TITLE:
Antipsychotic Medication and Risk of QTc Prolongation: Focus on Multiple Medication and Role of Cytochrome P450 Isoforms
AUTHORS:
Takashi Ikeno, Kiyotaka Kugiyama, Hiroto Ito
KEYWORDS:
Antipsychotics, CYP, Drug Interaction, QTc Prolongation, Schizophrenia
JOURNAL NAME:
Open Journal of Psychiatry,
Vol.4 No.4,
October
22,
2014
ABSTRACT: Objective: To identify the effects of antipsychotics on QTc prolongation
in light of age, gender, antipsychotic combination pattern, antipsychotic doses
and cytochrome P450 (CYP) mediation, using large database describing the
antipsychotic treatment of patients with schizophrenia in Japan. Methods: Using
database of 4176 patients with schizophrenia discharged between April 2004 and
March 2005 and receiving outpatient treatment from 526 psychiatric hospitals in
Japan. Of the patients, 1437 were included for the analysis. These patients
were classified into three groups according
to the antipsychotic CPZ-equivalent doses that they received (low, 1 - 299 mg;
middle, 300 - 999 mg; and high, ≥1000 mg). QTc intervals ≥ 440 msec were considered prolonged. We reviewed all
the package inserts of the antipsychotics used from the website of
Pharmaceuticals and Medical Devices Agency. Results: The mean QTc interval of the total
patient group was 410.4 ± 23.3 msec. The females had significantly
higher QTc values than the males (414.5 ± 24.0 vs. 406.8 ± 22.2 msec, respectively; p 0.05). Logistic regression analysis revealed that female gender (odds
ratio [OR] = 1.83; 95% CI: 1.28 - 2.56), CYP3A4-metabolized drugs (OR 1.56; 95%
CI: 1.05 - 2.30) were associated with an increased risk of QTc prolongation.
Conclusion: The co-prescription of CYP3A4-mediated antipsychotic drugs should
be carefully considered in females due to potential risk of QTc prolongation.
Further studies of the cardiovascular safety of antipsychotics are warranted in
patients receiving multiple medications.