Psych · Psychopharmacology — drug interactions and QTc
Drug interactions and QTc
Also known as QTc prolongation psychotropics · Drug-induced long QT · Torsades de pointes psychiatry · CYP interactions antipsychotics · Smoking clozapine CYP1A2 · Psychotropic polypharmacy interactions
Exam-exhaustive fellowship reference on psychotropic drug–drug interactions and QTc risk — PK vs PD framework, CYP1A2/2D6/3A4 maps, smoking–clozapine, fluvoxamine, QTc measurement and thresholds, TdP, high-risk agents, ECG monitoring, polypharmacy, and special populations. FRANZCP-primary, globally tagged.
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Target exams
Red flags
- Syncope, near-syncope or seizure-like collapse on QTc-risk psychotropics — treat as possible TdP until proven otherwise
- QTc approaching or exceeding 500 ms, or rise of about 60 ms from baseline — stop or switch culprits, fix electrolytes, monitor
- New fluvoxamine, ciprofloxacin or smoking cessation on clozapine without dose/level plan — toxicity risk
- Stacking multiple QT-prolonging drugs (antipsychotic + methadone + macrolide/quinolone) in a hypokalaemic patient
- Unexplained polymorphic VT — IV magnesium, stop QT drugs, ACLS; do not add further QT-prolonging antiarrhythmics blindly
- Citalopram/escitalopram above labelled max doses or with other QT drugs and risk factors
Meet the patient
A 78-year-old woman on the medical ward is treated for pneumonia. Her chart reads: citalopram 20 mg daily for two years, a thiazide, clarithromycin started yesterday, and ondansetron for nausea. Overnight she has a brief collapse with no prodrome and a facial laceration. The night registrar records "probable vasovagal, for reassurance".[8][16][17]
Her potassium is 3.1. Four QT-relevant exposures have accumulated on one drug chart, and nobody ordered an ECG. This is how psychiatric patients die of a treatable, entirely predictable problem.[4][16][17]
References22ShowHide
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- [2]Ray WA, Chung CP, Murray KT, et al. Atypical antipsychotic drugs and the risk of sudden cardiac death N Engl J Med, 2009.PMID 19144938
- [3]Reilly JG, Ayis SA, Ferrier IN, et al. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients Lancet, 2000.PMID 10744090
- [4]Roden DM Drug-induced prolongation of the QT interval N Engl J Med, 2004.PMID 14999113
- [5]Harrigan EP, Miceli JJ, Anziano R, et al. A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition J Clin Psychopharmacol, 2004.PMID 14709949
- [6]Beach SR, Celano CM, Noseworthy PA, et al. QTc prolongation, torsades de pointes, and psychotropic medications Psychosomatics, 2013.PMID 23295003
- [7]Funk MC, Beach SR, Bostwick JR, et al. QTc Prolongation and Psychotropic Medications Am J Psychiatry, 2020.PMID 32114782
- [8]Castro VM, Clements CC, Murphy SN, et al. QT interval and antidepressant use: a cross sectional study of electronic health records BMJ, 2013.PMID 23360890
- [9]Funk KA, Bostwick JR A comparison of the risk of QT prolongation among SSRIs Ann Pharmacother, 2013.PMID 24259697
- [10]Hasnain M, Vieweg WV QTc interval prolongation and torsade de pointes associated with second-generation antipsychotics and antidepressants: a comprehensive review CNS Drugs, 2014.PMID 25168784
- [11]Rostami-Hodjegan A, Amin AM, Spencer EP, et al. Influence of dose, cigarette smoking, age, sex, and metabolic activity on plasma clozapine concentrations: a predictive model and nomograms to aid clozapine dose adjustment and to assess compliance in individual patients J Clin Psychopharmacol, 2004.PMID 14709950
- [12]Hiemke C, Weigmann H, Härtter S, et al. Elevated levels of clozapine in serum after addition of fluvoxamine J Clin Psychopharmacol, 1994.PMID 7962687
- [13]Spina E, de Leon J Metabolic drug interactions with newer antipsychotics: a comparative review Basic Clin Pharmacol Toxicol, 2007.PMID 17214606
- [14]Spina E, Trifirò G, Caraci F Clinically significant drug interactions with newer antidepressants CNS Drugs, 2012.PMID 22171584
- [15]Kroon LA Drug interactions with smoking Am J Health Syst Pharm, 2007.PMID 17823102
- [16]Drew BJ, Ackerman MJ, Funk M, et al. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation Circulation, 2010.PMID 20142454
- [17]Tisdale JE, Jaynes HA, Kingery JR, et al. Development and validation of a risk score to predict QT interval prolongation in hospitalized patients Crit Care Med, 2013.PMID 23716032
- [18]Krantz MJ, Martin J, Stimmel B, et al. QTc interval screening in methadone treatment Ann Intern Med, 2009.PMID 19153406
- [19]Yap YG, Camm AJ Drug induced QT prolongation and torsades de pointes Heart, 2003.PMID 14594906
- [20]Vandenberk B, Vandael E, Robyns T, et al. Which QT Correction Formulae to Use for QT Monitoring? J Am Heart Assoc, 2016.PMID 27317349
- [21]Hiemke C, Bergemann N, Clement HW, et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017 Pharmacopsychiatry, 2018.PMID 29390205
- [22]Fanoe S, Kristensen D, Fink-Jensen A, et al. Risk of arrhythmia induced by psychotropic medications: a proposal for clinical management Eur Heart J, 2014.PMID 24644307