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Recently Medsafes Medicines Adverse Reactions Committee (MARC) published an assessment of QTc prolongation and antidepressants, and concluded that QT prolongation... is a risk of treatment with most of the antidepressants approved for use in NZ .1 A more detailed set of minutes from this meeting has been also published.2Good quality data to support these conclusions are available for citalopram and escitalopram. For the remaining drugs, data are of poor quality, or have to be inferred from unusual circumstances (e.g. associated with very high blood levels after overdose, which may also involve ingestion of other drugs). Ideally, statements on QTc prolongation would be based on data generated in a Thorough QT study, which is methodologically demanding.3 Alternatively, large simple trial designs can be used to evaluate cardiac safety of drugs.4 Inference of QTc prolongation from in vitro HERG binding data may be less than ideal, as some drugs which are potent HERG inhibitors have no clinical cardiac safety signals,5,6 or have negative Thorough QT data.6Realistically, the relationship between therapeutic use of most antidepressants and changes in QTc cannot be assessed at this time, and MARCs statement in Prescriber Update1 appears to be unnecessarily alarming. If unchallenged, we are concerned that this might unnecessarily influence doctors prescribing habits, or dissuade patients from valuable therapeutic options for depression or anxiety. Paul Glue Professor and Hazel Buckland Chair in Psychological Medicine Chris Gale Senior Lecturer in Psychological Medicine Dunedin School of Medicine, University of Otago, Dunedin

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

Paul Glue, Professor and Hazel Buckland Chair in Psychological Medicine, Chris Gale, Senior Lecturer in Psychological Medicine, Dunedin School of Medicine, University of Otago, Dunedin

Acknowledgements

Correspondence

Correspondence Email

Competing Interests

In the last 3 years, Professor Glue was on the Scientific Advisory Board of Demerx Pharmaceuticals, and attended scientific advisory boards for Janssen. Dr Gale has been on speakers bureaux for Lilly and Janssen, and has had travel costs supported by Lilly.

Anonymous. Do all antidepressants cause QT prolongation? Prescriber Update 2012;33:33-35.http://www.medsafe.govt.nz/profs/adverse/Minutes151.htm Accessed 4/2/13ICH E14: Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs - Questions and Answers. October 2012.http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm323656.htm Accessed 4/2/13Strom BL, Eng SM, Faich G et al. Comparative mortality associated with ziprasidone and olanzapine in real-world use among 18,154 patients with schizophrenia: The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC). Am J Psychiatry 2011;168:193-201.Redfern WS, Carlsson L, Davis AS et al. Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc Res 2003;58:32-45.Malhotra BK, Glue P, Sweeney K et al. Thorough QT study with recommended and supratherapeutic doses of tolterodine. Clin Pharmacol Ther 2007;81:377-85.

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Recently Medsafes Medicines Adverse Reactions Committee (MARC) published an assessment of QTc prolongation and antidepressants, and concluded that QT prolongation... is a risk of treatment with most of the antidepressants approved for use in NZ .1 A more detailed set of minutes from this meeting has been also published.2Good quality data to support these conclusions are available for citalopram and escitalopram. For the remaining drugs, data are of poor quality, or have to be inferred from unusual circumstances (e.g. associated with very high blood levels after overdose, which may also involve ingestion of other drugs). Ideally, statements on QTc prolongation would be based on data generated in a Thorough QT study, which is methodologically demanding.3 Alternatively, large simple trial designs can be used to evaluate cardiac safety of drugs.4 Inference of QTc prolongation from in vitro HERG binding data may be less than ideal, as some drugs which are potent HERG inhibitors have no clinical cardiac safety signals,5,6 or have negative Thorough QT data.6Realistically, the relationship between therapeutic use of most antidepressants and changes in QTc cannot be assessed at this time, and MARCs statement in Prescriber Update1 appears to be unnecessarily alarming. If unchallenged, we are concerned that this might unnecessarily influence doctors prescribing habits, or dissuade patients from valuable therapeutic options for depression or anxiety. Paul Glue Professor and Hazel Buckland Chair in Psychological Medicine Chris Gale Senior Lecturer in Psychological Medicine Dunedin School of Medicine, University of Otago, Dunedin

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

Paul Glue, Professor and Hazel Buckland Chair in Psychological Medicine, Chris Gale, Senior Lecturer in Psychological Medicine, Dunedin School of Medicine, University of Otago, Dunedin

Acknowledgements

Correspondence

Correspondence Email

Competing Interests

In the last 3 years, Professor Glue was on the Scientific Advisory Board of Demerx Pharmaceuticals, and attended scientific advisory boards for Janssen. Dr Gale has been on speakers bureaux for Lilly and Janssen, and has had travel costs supported by Lilly.

Anonymous. Do all antidepressants cause QT prolongation? Prescriber Update 2012;33:33-35.http://www.medsafe.govt.nz/profs/adverse/Minutes151.htm Accessed 4/2/13ICH E14: Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs - Questions and Answers. October 2012.http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm323656.htm Accessed 4/2/13Strom BL, Eng SM, Faich G et al. Comparative mortality associated with ziprasidone and olanzapine in real-world use among 18,154 patients with schizophrenia: The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC). Am J Psychiatry 2011;168:193-201.Redfern WS, Carlsson L, Davis AS et al. Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc Res 2003;58:32-45.Malhotra BK, Glue P, Sweeney K et al. Thorough QT study with recommended and supratherapeutic doses of tolterodine. Clin Pharmacol Ther 2007;81:377-85.

For the PDF of this article,
contact nzmj@nzma.org.nz

View Article PDF

Recently Medsafes Medicines Adverse Reactions Committee (MARC) published an assessment of QTc prolongation and antidepressants, and concluded that QT prolongation... is a risk of treatment with most of the antidepressants approved for use in NZ .1 A more detailed set of minutes from this meeting has been also published.2Good quality data to support these conclusions are available for citalopram and escitalopram. For the remaining drugs, data are of poor quality, or have to be inferred from unusual circumstances (e.g. associated with very high blood levels after overdose, which may also involve ingestion of other drugs). Ideally, statements on QTc prolongation would be based on data generated in a Thorough QT study, which is methodologically demanding.3 Alternatively, large simple trial designs can be used to evaluate cardiac safety of drugs.4 Inference of QTc prolongation from in vitro HERG binding data may be less than ideal, as some drugs which are potent HERG inhibitors have no clinical cardiac safety signals,5,6 or have negative Thorough QT data.6Realistically, the relationship between therapeutic use of most antidepressants and changes in QTc cannot be assessed at this time, and MARCs statement in Prescriber Update1 appears to be unnecessarily alarming. If unchallenged, we are concerned that this might unnecessarily influence doctors prescribing habits, or dissuade patients from valuable therapeutic options for depression or anxiety. Paul Glue Professor and Hazel Buckland Chair in Psychological Medicine Chris Gale Senior Lecturer in Psychological Medicine Dunedin School of Medicine, University of Otago, Dunedin

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

Paul Glue, Professor and Hazel Buckland Chair in Psychological Medicine, Chris Gale, Senior Lecturer in Psychological Medicine, Dunedin School of Medicine, University of Otago, Dunedin

Acknowledgements

Correspondence

Correspondence Email

Competing Interests

In the last 3 years, Professor Glue was on the Scientific Advisory Board of Demerx Pharmaceuticals, and attended scientific advisory boards for Janssen. Dr Gale has been on speakers bureaux for Lilly and Janssen, and has had travel costs supported by Lilly.

Anonymous. Do all antidepressants cause QT prolongation? Prescriber Update 2012;33:33-35.http://www.medsafe.govt.nz/profs/adverse/Minutes151.htm Accessed 4/2/13ICH E14: Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs - Questions and Answers. October 2012.http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm323656.htm Accessed 4/2/13Strom BL, Eng SM, Faich G et al. Comparative mortality associated with ziprasidone and olanzapine in real-world use among 18,154 patients with schizophrenia: The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC). Am J Psychiatry 2011;168:193-201.Redfern WS, Carlsson L, Davis AS et al. Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc Res 2003;58:32-45.Malhotra BK, Glue P, Sweeney K et al. Thorough QT study with recommended and supratherapeutic doses of tolterodine. Clin Pharmacol Ther 2007;81:377-85.

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