The Assessment of Cardiac Risk in Patients Taking Lamotrigine; A Systematic Review

Friday, November 11, 2022

2:15 PM – 3:45 PM

Location: Room 209-211

Presenting Author(s)

JR

Judith Restrepo, MD

Psychiatrist
Massachusetts General Hospital
Boston, Massachusetts

PDF

Co-Author(s)

RM

Rachel MacLean, MD

Resident
Massachusetts General Hospital
Boston, Massachusetts
Scott R. Beach, MD, FACLP

Psychiatrist
Massachusetts General Hospital
Boston, Massachusetts
JH

Jeff Huffman, MD

Professor of Psychiatry
MGH
LEXINGTON, Massachusetts
Christopher Celano, MD, FACLP

Associate Director, Cardiac Psychiatry Research Program
Massachusetts General Hospital
Boston, Massachusetts
James Januzzi, MD

Cardiologist
Massachusetts General Hospital
Boston, Massachusetts

Abstract:

Objective: In October 2020, the Food and Drug Administration (FDA) issued a warning advising against the use of lamotrigine in patients with cardiac conduction disorders, prior ventricular arrhythmias, or cardiac disease, based on in vitro data.^1,2 We are not aware of any reviews that have examined the full body of evidence regarding lamotrigine’s cardiac risk profile in healthy individuals or those with underlying cardiac disease. Significantly increased psychiatric morbidity was observed following the FDA’s warning regarding QTc prolongation with citalopram, which led to widespread reflexive dose reduction.^3,4 Unnecessary discontinuation of lamotrigine in established patients may have substantial adverse consequences.⁵ Finally, understanding lamotrigine’s cardiac risk may inform future investigations within its class.

Method: We conducted a systematic review of Web of Science and PubMed for valid measures of cardiac function (including heartrate, ECGs, and laboratory values) among patients taking lamotrigine. For each study, we defined the study sample, screening process, and outcomes.

Results: Seven randomized controlled trials (RCTs), 7 nonrandomized observational studies, and 24 case reports were identified. Among young, healthy individuals taking therapeutic doses of lamotrigine, no ECG changes were reported. One RCT in older patients found small increases in QRS and PR intervals of unclear clinical significance. Case reports documented QRS widening, Brugada syndrome (BrS), QTc prolongation and sudden cardiac death in patients taking lamotrigine, though many patients had consumed toxic quantities of lamotrigine and/or co-ingested other medications.

Conclusions: Evidence suggests that the FDA’s warning regarding lamotrigine use among patients with cardiac disease is too broad. Lamotrigine use at therapeutic doses may be associated with modest QRS widening, though these changes are likely only clinically significant in overdose.

References:

1. FDA. Studies show increased risk of heart rhythm problems with seizure and mental health medicine lamotrigine (Lamictal) in patients with heart disease. FDA Drug Saf Commun. Published online 2021. https://www.fda.gov/drugs/drug-safety-and-availability/studies-show-increased-risk-heart-rhythm-problems-seizure-and-mental-health-medicine-lamotrigine

2. Lamictal (lamotrigine) [package insert]. Research Triangle Park, NC: GlaxoSmithKline. Published online 2015.

3. Gerlach LB, Kales HC, Maust DT, ym. Unintended consequences of adjusting citalopram prescriptions following the 2011 FDA warning. Am J Geriatr psychiatry. 2017;25(4). doi:10.1016/j.jagp.2016.11.010

4. Gerlach LB, Kim HM, Yosef M, Kales HC, Henry J, Zivin K. Electrocardiogram monitoring after the Food and Drug Administration warnings for citalopram: unheeded alerts? J Am Geriatr Soc. 2018;66(8). doi:10.1111/jgs.15420

5. Begley CE, Annegers JF, Swann AC, ym. The lifetime cost of bipolar disorder in the US: an estimate for new cases in 1998. Pharmacoeconomics. 2001;19(5 Pt 1). doi:10.2165/00019053-200119050-00004