Drugs such as amiodarone and racemic sotalol prolong the QT interval, but their torsadogenic potential is nowhere near as high as one might anticipate. Notwithstanding, QT interval is the best surrogate marker we currently have for TdP that, by definition, is associated with and follows concurrent prolongation of the QT interval. The level of risk varies with each neuroleptic, with thioridazine being highly torsadogenic. Although ziprasidone has been shown to block

the HERG channel in vitro and prolong the QTc interval in vivo in man, there have been no reported cases of TdP associated with Inhibitors,research,lifescience,medical its clinical use to date. A fuller picture will only emerge following its wider use. Other ancillary pharmacological properties Inhibitors,research,lifescience,medical of these drugs, particularly autonomic effects, no doubt, modulate their torsadogenic risk. While (+)-(S)-sotalol is highly torsadogenic, racemic sotalol is much less so because of the β-blocking activity of (-)-(R)-sotalol in the racemic drug.28,29 Sertindole

too selleck markedly prolongs the QT interval, but its powerful α-adrenoceptor (and possibly calcium channel)-blocking activity seems to offer Inhibitors,research,lifescience,medical a relative protection against the development of TdP. In one study of 1444 patients receiving a mean (SD) daily dose of 13.4 (5.6) mg sertindole, there were 15 reports of QTc interval prolongation with no cases of TdP.30 The risk is further modified by a number of other factors such as bradycardia, diminished basal repolarization reserve (as in congenital QT interval prolongation syndromes), cardiac disease, or electrolyte imbalance. In one study of 313 schizophrenic men, admitted on an emergency Inhibitors,research,lifescience,medical basis during a 24-month period, serum potassium concentration in the severely agitated group was lower than that in the mildly affected group. There was a significant, inverse correlation Inhibitors,research,lifescience,medical between serum potassium concentration and the level of symptoms of acute agitation. Improvement in serum level following sedation correlated with baseline acute

agitation.31 An association is documented between hypokalemia and acute psychotic decompensation in a patient with chronic schizophrenia.32 Some recent clinical studies also indicate that hypokalemia is a characteristic feature in acute psychotic patients at the time of emergency of admission. Since hypokalemia is one of the major causes of prolonged QT interval and TdP, it was not surprising to find that in 67 drug-free acute psychotic patients, the mean QTc interval was prolonged. The mean QTc interval of psychiatric emergency patients was longer than that of psychiatric outpatients. As psychiatric emergency patients often receive parenteral antipsychotics, it is evident why the QT-prolonging activity of a new neuroleptic agent should be thoroughly characterized.