A. Risperidone induces QT prolongation. ECG at the admission was normal and the corrected QT value (QTc; according to the Bazett formula) was not prolonged under the treatment of aripiprazol (20 mg/day), haloperidol (3 mg/day) and escitalopram (20 mg/day). Subsequently, the QTc value was monitored regularly. At day 4, 9 and 15 risperidone (2 x 1 mg/day) was introduced and thereafter rapidly stopped at day 4, 10 or 15, respectively, as indicated on the graph. Other antipsychotics/antidepressant were discontinued, as indicated on the graph. QTc prolongation was observed each time when risperidone was introduced, even after a single 1 mg dose, and it returned to the normal range immediately after the risperidone treatment was stopped. B. Comparative analysis of the impact of risperidone and clozapine on QT length. QTc values have been measured during the treatment with progressively increasing doses of clozapine (12,5 – 275 mg; n=14), risperidone (1 – 2 mg; n=3) or in the absence of these drugs (control; n=8). Risperidone but not clozapine caused statistically significant QTc prolongation in this patient, as assessed by Mann–Whitney U test. NS – statistically not significant. C. Plasma concentration of aripiprazol, clozapine and risperidone in relation to KCNH2 IC
50. Drug plasma concentration has been determined at the steady state, for aripiprazol and clozapine, or the second day after its introduction, for risperidone (2 x 1 mg/day), at the time of the predicted peak of the plasma drug level. On the graph, the drug concentrations have been expressed as a fold of their respective KCNH2 IC50values (263 nM for aripiprazol, 320 nM for clozapine, and 148 nM for risperidone), previously determined for these drugs. At the indicated concentrations, risperidone, but not aripiprazol or clozapine, significantly prolonged QT length.