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Thioridazine response

MedGen UID:
450490
Concept ID:
CN078018
Sign or Symptom
Synonym: Mellaril response
Drug:
Thioridazine
MedGen UID:
52724
Concept ID:
C0039943
Pharmacologic Substance
A phenothiazine antipsychotic used in the management of PHYCOSES, including SCHIZOPHRENIA. [from MeSH]
 
Gene (location): CYP2D6 (22q13.2)

Definition

Thioridazine is an antipsychotic used in the treatment of schizophrenia and psychosis. Its use is reserved for patients who have failed to respond to or cannot tolerate other antipsychotics. Thioridazine has been shown to prolong the QT interval (the time taken for the heart ventricles to depolarize and repolarize) in a dose related manner. Drugs with this potential have been associated with the life-threatening ventricular tachycardia, "torsades de pointes". The CYP2D6 enzyme is involved in metabolizing thioridazine. About 7% of the population has reduced enzyme activity because of variants in the CYP2D6 gene. In individuals with low CYP2D6 activity, standard doses of thioridazine may lead to higher drug levels in the plasma, and increase the risk of cardiac arrhythmias. The FDA-approved drug label for thioridazine states that thioridazine is contraindicated in individuals who are known to have reduced levels of CYP2D6 activity. The label also states it is contraindicated to coadminister thioridazine with drugs that inhibit CYP2D6 (e.g., fluoxetine, paroxetine) or inhibit the metabolism of thioridazine (e.g., fluvoxamine, propranolol, and pindolol). [from Medical Genetics Summaries]

Professional guidelines

PubMed

Ries R, Sayadipour A
J Psychiatr Pract 2014 Sep;20(5):338-44. doi: 10.1097/01.pra.0000454778.29433.7c. PMID: 25226194
Alsaad N, Wilffert B, van Altena R, de Lange WC, van der Werf TS, Kosterink JG, Alffenaar JW
Eur Respir J 2014 Mar;43(3):884-97. Epub 2013 Aug 29 doi: 10.1183/09031936.00113713. PMID: 23988774
Srisurapanont M, Kittiratanapaiboon P, Jarusuraisin N
Cochrane Database Syst Rev 2001;(4):CD003026. doi: 10.1002/14651858.CD003026. PMID: 11687172

Curated

DailyMed Drug Label, thioridazine, 2019

DailyMed Drug Label, THIORIDAZINE HYDROCHLORIDE, 2016

Recent clinical studies

Etiology

Ren X, Chen X, Zhang X, Jiang S, Zhang T, Li G, Lu Z, Zhang D, Wang S, Qin C
Front Immunol 2021;12:686809. Epub 2021 Oct 28 doi: 10.3389/fimmu.2021.686809. PMID: 34777331Free PMC Article
Adams SA, Nasrallah HA
Schizophr Res 2018 May;195:3-12. Epub 2017 Jul 27 doi: 10.1016/j.schres.2017.07.018. PMID: 28755877
Alvarez PA, Pahissa J
Curr Drug Saf 2010 Jan;5(1):97-104. doi: 10.2174/157488610789869265. PMID: 20210726
Stöllberger C, Huber JO, Finsterer J
Int Clin Psychopharmacol 2005 Sep;20(5):243-51. doi: 10.1097/01.yic.0000166405.49473.70. PMID: 16096514
Zareba W, Lin DA
Psychiatr Q 2003 Fall;74(3):291-306. doi: 10.1023/a:1024122706337. PMID: 12918603

Diagnosis

Aslostovar L, Boyd AL, Benoit YD, Di Lu J, Garcia Rodriguez JL, Nakanishi M, Porras DP, Reid JC, Mitchell RR, Leber B, Xenocostas A, Foley R, Bhatia M
Cell Rep Med 2021 Feb 16;2(2):100202. doi: 10.1016/j.xcrm.2021.100202. PMID: 33665638Free PMC Article
Tegowski M, Fan C, Baldwin AS
Sci Rep 2019 Dec 10;9(1):18695. doi: 10.1038/s41598-019-55145-3. PMID: 31822725Free PMC Article
Singh V, Jaiswal PK, Ghosh I, Koul HK, Yu X, De Benedetti A
Cancer Lett 2019 Jul 1;453:131-141. Epub 2019 Mar 27 doi: 10.1016/j.canlet.2019.03.041. PMID: 30928383
Bola J, Kao D, Soydan H
Cochrane Database Syst Rev 2011 Jun 15;2011(6):CD006374. doi: 10.1002/14651858.CD006374.pub2. PMID: 21678355Free PMC Article
Menkes DB, Knight JC
Aust N Z J Psychiatry 2002 Aug;36(4):492-8. doi: 10.1046/j.1440-1614.2002.01045.x. PMID: 12169148

Therapy

Ren X, Chen X, Zhang X, Jiang S, Zhang T, Li G, Lu Z, Zhang D, Wang S, Qin C
Front Immunol 2021;12:686809. Epub 2021 Oct 28 doi: 10.3389/fimmu.2021.686809. PMID: 34777331Free PMC Article
Amaral L, Viveiros M, Molnar J, Kristiansen JE
Recent Pat Antiinfect Drug Discov 2011 May;6(2):84-7. doi: 10.2174/157489111796064542. PMID: 21548876
Stöllberger C, Huber JO, Finsterer J
Int Clin Psychopharmacol 2005 Sep;20(5):243-51. doi: 10.1097/01.yic.0000166405.49473.70. PMID: 16096514
Zareba W, Lin DA
Psychiatr Q 2003 Fall;74(3):291-306. doi: 10.1023/a:1024122706337. PMID: 12918603
DeVane CL, Nemeroff CB
Clin Pharmacokinet 2001;40(7):509-22. doi: 10.2165/00003088-200140070-00003. PMID: 11510628

Prognosis

Luo H, Chen J, Jiang Q, Yu Y, Yang M, Luo Y, Wang X
Clin Epigenetics 2023 Jun 12;15(1):100. doi: 10.1186/s13148-023-01515-8. PMID: 37309005Free PMC Article
Malard F, Jacquet E, Nhiri N, Sizun C, Chabrier A, Messaoudi S, Dejeu J, Betzi S, Zhang X, Thureau A, Lescop E
ChemMedChem 2022 Jan 5;17(1):e202100528. Epub 2021 Oct 6 doi: 10.1002/cmdc.202100528. PMID: 34472703
Ren X, Chen X, Zhang X, Jiang S, Zhang T, Li G, Lu Z, Zhang D, Wang S, Qin C
Front Immunol 2021;12:686809. Epub 2021 Oct 28 doi: 10.3389/fimmu.2021.686809. PMID: 34777331Free PMC Article
Amaral L, Viveiros M, Molnar J, Kristiansen JE
Recent Pat Antiinfect Drug Discov 2011 May;6(2):84-7. doi: 10.2174/157489111796064542. PMID: 21548876
Alvarez PA, Pahissa J
Curr Drug Saf 2010 Jan;5(1):97-104. doi: 10.2174/157488610789869265. PMID: 20210726

Clinical prediction guides

Ren X, Chen X, Zhang X, Jiang S, Zhang T, Li G, Lu Z, Zhang D, Wang S, Qin C
Front Immunol 2021;12:686809. Epub 2021 Oct 28 doi: 10.3389/fimmu.2021.686809. PMID: 34777331Free PMC Article
Alvarez PA, Pahissa J
Curr Drug Saf 2010 Jan;5(1):97-104. doi: 10.2174/157488610789869265. PMID: 20210726
Strachan EM, Kelly CA, Bateman DN
Eur J Clin Pharmacol 2004 Oct;60(8):541-5. Epub 2004 Sep 15 doi: 10.1007/s00228-004-0811-7. PMID: 15372128
DeVane CL, Nemeroff CB
Clin Pharmacokinet 2001;40(7):509-22. doi: 10.2165/00003088-200140070-00003. PMID: 11510628
Smith PJ, Talbert RL
Clin Pharm 1986 May;5(5):373-84. PMID: 2872991

Recent systematic reviews

Dold M, Samara MT, Li C, Tardy M, Leucht S
Cochrane Database Syst Rev 2015 Jan 16;1(1):CD009831. doi: 10.1002/14651858.CD009831.pub2. PMID: 25592299Free PMC Article
Bola J, Kao D, Soydan H
Cochrane Database Syst Rev 2011 Jun 15;2011(6):CD006374. doi: 10.1002/14651858.CD006374.pub2. PMID: 21678355Free PMC Article

Therapeutic recommendations

From Medical Genetics Summaries

This section contains excerpted 1 information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.

2016 Statement from the US Food and Drug Administration (FDA): Reduced cytochrome P450 2D6 isozyme activity drugs that 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 thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as Torsades de pointes type arrhythmias. Such an increased risk may result also from the additive effect of coadministering thioridazine with other agents that prolong the QTc interval. Therefore, thioridazine 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.

Please review the complete therapeutic recommendations that are located here: ( 1 ) .

1 The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labeled all formulations containing the generic drug.

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