531832 research-article2014
ANP0010.1177/0004867414531832ANZJP CorrespondenceANZJP Correspondence
Letter Australian & New Zealand Journal of Psychiatry 1–1
Letter
© The Royal Australian and New Zealand College of Psychiatrists 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav anp.sagepub.com
QTc prolongation with asenapine Felix Kotasek1, Prashant Tibrewal2 and Rohan Dhillon2 1University
of Adelaide, Adelaide, Australia Queen Elizabeth Hospital, Woodville, South Adelaide, Australia
2The
Corresponding author: Prashant Tibrewal, Queen Elizabeth Hospital, c/- Cramond Clinic, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia. Email: [email protected] DOI: 10.1177/0004867414531832
To the Editor Prolongation of QTc is a relatively common adverse effect of antipsychotic medication. QTc prolongation has been associated with development of potentially fatal cardiac arrhythmias, most notably torsades de pointes. The primary mechanism whereby antipsychotics induce QTc prolongation is through their blockage of the hERG rapid-delayed rectifier potassium channels in cardiomyocytes (Menkes and Knight, 2002). Asenapine is a recently introduced atypical antipsychotic that, in Australia, is indicated in the treatment of schizophrenia and bipolar I disorder. Presently, there is limited information available regarding asenapine’s effect on QTc, aside from manufacturer information. In a study of asenapine’s effect on QTc, Chapel et al. (2009) concluded that asenapine did
not have a clinically relevant effect on the QT interval. We present a case of asenapine-induced QTc prolongation. Mr C is a 54-year-old man with a long history of clozapine-resistant schizophrenia who presented to hospital in late 2013 following a psychotic relapse. Over the last decade, antipsychotics including aripiprazole, amisupride, ziprasidone and paliperidone have been used to augment his clozapine. At the time of his recent admission, a routine ECG was conducted revealing a prolonged QTc of 496 ms on the combination of clozapine and quetiapine. Quetiapine, a drug associated with moderate increases in QTc, was immediately ceased and his QTc reduced to 470 ms. After receiving advice from cardiology, asenapine was selected to replace quetiapine for its purportedly low effect on QTc. However, within 24 hours of commencing asenapine, an ECG revealed Mr C’s QT had risen 30 ms to 500 ms. Asenapine was immediately ceased, and his QTc fell once again, and remained within acceptable limits for the remainder of his admission. The QTc prolongation seen after Mr C was commenced on asenapine is consistent with a Naranjo score of 7, indicating probable causation (Naranjo et al., 1981). Subsequently, olanzapine was used to augment his clozapine with no marked effect on QTc. Independently of each other, clozapine and asenapine are two drugs
that have ostensibly minor effects on QTc. However, when used in conjunction with one another in this case, these drugs led to significant QTc prolongation. Whilst no firm conclusions can be drawn from a single case, it highlights the need for further research into asenapine’s effects on QTc, especially in the context of combination therapy with other antipsychotics. Additionally, this case highlights the importance of ECG monitoring of patients on multiple antipsychotic therapy, given its common clinical practice in treatment resistant schizophrenia. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Chapel S, Hutmacher MM, Haig G, et al. (2009) Exposure-response analysis in patients with schizophrenia to assess the effect of asenapine on QTc prolongation. The Journal of Clinical Pharmacology 30: 1297–1308. Menkes DB and Knight JC (2002) Cardiotoxicity and prescription of thioridazine in New Zealand. Australian and New Zealand Journal of Psychiatry 36: 492–498. Naranjo CA, Busto U, Sellers EM, et al. (1981) A method for estimating the probability of adverse drug reactions. Clinical Pharmacology and Therapeutics 30: 239–245.
Australian & New Zealand Journal of Psychiatry Downloaded from anp.sagepub.com at UNIV OF GEORGIA LIBRARIES on May 26, 2015
ANP531832.indd 1
10/04/2014 10:51:11 AM
ANP0010.1177/0004867414531832ANZJP CorrespondenceANZJP Correspondence
Letter Australian & New Zealand Journal of Psychiatry 1–1
Letter
© The Royal Australian and New Zealand College of Psychiatrists 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav anp.sagepub.com
QTc prolongation with asenapine Felix Kotasek1, Prashant Tibrewal2 and Rohan Dhillon2 1University
of Adelaide, Adelaide, Australia Queen Elizabeth Hospital, Woodville, South Adelaide, Australia
2The
Corresponding author: Prashant Tibrewal, Queen Elizabeth Hospital, c/- Cramond Clinic, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia. Email: [email protected] DOI: 10.1177/0004867414531832
To the Editor Prolongation of QTc is a relatively common adverse effect of antipsychotic medication. QTc prolongation has been associated with development of potentially fatal cardiac arrhythmias, most notably torsades de pointes. The primary mechanism whereby antipsychotics induce QTc prolongation is through their blockage of the hERG rapid-delayed rectifier potassium channels in cardiomyocytes (Menkes and Knight, 2002). Asenapine is a recently introduced atypical antipsychotic that, in Australia, is indicated in the treatment of schizophrenia and bipolar I disorder. Presently, there is limited information available regarding asenapine’s effect on QTc, aside from manufacturer information. In a study of asenapine’s effect on QTc, Chapel et al. (2009) concluded that asenapine did
not have a clinically relevant effect on the QT interval. We present a case of asenapine-induced QTc prolongation. Mr C is a 54-year-old man with a long history of clozapine-resistant schizophrenia who presented to hospital in late 2013 following a psychotic relapse. Over the last decade, antipsychotics including aripiprazole, amisupride, ziprasidone and paliperidone have been used to augment his clozapine. At the time of his recent admission, a routine ECG was conducted revealing a prolonged QTc of 496 ms on the combination of clozapine and quetiapine. Quetiapine, a drug associated with moderate increases in QTc, was immediately ceased and his QTc reduced to 470 ms. After receiving advice from cardiology, asenapine was selected to replace quetiapine for its purportedly low effect on QTc. However, within 24 hours of commencing asenapine, an ECG revealed Mr C’s QT had risen 30 ms to 500 ms. Asenapine was immediately ceased, and his QTc fell once again, and remained within acceptable limits for the remainder of his admission. The QTc prolongation seen after Mr C was commenced on asenapine is consistent with a Naranjo score of 7, indicating probable causation (Naranjo et al., 1981). Subsequently, olanzapine was used to augment his clozapine with no marked effect on QTc. Independently of each other, clozapine and asenapine are two drugs
that have ostensibly minor effects on QTc. However, when used in conjunction with one another in this case, these drugs led to significant QTc prolongation. Whilst no firm conclusions can be drawn from a single case, it highlights the need for further research into asenapine’s effects on QTc, especially in the context of combination therapy with other antipsychotics. Additionally, this case highlights the importance of ECG monitoring of patients on multiple antipsychotic therapy, given its common clinical practice in treatment resistant schizophrenia. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Chapel S, Hutmacher MM, Haig G, et al. (2009) Exposure-response analysis in patients with schizophrenia to assess the effect of asenapine on QTc prolongation. The Journal of Clinical Pharmacology 30: 1297–1308. Menkes DB and Knight JC (2002) Cardiotoxicity and prescription of thioridazine in New Zealand. Australian and New Zealand Journal of Psychiatry 36: 492–498. Naranjo CA, Busto U, Sellers EM, et al. (1981) A method for estimating the probability of adverse drug reactions. Clinical Pharmacology and Therapeutics 30: 239–245.
Australian & New Zealand Journal of Psychiatry Downloaded from anp.sagepub.com at UNIV OF GEORGIA LIBRARIES on May 26, 2015
ANP531832.indd 1
10/04/2014 10:51:11 AM
