Complete heart block and death following lamotrigine overdose

French, L. Keith; McKeown, Nathanael J.; Hendrickson, Robert G.

doi:10.3109/15563650.2011.572555

Cited by 25 publications

(15 citation statements)

References 10 publications

(15 reference statements)

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“…Thus, the effect size of CBZ or LTG on cardiac contraction at typical therapeutic concentrations is likely to be lower in epilepsy patients. In the instance of a CBZ or LTG overdose, however, the inhibitory effects on contraction properties as well as on electromechanical coupling (as shown at 250 and 500 μM LTG) appear to be of clinical importance, as illustrated by previous case reports (24, 25). …”

Section: Discussionmentioning

confidence: 81%

“…Our findings may at least partially explain some of the cardiac disturbances, which were reported in epilepsy patients treated with AEDs in mono- or polytherapy. For instance, myocardial failure was reported in the context of CBZ intoxication (24, 43, 44), a complete atrioventricular block upon an overdose of LTG (25) and occurrence of sinus node dysfunction, atrial flutter/fibrillation, atrioventricular block, or ventricular tachycardia in association with the combined use of sodium channel-blocking AEDs (34, 35, 45, 46). …”

Section: Discussionmentioning

confidence: 99%

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Antiepileptic Drugs Impair Shortening of Isolated Cardiomyocytes

et al. 2017

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BackgroundMost antiepileptic drugs (AEDs) inhibit seizure generation by acting on voltage-dependent ion channels. Voltage-dependent sodium and calcium channels are commonly expressed in brain and heart, suggesting that AEDs may have considerable cardiodepressive effects, thereby facilitating sudden cardiac death as a potential cause of sudden unexpected death in epilepsy. Here, we investigated the effects of carbamazepine (CBZ), lamotrigine (LTG), and levetiracetam (LEV) alone and in combination on the shortening properties of isolated ventricular cardiomyocytes of wild-type mice.MethodsProperties of murine cardiomyocytes were determined by recording the sarcomere shortening with a video imaging system before, during, and after administration of AEDs in different concentrations and combinations. We assessed (i) the number of successful shortenings during continuous electrical stimulation (electromechanical coupling) and (ii) the shortening amplitude as well as other shortening-related properties upon repetitive electrical stimulation at 4 Hz. Data are given as mean ± SEM.ResultsAt 100 μM, CBZ (10 cells), LTG (11 cells), and LEV (11 cells) alone had no effect on the electromechanical coupling but reversibly reduced shortening amplitudes by 15 ± 4, 24 ± 3, and 11 ± 3%, respectively. Increasing the LTG concentration to 250 (21 cells) and 500 μM (4 cells) reversibly inhibited the electromechanical coupling in 62 and 100% of the experiments. Importantly, simultaneous application of CBZ, LTG, and LEV at 100 μM also impaired the electromechanical coupling in 8 of 19 cardiomyocytes (42%) and reduced the shortening amplitude by 21 ± 4%.ConclusionOur data show that AEDs reversibly impair cardiac excitation and contraction. Importantly, the blocking effect on electromechanical coupling appears to be additive when different AEDs are simultaneously applied. The translational value of these experimental findings into clinical practice is limited. Our results, however, suggest that rationale AED therapy may be important with respect to cardiac side effects and potential facilitation of serious cardiac dysfunction especially when AEDs are used in combination or at very high doses.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Antiepileptic Drugs Impair Shortening of Isolated Cardiomyocytes

et al. 2017

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“…LTG has had the most plausible effect in this case, as none of the proarrhythmic changes were observed in its absence on repeat testing, other situational factors being similar and despite a longer period of infusion/larger dose given. To further support this notion, there are reports in the literature where overdoses of LTG have led to QRS prolongation, complete heart block, and broad complex tachycardia 7, 8, 9. In addition, LTG, when compared with the SCB effects of flecainide, has shown similar reductions in the maximum rate of depolarization of the action potential in guinea pig Purkinje fibers 9 .…”

Section: Discussionmentioning

confidence: 94%

Proarrhythmogenic effects of lamotrigine during ajmaline testing for Brugada syndrome

Leong

Seligman

Varnava

2017

HeartRhythm Case Reports

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“…A clear relationship between clinical response, toxicity, and serum concentrations was not demonstrated because of the wide range of individual therapeutic levels reflecting the variability of the responses to lamotrigine treatment [5]. Overdoses of lamotrigine typically follow a benign course, but cases of lethal intoxication have been reported especially in combination with other drugs [22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Multidrug-related leukocytoclastic vasculitis raising suspicion of sexual homicide—things are not always what they seem

Tattoli

Krocker²,

Sautter³

et al. 2015

Int J Legal Med

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Ambiguous findings during external examination of a deceased in combination with dubious autopsy findings can raise doubts concerning the manner and cause of death. We report the case of a 35-year-old female deceased who had suffered from a borderline personality and depressive disorder with suicidal ideation. At the death scene, the body showed massive facial swelling accompanied by complete reddening of the skin of the face, with patchy skin abrasions on the forehead and neck, and purple bruise-like discolorations distributed symmetrically over both shoulders, elbows, hands, hips, knees, lower legs, and feet, raising the suspicion of underlying massive external blunt force injury. Police investigators strongly suspected sexual homicide. At autopsy, dissection in layers revealed massive subcutaneous hemorrhages as the cause of the reddish skin discolorations. Toxicological analyses showed fatal levels of lamotrigine with additional proof of zopiclone, zolpidem, diphenhydramine, Odesmethylvenlafaxine, pregabalin, tramadol, and modafinil in venous blood. Histologically, both the macroscopically impressive purple skin changes with underlying bleeding into the subcutaneous tissue and the skin abrasions were due to leukocytoclastic vasculitis, a form of acute hypersensitivity vasculitis that was a reaction to the multiple therapeutic drugs that the woman had taken shortly before death. The manner of death was classified as suicide, and sexual homicide was ruled out.

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Complete heart block and death following lamotrigine overdose

Cited by 25 publications

References 10 publications

Antiepileptic Drugs Impair Shortening of Isolated Cardiomyocytes

Antiepileptic Drugs Impair Shortening of Isolated Cardiomyocytes

Proarrhythmogenic effects of lamotrigine during ajmaline testing for Brugada syndrome

Multidrug-related leukocytoclastic vasculitis raising suspicion of sexual homicide—things are not always what they seem

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