158 - Other risk factors

Other risk factors

164 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 1 Aripiprazole remains in the low-effect group having previously been firmly placed in ‘no effect’. Data are rather contradictory, with most studies showing a decrease in QTc associated with aripiprazole use,51 even in children and adolescents.72 However, later data60,61,63,65,73 cast doubt on assumptions of cardiac safety. Nonetheless, a 2020 paper analysing reports of events in >400,000 in-­patients over 20 years found aripiprazole had the lowest rate of cardiac events (0.06%) of all antipsychotics.74 Lurasidone remains in the ‘no-effect’ group,51 although one study mentioned in the US labelling75 reports a QT lengthening of 7.5ms in people receiving 120mg (111mg) a day. Those receiving 600mg (555mg) daily showed a lower change (+4.6ms). These findings are in some contrast with those from studies in patients which uniformly suggest no or minimal effect.76–78 This disparity is probably explained by the use of different correction factors and by random change, as often seen in placebo-­treated patients78 and as suggested by the apparent lack of dose-­related effect. One case of QTc >500ms has been reported with lurasidone in which lurasidone was judged the ‘probable’ cause.79 Brexpiprazole remains in the ‘no-effect’ group although one study of 16 patients found an increase in QTc (Hodges’ formula) of 10.1ms and an important increase in dispersion transmural repolarisation time.12 All other data suggest no effect. Other risk factors A number of physiological, pathological and genetic80 factors are associated with an increased risk of QT changes and of arrhythmia (Table 1.36) and many non-­psychotropic drugs are linked to QT prolongation (Table 1.37).25 These additional risk factors seem almost always to be present in cases of antipsychotic-­induced TdP.81 Table 1.36  Physiological risk factors for QTc prolongation and arrhythmia. Cardiac Long QT syndrome Bradycardia Ischaemic heart disease Myocarditis Myocardial infarction Left ventricular hypertrophy Metabolic Hypokalaemia Hypomagnesaemia Hypocalcaemia Others Extreme physical exertion Stress or shock Anorexia nervosa Extremes of age – children and elderly may be more susceptible to QT changes Female gender Note: Hypokalaemia-­related QTc prolongation is more commonly observed in acute psychotic admissions.82 There are a number of physical and genetic factors (related to cardiac potassium channels or CYP enzyme function),80 which may not be discovered on routine examination but which probably predispose patients to arrhythmia.83,84