QT Alterations in Psychopharmacology: Proven Candidates and Suspects

Alvarez, Paulino Antonio; Pahissa, Jaime
January 2010
Current Drug Safety;Jan2010, Vol. 5 Issue 1, p97
Academic Journal
Psychotropics are among the most common causes of drug induced acquired long QT syndrome. Blockage of Human ether-ago-go-related gene (HERG) potassium channel by psychoactive drugs appears to be related to this adverse effect. Antipsychotics such as haloperidol, thioridazine, sertindole, pimozide, risperidone, ziprasidone, quetiapine, olanzapine and antidepressants such as amitriptyline, imipramine, doxepin, trazadone, fluoxetine depress the delayed rectifier potassium current (Ikr) in a dose dependent manner in experimental models. The frequency of QTc prolongation (more than 456ms) in psychiatric patients is estimated to be 8%. Age over 65 years, tricyclic antidepressants (TCA), thioridazine, droperidol, olanzapine, and higher antipsychotic doses were predictors of significant QTc prolongation. In large epidemiological controlled studies a dose dependent increased risk of sudden death has been identified in current users of antipsychotics (conventional and atypical) and of TCA. Thioridazine and haloperidol shared a similar relative risk of SCD. Lower doses of risperidone had a higher relative risk than haloperidol for cardiac arrest and ventricular arrhythmia. No increased risk was identified in current users of selective serotonin reuptake inhibitors (SSRI). Cases of TdP have been reported with thioridazine, haloperidol, ziprazidone, olanzapine and TCA. Evidence of QTc prolongation with sertindole is significant and this drug has not been approved by the Food and Drugs Administration (FDA). A large trial is ongoing to evaluate the cardiac risk profile of ziprazidone and olanzapine. Selective serotonin reuptake inhibitors have been associated with QTc prolongation but no cases of TdP have been reported with the use of these agents. There are no reported cases of lithium induced TdP. Risk factors for drug induced LQT syndrome and TdP include: female gender, concomitant cardiovascular disease, substance abuse, drug interactions, bradychardia, electrolyte disorders, anorexia nervosa, and congenital Long QT syndrome. Careful selection of the psychotropic and identification of patient's risk factors for QTc prolongation is applicable in current clinical practice.


Related Articles

  • Other Drugs Acting on Nervous System Associated with QT-Interval Prolongation. Keller, Guillermo Alberto; Ponte, Marcelo L.; Di Girolamo, Guillermo // Current Drug Safety;Jan2010, Vol. 5 Issue 1, p105 

    Several drugs acting on the nervous system have been implicated in the prolongation of the QT interval. Leaving aside the antidepressant and antipsychotic drugs, some have shown to prolong the QT interval in vivo. These include opioids, particularly methadone, inhalational anesthetics, and some...

  • hERG channel function: beyond long QT. Babcock, Joseph J; Li, Min // Acta Pharmacologica Sinica;Mar2013, Vol. 34 Issue 3, p329 

    To date, research on the human ether-a-go-go related gene (hERG) has focused on this potassium channel's role in cardiac repolarization and Long QT Syndrome (LQTS). However, growing evidence implicates hERG in a diversity of physiologic and pathological processes. Here we discuss these other...

  • Mechanistic Basis for Type 2 Long QT Syndrome Caused by KCNH2 Mutations that Disrupt Conserved Arginine Residues in the Voltage Sensor. McBride, Christie; Smith, Ashley; Smith, Jennifer; Reloj, Allison; Velasco, Ellyn; Powell, Jonathan; Elayi, Claude; Bartos, Daniel; Burgess, Don; Delisle, Brian // Journal of Membrane Biology;May2013, Vol. 246 Issue 5, p355 

    KCNH2 encodes the Kv11.1 channel, which conducts the rapidly activating delayed rectifier K current ( I) in the heart. KCNH2 mutations cause type 2 long QT syndrome (LQT2), which increases the risk for life-threatening ventricular arrhythmias. LQT2 mutations are predicted to prolong the cardiac...

  • KCNE1 D85N polymorphism -- a sex-specific modifier in type 1 long QT syndrome? Lahtinen, Annukka M.; Marjamaa, Annukka; Swan, Heikki; Kontula, Kimmo // BMC Medical Genetics;2011, Vol. 12 Issue 1, p1 

    Background: Long QT syndrome (LQTS) is an inherited ion channel disorder manifesting with prolongation of the cardiac repolarization phase and severe ventricular arrhythmias. The common KCNE1 D85N potassium channel variant prolongs QT interval by inhibiting IKs (KCNQ1) and IKr (KCNH2) currents...

  • hERG potassium channels and cardiac arrhythmia. Sanguinetti, Michael C.; Tristani-Firouzi, Martin // Nature;3/23/2006, Vol. 440 Issue 7083, p463 

    hERG potassium channels are essential for normal electrical activity in the heart. Inherited mutations in the HERG gene cause long QT syndrome, a disorder that predisposes individuals to life-threatening arrhythmias. Arrhythmia can also be induced by a blockage of hERG channels by a surprisingly...

  • Genome-wide association study of antipsychotic-induced QTc interval prolongation. Åberg, K; Adkins, D E; Liu, Y; McClay, J L; Bukszár, J; Jia, P; Zhao, Z; Perkins, D; Stroup, T S; Lieberman, J A; Sullivan, P F; van den Oord, E J C G // Pharmacogenomics Journal;Apr2012, Vol. 12 Issue 2, p165 

    QT prolongation is associated with increased risk of cardiac arrhythmias. Identifying the genetic variants that mediate antipsychotic-induced prolongation may help to minimize this risk, which might prevent the removal of efficacious drugs from the market. We performed candidate gene analysis...

  • QTc Prolongation in Patients Acutely Admitted to Hospital for Psychosis and Treated with Second Generation Antipsychotics. Johnsen, Erik; Aanesen, Kristina; Sriskandarajah, Sanjeevan; Kroken, Rune A.; Løberg, Else-Marie; Jørgensen, Hugo A. // Schizophrenia Research & Treatment;2013, p1 

    QTc interval prolongation is a side effect of several antipsychotic drugs, with associated risks of torsade de pointes arrhythmias and sudden cardiac death. There is an ongoing debate of whether or not electrocardiogram (ECG) assessments should be mandatory in patients starting antipsychotic...

  • Causes and management of drug-induced long QT syndrome. Ayad, Ramy F.; Assar, Manish D.; Simpson, Leo; Garner, John B.; Schussler, Jeffrey M. // Baylor University Medical Center Proceedings;Jul2010, Vol. 23 Issue 3, p250 

    Long QT syndrome (LQTS) is characterized by inherited or acquired prolonged QT interval on the surface electrocardiogram. This can lead to torsade de pointes ventricular tachycardia (TdP VT) and ventricular fibrillation. In the acquired form of the disease, medications from several classes can...

  • Evolutionary analyses of KCNQ1 and HERG voltage-gated potassium channel sequences reveal location-specific susceptibility and augmented chemical severities of arrhythmogenic mutations. Jackson, Heather A.; Accili, Eric A. // BMC Evolutionary Biology;2008, Vol. 8, Special section p1 

    Background: Mutations in HERG and KCNQ1 potassium channels have been associated with Long QT syndrome and atrial fibrillation, and more recently with sudden infant death syndrome and sudden unexplained death. In other proteins, disease-associated amino acid mutations have been analyzed according...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics