Published online Dec 22, 2016. doi: 10.5498/wjp.v6.i4.442
Peer-review started: July 2, 2016
First decision: August 5, 2016
Revised: September 9, 2016
Accepted: October 5, 2016
Article in press: October 9, 2016
Published online: December 22, 2016
To investigate whether differential influence on the QTc interval exists among four second generation antipsychotics (SGAs) in psychosis.
Data were drawn from a pragmatic, randomized head-to-head trial of the SGAs risperidone, olanzapine, quetiapine, and ziprasidone in acute admissions patients with psychosis, and with follow-up visits at discharge or maximally 6-9 wk, 3, 6, 12 and 24 mo. Electrocardiograms were recorded on all visits. To mimic clinical shared decision-making, the patients were randomized not to a single drug, but to a sequence of the SGAs under investigation. The first drug in the sequence defined the randomization group, but the patient and/or clinician could choose an SGA later in the sequence if prior negative experiences with the first one(s) in the sequence had occurred. The study focuses on the time of, and actual use of the SGAs under investigation, that is until treatment discontinuation or change, in order to capture the direct medication effects on the QTc interval. Secondary intention-to-treat (ITT) analyses were also performed.
A total of 173 patients, with even distribution among the treatment groups, underwent ECG assessments. About 70% were males and 43% had never used antipsychotic drugs before the study. The mean antipsychotic doses in milligrams per day with standard deviations (SD) were 3.4 (1.2) for risperidone, 13.9 (4.6) for olanzapine, 325.9 (185.8) for quetiapine, and 97.2 (42.8) for ziprasidone treated groups. The time until discontinuation of the antipsychotic drug used did not differ in a statistically significant way among the groups (Log-Rank test: P = 0.171). The maximum QTc interval recorded during follow-up was 462 ms. Based on linear mixed effects analyses, the QTc interval change per day with standard error was -0.0030 (0.0280) for risperidone; -0.0099 (0.0108) for olanzapine; -0.0027 (0.0170) for quetiapine, and -0.0081 (0.0229) for ziprasidone. There were no statistically significant differences among the groups in this regard. LME analyses based on ITT groups (the randomization groups), revealed almost identical slopes with -0.0063 (0.0160) for risperidone, -0.0130 (0.0126) for olanzapine, -0.0034 (0.0168) for quetiapine, and -0.0045 (0.0225) for ziprasidone.
None of the SGAs under investigation led to statistically significant QTc prolongation. No statistically significant differences among the SGAs were found.
Core tip: Antipsychotic drugs have a bad reputation of prolonging the QTc interval, and thereby possibly leading to fatal incidents of Torsade de pointes arrhythmias and sudden cardiac death. Differential propensities for QTc prolongation among second generation antipsychotics (SGAs) have been claimed, but lack substantial support from pragmatic studies. None of the SGAs was statistically significantly prolonging the QTc interval in the present pragmatic study, and no statistically significant differences among the drug groups were found for this outcome. Even in a situation with a substantial proportion with QTc prolongation at admittance any of the SGAs under investigation seemed to be safe choices in the present study.