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Risk of QT Prolongation with Mood Stabilizers and Other Medications Scott R. Beach, M. D. Attending Psychiatrist, Massachusetts General Hospital Assistant Professor of Psychiatry, Harvard Medical School

Lithium and QT Prolongation Relatively safe No significant association with QT prolongation Supratherapeutic doses > 1. 2 mmol/L Prolong the QT interval - Reilly JG, Ayis SA, Ferrier IN, Jones SJ, Thomas SH. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet (London, England). 2000; 355: 1048 -1052. - Hsu, C. H. , Liu, P. Y. , Chen, J. H. , Yeh, T. L. , Tsai, H. Y. , & Lin, L. J. (2005). Electrocardiographic abnormalities as predictors for over-range lithium levels. Cardiology, 103(2), 101 -106. - Mamiya, K. , Sadanaga, T. , Sekita, A. , Nabeyama, Y. , Yao, H. , & Yukawa, E. (2005). Lithium concentration correlates with QTc in patients with psychosis. Journal of electrocardiology, 38(2), 148 -151.

Therapeutic blood levels Determinants for QT prolongation • • • Sex Low K+ concentration High lithium concentrations No QT prolongation Lithium Supratherapeutic doses + Other risk factors Increased QT interval - Reilly JG, Ayis SA, Ferrier IN, Jones SJ, Thomas SH. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet (London, England). 2000; 355: 1048 -1052. - Hsu, C. H. , Liu, P. Y. , Chen, J. H. , Yeh, T. L. , Tsai, H. Y. , & Lin, L. J. (2005). Electrocardiographic abnormalities as predictors for over-range lithium levels. Cardiology, 103(2), 101 -106. - Mamiya, K. , Sadanaga, T. , Sekita, A. , Nabeyama, Y. , Yao, H. , & Yukawa, E. (2005). Lithium concentration correlates with QTc in patients with psychosis. Journal of electrocardiology, 38(2), 148 -151.

Antiepileptic Drugs and QT Prolongation Carbamazepine Oxcarbazepine Valproate Lamotrigine Not significantly associated with QT prolongation Lower QT dispersion Slight decrease in QT intervals - Beach, S. R. , Celano, C. M. , Noseworthy, P. A. , Januzzi, J. L. , & Huffman, J. C. (2013). QTc prolongation, torsades de pointes, and psychotropic medications. Psychosomatics, 54(1), 1 -13. - Kurt, E. , Emul, M. , Ozbulut, O. , Guler, O. , Erdur, F. , Saglam, H. , & Gecici, O. (2009). Is valproate promising in cardiac fatal arrhythmias? Comparison of P-and Q-wave dispersion in bipolar. Journal of Psychopharmacology, 23(3), 328 -333. - Kwon, S. , Lee, S. , Hyun, M. , Choe, B. H. , Kim, Y. , Park, W. , & Cho, Y. (2004). The potential for QT prolongation by antiepileptic drugs in children. Pediatric neurology, 30(2), 99 -101. - Dixon, R. , Job, S. , Oliver, R. , Tompson, D. , Wright, J. G. , Maltby, K. , . . . & Taubel, J. (2008). Lamotrigine does not prolong QTc in a thorough QT/QTc study in healthy subjects. British journal of clinical pharmacology, 66(3), 396 -404.

Carbamazepi ne QT interval Drug concentration There is no evidence for QT prolongation with either topiramate or gabapentin. - Saetre, E. , Abdelnoor, M. , Amlie, J. P. , Tossebro, M. , Perucca, E. , Taubøll, E. , . . . & Gjerstad, L. (2009). Cardiac function and antiepileptic drug treatment in the elderly: A comparison between lamotrigine and sustained‐release carbamazepine. Epilepsia, 50(8), 1841 -1849. - Chen, D. , Lal, R. , Zomorodi, K. , Atluri, H. , Ho, J. , Luo, W. , . . . & Cundy, K. (2012). Evaluation of gabapentin enacarbil on cardiac repolarization: a randomized, doubleblind, placebo-and active-controlled, crossover thorough QT/QTc study in healthy adults. Clinical therapeutics, 34(2), 351 -362.

Trazodone R T P Q Mild QT prolongation S QT Interval - Levenson, J. L. (1999). Prolonged QT interval after trazodone overdose. American Journal of Psychiatry, 156(6), 969 a-970. - Dattilo, P. B. , & Nordin, C. (2007). Prolonged QT associated with an overdose of trazodone. The Journal of clinical psychiatry, 68(8), 1309. In overdose

Stimulants and Benzodiazepines Not linked to QT prolongation or torsade de pointes - Goodnick, P. J. , Parra, F. , & Jerry, J. (2002). Psychotropic drugs and the ECG: focus on the QTc interval. Expert opinion on pharmacotherapy, 3(5), 479 -498.

QT Prolongation with Acetylcholinesterase Inhibitors QT prolongation Torsade de pointes Older patients Significant medical comorbidity - Kitt, J. , Irons, R. , Al-Obaidi, M. , & Missouris, C. (2015). Case Report: A case of donepezil-related torsades de pointes. BMJ case reports, 2015.

QT Prolongation with Opioids Methadone Buprenorphine Strong association with QT prolongation and torsade Less likely to cause QT prolongation Has a potential to increase the QT interval - Abramson, D. W. , Quinn, D. K. , & Stern, T. A. (2008). Methadone-associated QTc prolongation: a case report and review of the literature. Primary care companion to the Journal of clinical psychiatry, 10(6), 470. - Wedam, E. F. , Bigelow, G. E. , Johnson, R. E. , Nuzzo, P. A. , & Haigney, M. C. (2007). QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial. Archives of internal medicine, 167(22), 2469 -2475. .

Key Points • Antiepileptic drugs do not cause significant QT prolongation. • Benzodiazepines and stimulants are also not linked to significant QT prolongation. • Methadone has been associated with QT prolongation and with torsade de pointes.

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