U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

Nagel D, Spranger S, Vincendeau M, Grau M, Raffegerst S, Kloo B, Hlahla D, Neuenschwander M, Peter von Kries J, Hadian K, Dörken B, Lenz P, Lenz G, Schendel DJ, Krappmann D
Cancer Cell 2012 Dec 11;22(6):825-37. doi: 10.1016/j.ccr.2012.11.002. PMID: 23238017
Ahmed A
J Am Geriatr Soc 1968 Aug;16(8):945-7. doi: 10.1111/j.1532-5415.1968.tb02690.x. PMID: 5691150
Bártová D, Bouchal M
Act Nerv Super (Praha) 1965 Aug;7(3):244-5. PMID: 5882091

Curated

DailyMed Drug Label, thioridazine, 2019

DailyMed Drug Label, THIORIDAZINE HYDROCHLORIDE, 2016

Recent clinical studies

Etiology

Prescrire Int 2002 Oct;11(61):146-50. PMID: 12378746
Reilly JG, Ayis SA, Ferrier IN, Jones SJ, Thomas SH
Br J Psychiatry 2002 Jun;180:515-22. doi: 10.1192/bjp.180.6.515. PMID: 12042230
Ray WA, Meredith S, Thapa PB, Meador KG, Hall K, Murray KT
Arch Gen Psychiatry 2001 Dec;58(12):1161-7. doi: 10.1001/archpsyc.58.12.1161. PMID: 11735845
Dubin WR, Waxman HM, Weiss KJ, Ramchandani D, Tavani-Petrone C
J Clin Psychiatry 1985 Nov;46(11):475-8. PMID: 2865251
Georgotas A, Gerbino L, Jordan B, McCarthy M, Gershon S, Kleinberg D, Lautin A, Stanley M, Rotrosen J
Psychopharmacology (Berl) 1981;73(3):292-4. doi: 10.1007/BF00422420. PMID: 6113618

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
Hamid R, Rotshteyn Y, Rabadi L, Parikh R, Bullock P
Toxicol In Vitro 2004 Oct;18(5):703-10. doi: 10.1016/j.tiv.2004.03.012. PMID: 15251189
Reisberg B, Borenstein J, Salob SP, Ferris SH, Franssen E, Georgotas A
J Clin Psychiatry 1987 May;48 Suppl:9-15. PMID: 3553166
Dubin WR, Waxman HM, Weiss KJ, Ramchandani D, Tavani-Petrone C
J Clin Psychiatry 1985 Nov;46(11):475-8. PMID: 2865251
Georgotas A, Gerbino L, Jordan B, McCarthy M, Gershon S, Kleinberg D, Lautin A, Stanley M, Rotrosen J
Psychopharmacology (Berl) 1981;73(3):292-4. doi: 10.1007/BF00422420. PMID: 6113618

Therapy

Shen S, Faouzi S, Souquere S, Roy S, Routier E, Libenciuc C, André F, Pierron G, Scoazec JY, Robert C
Cell Rep 2020 Nov 24;33(8):108421. doi: 10.1016/j.celrep.2020.108421. PMID: 33238129
DeVane CL, Nemeroff CB
Clin Pharmacokinet 2001;40(7):509-22. doi: 10.2165/00003088-200140070-00003. PMID: 11510628
Alexander B
Drug Intell Clin Pharm 1988 Apr;22(4):324-6. doi: 10.1177/106002808802200412. PMID: 2897277
Georgotas A, Gerbino L, Jordan B, McCarthy M, Gershon S, Kleinberg D, Lautin A, Stanley M, Rotrosen J
Psychopharmacology (Berl) 1981;73(3):292-4. doi: 10.1007/BF00422420. PMID: 6113618
Simeon J, Utech C, Simeon S, Itil TM
Dis Nerv Syst 1974 Jul;35(7 Pt. 2):37-47. PMID: 17894102

Prognosis

Ray WA, Meredith S, Thapa PB, Meador KG, Hall K, Murray KT
Arch Gen Psychiatry 2001 Dec;58(12):1161-7. doi: 10.1001/archpsyc.58.12.1161. PMID: 11735845
Gedye A
Ment Retard 1998 Jun;36(3):182-6. doi: 10.1352/0047-6765(1998)036<0182:NDDIFA>2.0.CO;2. PMID: 9638038
Devanand DP
Int Psychogeriatr 1996;8 Suppl 3:355-61; discussion 381-2. doi: 10.1017/s1041610297003621. PMID: 9154588
Ayers T, Liberman RP, Wallace CJ
J Clin Psychopharmacol 1984 Apr;4(2):89-93. doi: 10.1097/00004714-198404020-00005. PMID: 6707245
Donlon PT, Tupin JP
Arch Gen Psychiatry 1977 Aug;34(8):955-7. doi: 10.1001/archpsyc.1977.01770200093012. PMID: 889420

Clinical prediction guides

Janowsky DS, Barnhill LJ, Shetty M, Davis JM
J Clin Psychopharmacol 2005 Feb;25(1):19-25. doi: 10.1097/01.jcp.0000150218.51433.7b. PMID: 15643096
DeVane CL, Nemeroff CB
Clin Pharmacokinet 2001;40(7):509-22. doi: 10.2165/00003088-200140070-00003. PMID: 11510628
Ayers T, Liberman RP, Wallace CJ
J Clin Psychopharmacol 1984 Apr;4(2):89-93. doi: 10.1097/00004714-198404020-00005. PMID: 6707245
Schneider SJ
Psychol Med 1982 Aug;12(3):607-13. doi: 10.1017/s0033291700055719. PMID: 7134318
Carroll BJ, Curtis GC, Kokmen E
Am J Psychiatry 1977 Jul;134(7):785-9. doi: 10.1176/ajp.134.7.785. PMID: 17308

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.

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...