

Cytotoxic activity
Hepatotoxicity

This study investigated the effects of five phenothiazine derivatives on the viability of liver cells. All derivatives were found to be toxic to cells, with thioridazine exhibiting the highest toxicity. The findings suggest that the mitochondrial permeability transition may be involved in phenothiazine-induced cell death.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

20.

Potential antimicrobial agents for the treatment of multidrug-resistant tuberculosis.

Author: AlsaadNoor, WilffertBob, van AltenaRichard, de LangeWiel C M, van der WerfTjip S, KosterinkJos G W, AlffenaarJan-Willem C

Drug repurposing
MDR-TB treatment
Drug toxicity

This review explores the potential use of six drugs with antimicrobial activity against Mycobacterium tuberculosis, including co-trimoxazole and thioridazine, as potential candidates for the treatment of multidrug-resistant (MDR) tuberculosis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

21.

Molecular mechanisms of pharmaceutical drug binding into calsequestrin.

Author: SubraArun K, NissenMark S, LewisKevin M, MuralidharanAshwin K, SanchezEmiliano J, MiltingHendrik, KangChul Hee

Caffeine antagonism
Epigallocatechin antagonism
Cardiotoxicity

Calsequestrin (CASQ) is a protein found in muscles that helps store calcium. CASQ can bind to various drugs known to cause muscle toxicity. This study identified three binding sites on CASQ that may explain how drugs like daunomycin, doxorubicin, thioridazine, and trifluoperazine cause muscle problems. The study also suggests that caffeine and epigallocatechin, natural compounds, may block these binding sites and potentially reduce drug toxicity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

22.

Potential therapy of multidrug-resistant and extremely drug-resistant tuberculosis with thioridazine.

Author: AmaralLeonard, MolnarJoseph

Treats XDRTB
Serious side effects

The study proposes the use of thioridazine, a phenothiazine neuroleptic, for the treatment of extremely drug-resistant tuberculosis (XDRTB) in patients with AIDS. While thioridazine has serious side effects, the high mortality associated with XDRTB makes its use a viable option. A specific protocol for thioridazine treatment is provided.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

23.

Thioridazine induces apoptosis of multidrug-resistant mouse lymphoma cells transfected with the human ABCB1 and inhibits the expression of P-glycoprotein.

Author: SpenglerGabriella, MolnarJoseph, ViveirosMiguel, AmaralLeonard

Cancer treatment
Side effects

Thioridazine (TZ), a phenothiazine neuroleptic, was studied for activity against multidrug-resistant (MDR) cancer cells and the overexpressed ABCB1 transporter (P-glycoprotein) that is the cause for the MDR phenotype of these cancer cells.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

25.

Drug-induced photosensitivity: culprit drugs, management and prevention.

Author: DruckerAaron M, RosenCheryl F

Photosensitivity

This review discusses the diagnosis, prevention, and management of drug-induced photosensitivity. The diagnosis is based on drug history and the appearance of the eruption. The main management strategy is prevention, including patient education and sun protection.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

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