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QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

Michela Sala1*, Alessandro Vicentini2, Paolo Brambilla4, Cristina Montomoli3, Jigar RS Jogia6, Eduardo Caverzasi1, Alberto Bonzano1, Marco Piccinelli5, Francesco Barale1 and Gaetano M De Ferrari2

Author Affiliations

1 Department of Health Sciences-Section of Psychiatry, IRCCS Policlinico S. Matteo, University of Pavia, School of Medicine, Pavia, Italy

2 Department of Cardiology, IRCCS Policlinico S. Matteo, University of Pavia, School of Medicine, Pavia, Italy

3 Department of Health Sciences, University of Pavia, Pavia, Italy

4 Department of Pathology and Experimental and Clinical Medicine, Section of Psychiatry, University of Udine School of Medicine, Udine, Italy

5 Psychiatry Unit, Azienda Ospedaliera Universitaria Ospedale di Circolo e Fondazione Macchi di Varese, Presidio Ospedaliero del Verbano – Italy

6 Section of Neurobiology of Psychosis, Institute of Psychiatry, London, UK

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Annals of General Psychiatry 2005, 4:1  doi:10.1186/1744-859X-4-1

Published: 25 January 2005



Several 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.


We 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.


Mean 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).


No 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.

antipsychotic; antidepressant; proarrhythmia; QTc interval