Case Files of the University of California San Francisco Medical Toxicology Fellowship: Lamotrigine Toxicity

Abstract

A 56-year-old man was brought to the emergency department (ED) after he was found seizing on the floor by his family. His brother described hearing a thump in his room and witnessed him having a full body clonic seizure that lasted approximately 2 min. When emergency medical service arrived, he was found on the floor with altered mental status and with signs of facial trauma. No medications were administered en route to the hospital.On arrival to the ED, he was initially confused and mumbling incoherently. He was noted to be only oriented to self, and would not reliably follow commands. Approximately 1 h after arrival, he became agitated, seemed more confused, and would not follow any commands. Initial vital signs were: blood pressure, 147/76 mmHg; pulse, 81/min; respiratory rate, 18/min; temperature, 35°C by tympanic measurement; and oxygen saturation was 100% on room air. On physical exam, his pupils were 4 mm and reactive bilaterally. Extraocular movements appeared intact by observation only and there was no nystagmus. He had a nasal deformity and laceration to the right side of his tongue. The chest exam was normal with the exception of a large median sternotomy scar. His abdomen was soft, nontender, and there were no signs of bladder distension. Bowel sounds were noted to be present. There was no evidence of bowel or bladder incontinence. The neurological exam was notable for decreased attention, inability to follow commands, inability to repeat examiner's phrases, and markedly reduced language skills. The patient had spastic muscle tone with resistance to motion both with flexion and extension of all extremities. Deep tendon reflexes were noted to be 2+ in bilateral upper extremities and 3+ in bilateral lower extremities without clonus.

Correlation of elevated lamotrigine and levetiracetam serum/plasma levels with toxicity: A long-term retrospective review at an academic medical center

“…Our overall findings and adverse events are similar to what has been described in the literature for lamotrigine toxicity [ [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] ], although we did not have any fatalities attributed to lamotrigine. Lamotrigine toxicity primarily affects the neurologic and cardiac systems.…”

“…Lamotrigine also shows the property of auto-induction of metabolism so that dose adjustments are needed to maintain therapeutic levels. In published case series and retrospective reviews, lamotrigine overdose is typically benign, but serious toxicity including death and cardiac arrhythmias have been reported in some cases [ [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] ]. Adverse effects have been reported to increase significantly when serum/plasma levels exceed 14 milligrams per liter (mg/L) but vary by individual [ 2 ].…”

A Literature Review of the Use of Sodium Bicarbonate for the Treatment of QRS Widening

“…Sharma et al describe three cases of diphenhydramine toxicity with maximum QRS values ranging from 102 to 162 msec treated effectively with sodium bicarbonate [65]. Lamotrigine has also been implicated in causing sodium channel blockade and has also been shown to be responsive to sodium bicarbonate therapy [4,5]. Propoxyphene toxicity can also result in QRS widening and sodium channel blockade.…”

“…It is most widely known for its use in tricyclic antidepressant (TCA) toxicity. However, there are case reports of sodium bicarbonate therapy being used to treat QRS widening on the electrocardiogram (ECG) after a wide range of exposures including citalopram, cocaine, flecainide, diphenhydramine, propoxyphene, and lamotrigine [1][2][3][4][5][6][7][8]. The mechanism for its efficacy has not been fully elucidated, and it may differ depending on the drug responsible for toxicity.…”

Rash and multiorgan dysfunction following lamotrigine: could genetic be involved?

“…DHS is clearly different from LTG dose-dependent toxicity, which manifests mainly with alterations of mental status and neurological and cardiovascular symptoms [5]. It is considered instead to be an idiosyncratic reaction, which results from a chemotoxic and/or immunologically-mediated injury characterized by bio-activation of antiepileptic drugs and histocompatibility complex-mediated activation of T cells.…”