Adverse Effects of Antiepileptic Drug Lamotrigine and Oral Implications: Case Report

Abstract

Here, we report on a patient who presented with extensive oral lesions. The treatment with lamotrigine is described.The patient presented with bilateral facial swellings and mental space swelling with actively draining extra oral sinus tract in the central chin area. Dental medicine professionals should be aware of the risks involved with using this medication, and should recognize the population at risk among patients suffering from epilepsy, bipolar and neurologic disorders.

Introduction

Lamotrigine is an antiepileptic medication used in the treatment of partial and generalized tonic-clonicseizures.The use of lamotrigine has increased in the past years (1, 2). This happens because lamotrigine is, along with other antiepileptic drugs, used in the treatment of bipolar disorderand neurologic disorders (2).The use of lamotrigine increases the risk of some mucocutaneous disorders in the population of patients recieving lamotrigine therapy. Among adverse reactions, maculopapular rashes are relativelly common (3-15%), and the most serious adverse effect of lamotrigine is development of potentially fatal Stevens–Johnson syndrome andtoxicepidermalnecrolysis (2-5).Adverse reactions are more common during the first two months of treatment with lamotrigine, if the dosage is increased too rapidly, and if valproate is co-administered (4, 6).

Thus, health care professionals, including dental medicine professionals, shouldbe aware of risks involved with using these drugs, and should recognize the population which is particularly at such a risk.

This article describes the case of a patient who presented with extensive oral lesions: (pseudomembranous, populous, bullous and erosive) after starting treatment with lamotrigine.

Case report

A 35-year old woman was referred to the Department of Endodontics and Restorative Dentistry, School of Dental Medicine, University of Zagreb, for endodontic treatment of teeth 42 and 41. The patient presented with bilateral facial swellings and mental space swelling with actively draining extra oral sinus tract in the central chin area. She was referred from the Department of Oral Medicine, School of Dental Medicine, University of Zagreb, where she had been treated for oral mucosa lesions (sublingual, palatal, buccal) with D-Panthenol solution and Garasone gtt for the past month and a half.Sialolithiasis was also considered, and upon radiologic examination it was excluded as the cause of facial swelling. At that stage the diagnosis of oral medicine specialist wasaphthouslike ulcerations and sialolithiasis in observationem.

Oral medicine specialist suggested that such oral manifestations could be adverse effects of lamotrigine drug, but at that stage, neuropsychiatric therapy was not changed.

A radiograph of mandibular incisors revealed extensive periradicular radiolucency around teeth 42 and 41 (Figure 1.). Erosive lesions could be seen on buccalmucosa and pseudomembranous lesions on sublingual mucosa (Figure 2). Medical history revealed autism, congenital heart malformation (ventricular-septal defect), Zoloft (sertralinum) and Lamal (lamotrigine) wasprescribed by a neuropsychiatrist.

Figure 1.

Digital panoramic radiograph made before endodontic treatment. A radiolucent lesion in the region 41, 42 can be seen (arrows)

Figure 2.

Extensive erosive lesions on buccal mucosa

Endodontic treatment of teeth 42 and 41 was performed. At next appointment, after 10 days, the extra oral sinus tract showed signs of healing. Slight concavity of the skin was present in the area of the healing extra oral opening. Nevertheless, the mental swelling remained, as well as bilateral buccal space swellings (Figure 3). Intraoral signs andsymptoms got worse. The buccal mucosa and lower lip mucosa presented with extensive erosive lesions (Figure 4). The patient complained about pain, burning, itching and a yellowish-watery discharge in the early morning hours.Control cone beam CT revealed extensive bone loss in 42, 41 region (Figure 5). The sinus tract was visualized: the purulent exudate has broken through the overlying cortical plate.

Figure 3.

Sinus tract is showing signs of healing 10 days from endodontic treatment.Mental swelling and bilateral buccal space swellings can be noticed

Figure 4.

Extensive erosive lesions on the lower lip mucosa

Figure 5.

Post endodontic CB-CT. Root canals of 41 and 42 are filled. Extensive bone loss is present around teeth 41 and 42

Lamotrigine was withdrawn from the patient’s therapy.

After one week, the swellings got much smaller, buccal lesions were healing (Figure 6),andpseudomembranous lesion at the lower lip mucosa got smaller (Figure 7).

Figure 6.

Healed lesions on buccal mucosa after cessation of lamotrigine therapy

Figure 7.

Healed lower lip mucosa after withdrawal of lamotrigine therapy

The patient was referred to the Department of Oral Medicine for follow up of oral mucosa lesions.

Discussion

Lower incisors, which were left open for a period of three months,were a source of infection of mental space. The aim of endodontic therapy at that point was to clean, shape and obturate the compromised teeth. The question remains whether those teeth were endodontic treatment candidates in the first place. The adverse effects of lamotrigine were interpreted as odontogenic abscesses. Dental history revealed that the patient had another three teeth extracted (45,47, 37) while on therapy with lamotrigine.

The interaction between lamotrigine and valproate is well documented, and it is recommended that the two drugs not be combined(4, 5, 7, 8).Kavitha et al. (5) reported on the case of a patient with painful ulcers in the mouth, bleeding lips, rashes throughout the body, and high fever (39°C) induced by a combination of lamotrigine and valproic acid (Stevens–Johnson syndrome).This is however not the case with sertraline which was prescribed to our patient. It is generally accepted that combined therapy of lamotrigine with sertraline should not increase the risk of toxic reactions to lamitrigine. Christensen et al. (9) evaluated pharmacokinetic interaction between sertraline and lamotrigine, and they concluded that the metabolism of lamotrigine in patients receiving lamotrigine with sertraline was slower compared with those receiving lamotrigine alone, but this was found not to be of clinical significance. Nevertheless, some studies suggest that simultaneous administration of these two drugs could result in elevating lamotrigine blood levels with toxicity symptoms development (10).

Increased use of lamotrigine and other antiepileptic drugs in treating psychiatric and neurological conditions other than epilepsy should be taken into consideration when treating dental patients, and much care should be given to medical history.