Abstract
BackgroundSeveral antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc) exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment.MethodWe examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine) and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine) with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine) or lithium. An Electrocardiogram (ECG) was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic.Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test.ResultsMean QTc intervals significantly increased in Group 2 (24 ± 21 ms) however this was not the case in Group 1 (-1 ± 30 ms) (Repeated measures ANOVA p < 0,01). Furthermore we found a significant difference in the number of patients who exceeded the threshold of borderline QTc interval value (450 ms) between the two groups, with seven patients in Group 2 (38%) compared to one patient in Group 1 (7%) (Fisher Exact Text, p < 0,05).ConclusionsNo significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a combined treatment of antipsychotic and antidepressant agents.
Highlights
Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner
Careful monitoring of the QT interval is suggested in patients taking a combined treatment of antipsychotic and antidepressant agents
According to a document presented by the Committee for Proprietary Medicinal Products (CPMP) in 1997, normal subjects can be divided into three groups based on QTc interval length
Summary
Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. The QTc interval is a heart rate corrected value that measures the time between the onset and the end of electrical ventricular activity. Prolongation of this interval is considered a marker of the arrhythmogenic potential of a drug linked to an increased risk of torsade de pointes ventricular tachycardia [1]. Whereas for females QTc values less than ms are normal, between and 470 ms are borderline and over 470 ms are prolonged [2] This sex difference appears to be androgen driven and not determined by female hormones: at birth, QTc interval measurements are the same for male and female infants. The male QTc interval shortens and remains shorter than its female counterpart by about 20 ms until ages 50 to 55 years, coincident with a decline in testosterone levels baseline QTc interval duration doesn't show significant fluctuations during the menstrual cycle and Hormone Replacement Therapy in postmenopausal age doesn't affect QTc interval [3]
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