Lamotrigine

Observational studies

Among 11 316 patients in a postmarketing surveillance study that included 3994 patients followed for 6 months or longer, the main events leading to drug withdrawal were rash (n = 210), drowsiness (n = 74), nausea (n = 66), dizziness (n = 63), headache (n = 61), vomiting (n = 33), ataxia (n = 32), malaise (n = 29), and aggression (n = 26). Rare serious adverse events included Stevens–Johnson syndrome in 12 cases, neutropenia in 4, thrombocytopenia in 3, and disseminated intravascular coagulation in 2. Leukopenia, a meningitic reaction, acute renal insufficiency, hepatotoxicity, and a lupus-like reaction occurred in one patient each [ ].

In an open study, there were adverse events (details not given) in two of 30 patients with serum lamotrigine concentrations between 16 and 39 μmol/l, and in 5 of 11 patients with serum concentrations between 39 and 86 μmol/l [ ]. This is one of the few studies to have provided preliminary evidence for a relation between serum lamotrigine concentrations and the risk of adverse reactions.

The efficacy of lamotrigine as monotherapy has been studied retrospectively in 83 children (mean age 8.7 years) with focal epilepsy (n = 43), generalized epilepsy (n = 32), or not classified (n = 8) [ ]. The median follow-up period was 8 months (mean = 8.5). Rash was the most common adverse reaction, in five patients; two patients discontinued treatment. There were no cases of Stevens–Johnson syndrome.

Lamotrigine has been used as maintenance monotherapy for rapid-cycling bipolar disorder in 324 patients (open label) and 182 patients (double-blind) with rapid-cycling bipolar disorder [ ]. In all, 265 patients reported adverse events during the open phase. The most common adverse events (over 10%) were headache, infection, influenza, nausea, abnormal dreams, dizziness, and rash. During the double-blind phase 122 patients reported adverse events, equally with lamotrigine and placebo.

In 44 patients with profound mental retardation a retrospective assessment of adjunctive lamotrigine (272 mg/day) showed a significant reduction in seizure frequency from 10.1 to 5.8 seizures per month [ ]. There were no treatment-related changes in laboratory parameters, vital signs, or body weight, and no serious rashes. In three of five patients there was worsened self-injurious behavior, requiring drug withdrawal.

Lamotrigine has been studied in 32 children with epilepsy refractory for at least 1 year to other antiepileptic drugs [ ]. Adverse reactions were uncommon, and there were no rashes.

The efficacy and safety of lamotrigine have been prospectively evaluated in 41 children and young adults (aged 3–25 years) with drug-resistant partial epilepsies [ ]. Lamotrigine withdrawal was mainly due to lack of efficacy (46%); only two patients developed a transient rash, which did not require withdrawal.

Adverse reactions to lamotrigine have been surveyed retrospectively in 2701 patients in five tertiary referral epilepsy centers in the UK; 1326 were excluded because lamotrigine and/or comparators had been begun outside the study centers [ ]. The most common adverse events were rash (10%), dizziness, ataxia, and diplopia. There were four cases of life-threatening adverse events, one case each of hepatic insufficiency, acute exacerbation of ulcerative colitis, disseminated intravascular coagulation, and renal insufficiency caused by rhabdomyolysis and myoglobinuria. The mortality rate was 1.7 per 100 patient-years and the standard mortality ratio was 10.4, similar to other antiepileptic drugs (gabapentin and vigabatrin). No deaths were directly attributable to lamotrigine.

In an open randomized study in 417 patients over 2 years old who took lamotrigine or carbamazepine monotherapy for new-onset epilepsy there was similar efficacy (65% were free of seizures with lamotrigine and 73% with carbamazepine) [ ]. Although the patients taking lamotrigine tended to have fewer adverse events than those taking carbamazepine (52% versus 60%), the difference was not significant. Somnolence was the only adverse event reported at an incidence of over 5% and it was more frequent in patients taking carbamazepine (11% versus 4% with lamotrigine).

Comparative studies

In a 48-week, double-blind, monotherapy trial of 260 patients with newly diagnosed epilepsy, the proportion withdrawn because of adverse events was 11% those taking lamotrigine (9% with rash) and 21% in those taking carbamazepine (13% with rash). Somnolence was more frequent with carbamazepine (22% versus 12%), but the incidence of other common complaints (headache, weakness, rash, nausea, dizziness) did not differ between the groups [ ]. Although it was concluded that lamotrigine is tolerated better than carbamazepine, in this and other trials a design that involved twice-daily dosing may have placed carbamazepine at a disadvantage in the comparison.

In a multicenter, double-blind comparison of lamotrigine and phenytoin (titrated over 6 weeks from starting dosages of 100 and 200 mg/day respectively) in 181 patients with newly diagnosed epilepsy there were comparable seizure freedom rates and comparable trial discontinuation rates with the two drugs [ ]. Rashes leading to withdrawal occurred in 12% of patients assigned to lamotrigine and in 5% of those assigned to phenytoin, but the risk associated with lamotrigine might have been overestimated, owing to an excessively high starting dose. Central nervous system adverse reactions were more common with phenytoin, the difference being statistically significant for weakness (29% versus 16%), somnolence (28% versus 7%), and ataxia (12% versus 0%).

A review of the manufacturer’s safety database from the adult clinical trial program has been published [ ]. In placebo-controlled add-on trials involving a total of 1555 patients, the most common adverse events were dizziness (35% versus 15% on placebo), headache (26% versus 21%), diplopia (25% versus 6%), ataxia (20% versus 6%), nausea (19% versus 9%), blurred vision (14% versus 4%), rhinitis (11% versus 8%), somnolence (10% versus 7%), rashes (10% versus 5%), and vomiting (10% versus 5%). Dizziness and rashes were the most common causes of withdrawal, each in 2% of patients. Dizziness, diplopia, nausea, blurred vision, and headache occurred more commonly in patients co-medicated with carbamazepine than in those co-medicated with other drugs. In randomized comparative monotherapy studies, somnolence, weakness, dizziness, and ataxia occurred less often with lamotrigine than with carbamazepine or phenytoin, whereas insomnia was slightly more frequent with lamotrigine. Withdrawals due to adverse events were fewer with lamotrigine than with the other drugs. Rash associated with lamotrigine typically occurred within the first 8 weeks. Exceeding the currently recommended slow dosage escalation guidelines and co-administration of valproate are risk factors for rashes. In adults, the incidence of Stevens–Johnson syndrome was approximately 1:1000, but higher rates (1 in 50 to 1 in 300) have been reported in children [ , ].

In a multicenter, double-blind, monotherapy trial in 150 elderly patients with newly diagnosed epilepsy (mean age 77 years) lamotrigine (median dosage 100 mg/day) was better tolerated than carbamazepine (400 mg/day) [ ]. The drop-out rate for adverse events was 18% with lamotrigine compared with 42% with carbamazepine. Patients taking lamotrigine had a lower incidence of rashes (3% versus 19%), somnolence (12% versus 29%), and dizziness (10% versus 17%). Lamotrigine may be a better choice for initial treatment in elderly people, although the toxicity of carbamazepine might have been overestimated by giving a non-modified-release formulation twice daily. Seizure control was comparable with the two drugs, but statistical power was insufficient to demonstrate equal efficacy.

In 126 patients with carbamazepine-resistant or valproate-resistant epilepsy given lamotrigine, 50% during add-on therapy and 53% during lamotrigine monotherapy had at least 50% reduction in total seizures [ ]. There were adverse events in 49 patients, including respiratory tract infections (n = 11), dizziness (n = 8), headache (n = 7), diplopia (n = 5), tremor (n = 5), somnolence (n = 4), insomnia (n = 4), nausea (n = 4), and weakness (n = 3). Treatment was discontinued in nine patients because of adverse events, in five cases because of rash.

Cognitive adverse effects of lamotrigine and valproate have been compared in a double-blind, randomized, placebo-controlled study in 30 healthy volunteers who took lamotrigine 50 mg, valproic acid 900 mg, or placebo for 12 days [ ]. Lamotrigine had a relatively good cognitive profile but no different from that of valproic acid at the doses tested. Lamotrigine was associated with a selective general psychostimulant effect. As this study was performed in healthy volunteers taking a low dose, and conducted over a very short time, its conclusions are not generalizable to patients with epilepsy taking long-term treatment.

In a double-blind comparison of gabapentin and lamotrigine in 309 patients with new-onset partial or generalized seizures, the target doses were gabapentin 1800 mg/day and lamotrigine 150 mg/day [ ]. Severe adverse events were reported in 11% of patients taking gabapentin and 9.3% of patients taking lamotrigine. Two patients had serious adverse events thought to be related to the study drug; one took an overdose of gabapentin and the other had convulsions with lamotrigine. The most frequent treatment-related adverse events in both treatment groups were dizziness, weakness, and headache; 11% of patients taking gabapentin and 15% of those taking lamotrigine withdrew because of adverse events. There was an increase of over 7% in body weight from baseline in 14% of the patients taking gabapentin and 6.6% of those taking lamotrigine. There were benign rashes in 4.4% of those taking gabapentin and 11% of those taking lamotrigine.

During a 12-week, randomized, double-blind pilot trial lamotrigine was compared with citalopram in 20 patients with bipolar affective disorder, of whom 12 completed the study [ ]. One patient taking lamotrigine complained of dizziness and did not return for follow-up assessment. One patient discontinued because of hypomania and one because of worsening of symptoms.

The adverse reactions profiles of several antiepileptic drugs, including lamotrigine 300 mg/day, and several antipsychotic agents in the treatment of bipolar disorder have been reviewed, drawing data from randomized trials, open studies, and reviews [ ]. Adverse reactions to lamotrigine were: dizziness (31%), diplopia (24%), nausea (18%), vomiting (11%), blurred vision (11), ataxia (10%), and a benign rash (8%). In patients with bipolar disorder adverse reactions were less common, with the exception of headache.

In an open study of the use of lamotrigine (mean dose 132 mg/day for 8 weeks) as adjunctive or monotherapy in 20 adolescents with bipolar disorder during a depressive episode (n = 20) adverse reactions reported at any time included headache (84%), fatigue (58%), nausea (53%), sweating (47%), and sleep disturbances (11%) [ ]. There were no significant laboratory abnormalities after 8 weeks, no significant weight change, rash, or other significant adverse effects or reactions.

In about 100 patients with bipolar II disorder, randomized to lamotrigine or lithium, both drugs were effective, but lamotrigine had a better profile of tolerability [ ]. In a similar study in 34 patients with unipolar depression, there were no differences in tolerability between lamotrigine and lithium [ ].

In a small, open, randomized comparison of lamotrigine and sustained-release carbamazepine for the treatment of newly diagnosed symptomatic seizures after stroke in elderly people, lamotrigine was significantly better tolerated [ ].

Lamotrigine and sustained-release carbamazepine have been compared in a double-blind, parallel-group study in patients over 65 years old with newly diagnosed epilepsy who had had at least two unprovoked seizures [ ]. The trial lasted 40 weeks, with a 4-week dose escalation phase, during which doses were adjusted up to 500 mg/day for lamotrigine and 2000 mg/day for carbamazepine. The primary end-point was retention in the trial, which is a mixed measure of efficacy and tolerability; 68/93 (73%) and 61/92 (67%) of patients randomized to lamotrigine or carbamazepine respectively completed the study. There was a non-significant trend to higher seizure-free rates for carbamazepine and better tolerability for lamotrigine. Previous comparative studies in the same populations of elderly patients had shown significant findings in favor of better tolerability of lamotrigine. The explanation for this partial discrepancy may be that because a sustained-release formulation of carbamazepine was used initial target dosages were lower and carbamazepine titration was slower.

In a double-blind comparison of lamotrigine 100 mg bd and amitriptyline 50 mg/day in 53 patients with diabetic neuropathy, the two drugs had equal efficacy and favorable tolerability [ ].

Placebo-controlled studies

The analgesic efficacy of lamotrigine in painful HIV-associated distal sensory polyneuropathy has been studied, given anecdotal reports of its efficacy, in a randomized, double-blind, placebo-controlled study [ ]. Of 42 subjects, 13 did not complete the 14-week study. Of those who took lamotrigine five dropped out because of rashes and one because of a gastrointestinal infection. The rashes were mild or moderate morbilliform rashes and resolved after withdrawal.

There were positive effects on cognitive function and no adverse reactions in a double-blind, placebo-controlled study in a small population of patients with schizophrenia in which lamotrigine was added to clozapine [ ].

Systematic reviews

In an analysis of five double-blind, randomized, placebo-controlled trials in the acute treatment of bipolar depression, lamotrigine monotherapy was not effective [ ]. The incidences of mania, hypomania, or mixed episodes were low and did not differ between lamotrigine and placebo. Lamotrigine did not precipitate or worsen manic symptoms.

The potential role of lamotrigine in patients with schizophrenia resistant to atypical antipsychotic drugs has been evaluated in several studies. In an analysis of two multicenter, double-blind, placebo-controlled, parallel-group studies of a flexible dose of lamotrigine 100–400 mg/day as add-on treatment in more than 400 patients with schizophrenia and stable residual psychotic symptoms there were similar percentages of adverse effects in the two groups [ ]. Serious adverse events were reported by three patients who took placebo and 11 who took lamotrigine; they mainly concerned worsening of psychiatric symptoms. Only one serious adverse event, a suicide attempt, was considered to be possibly related to lamotrigine.

Nervous system

The most common adverse reactions to lamotrigine include dizziness, weakness, headache, diplopia, ataxia, blurred vision, and somnolence [ ]. These effects resemble those seen with carbamazepine and can result from an adverse pharmacodynamic interaction. Tolerability is better when lamotrigine is given as monotherapy or with drugs other than carbamazepine; however, tremor develops in some patients taking valproate in combinations [ ]. During monotherapy, serum lamotrigine concentrations associated with intolerable adverse effects (mostly headache, dizziness, and ataxia) were 0.4–18.5 μg/ml and overlapped widely with those tolerated in other patients [ ].

Irritability and aggressive behavior occur occasionally, and mentally retarded patients are possibly at greater risk [ ]. Rare central nervous system effects include insomnia, psychosis [ ], downbeat nystagmus [ ], movement disorders [ , ], and a Tourette-like syndrome. Lamotrigine can increase seizure frequency and severity in children with severe myoclonic epilepsy [ ].

• A 47-year-old man developed a rash, fever, and rigors after taking lamotrigine (50 mg/day at maintenance) for 1 month [ ]. The reaction subsided after withdrawal, but 3 days later he complained of left shoulder pain and numbness in the left arm. The pain worsened over the next 3 weeks and then subsided. Thereafter, he developed weakness of the left arm with muscle wasting and signs of denervation in the biceps, infraspinatus, and supraspinatus. The condition was diagnosed as neuralgic amyotrophy. Almost complete recovery occurred over 8 months.

It is possible that the initial hypersensitivity reaction in this case determined focal neuronal involvement at the brachial plexus.

Ballismus has been associated with lamotrigine in a patient with epilepsy [ ].

• A 17-year-old boy with a long history of intractable secondarily generalized tonic–clonic seizures and a normal MRI scan took lamotrigine 25 mg/day initially and gradually increased the dose to 200 mg/day. His epileptic seizures were significantly improved. After 5 days he developed involuntary, continuous, jerky movements of all four limbs, gradually worsening to the point of causing excoriation and bruising of the legs and impaired walking. The disorder, which was thought to be consistent with bilateral ballismus, disappeared about 10 days after withdrawal of lamotrigine.

Two cases of aseptic meningitis have been attributed to lamotrigine [ ]. In the first case it had been prescribed for prevention of seizures in an HIV-positive patient. In the second, it had been substituted for valproic acid in a pregnant woman with epilepsy.

Myoclonus provoked by lamotrigine has been described in a patient with bipolar affective disorder [ ].

Psychological

The cognitive and behavioral effects of lamotrigine 150 mg/day have been compared with those of carbamazepine 696 mg/day in 25 healthy adults in a double-blind, crossover, randomized study with two 10-week treatment periods [ ]. Lamotrigine had significantly fewer cognitive and behavioral adverse effects than carbamazepine, and 48% of the variables favored lamotrigine. The differences encompassed cognitive speed, memory, graphomotor coding, neurotoxic symptoms, mood, sedation, perception of cognitive performance, and other quality-of-life perceptions. The cognitive and behavioral changes favored lamotrigine over carbamazepine, but the magnitude of the observed effects was modest, although it could be relevant in some patients.

The cognitive effects of lamotrigine compared with topiramate as add-on therapy in adults with epilepsy have been studied in a multicenter, double-blind, randomized, trial [ ]. Lamotrigine or topiramate was introduced in addition to carbamazepine or phenytoin and titrated over 8 weeks to target doses. During the maintenance phase, the average daily dose of lamotrigine was 494 mg and the average daily dose of topiramate was 299 mg. The primary end-point was a change from screening to the end of the maintenance phase in a combined analysis of standardized measures of cognition. For the primary end-point, cognitive performance at the end of the maintenance phase was better with lamotrigine than with topiramate. The cognitive complaints reported as adverse events in this study are shown in Table 1 . The frequencies of cognitive adverse events and of premature withdrawals related to cognitive decline were higher with topiramate than with lamotrigine (6% versus 0%).

The effect of lamotrigine on cognition in 61 children with well-controlled or mild epilepsy has been studied in a double-blind, placebo-controlled, crossover study [ ]. They were randomly assigned to add-on therapy with either lamotrigine followed by placebo or placebo followed by lamotrigine. Each treatment lasted 9 weeks and the crossover period was 5 weeks. Seizure frequency was similar during the two phases. There were no significant differences in various neuropsychological tests between placebo (n = 52) and lamotrigine (n = 59). The following adverse events were reported: coryza or other viral illness (lamotrigine 9; placebo 9), rash (7 versus 2), nausea (5 versus 2), injury or accident (4 versus 0), pharyngitis (4 versus 1), headache (1 versus 2), dizziness (1 versus 2), abdominal pain (0 versus 2). Some patients were withdrawn (6 versus 0); five of the withdrawals were due to a rash and one was due to nausea and dizziness. Treatment-related adverse effects were observed in 39% of the patients with lamotrigine and in 37% with placebo; all were mild and transient.

Psychiatric

Three patients (2 men, one woman) with bipolar or schizoaffective disorders developed signs and symptoms of mania shortly after starting lamotrigine 100–200 mg/day; after reduction of lamotrigine the manic symptoms disappeared [ ]. The authors concluded that lamotrigine may act as a rapid antidepressant and that provocation of mania is related to the dosage and the rate of titration.

Of about 1400 patients with epilepsy taking lamotrigine, six developed a psychotic disorder, mainly, but not exclusively, consisting of paranoid–hallucinatory (“schizophrenia-like”) symptoms [ ]. A clear cause and effect relationship could not be determined because of the retrospective nature of the data, even though there was rapid remission of the psychotic symptoms after dosage reduction or withdrawal. Lack of a history of previous psychotic episodes in all cases but one made the author consider that these disorders were de novo psychoses.

Lamotrigine can cause positive psychotic symptoms in patients with epilepsy or bipolar disorder, and can exacerbate positive psychotic symptoms in patients with schizoaffective disorder. In two cases positive symptoms in paranoid schizophrenia were exacerbated [ ].

There have been sporadic cases of delirium, hallucinations, and mania in patients taking lamotrigine for various psychiatric conditions [ ].

Endocrine

In two children with cranial diabetes insipidus, desmopressin requirements fell while they were taking lamotrigine [ ]. Lamotrigine may act at voltage-sensitive sodium channels and reduce calcium conductance. Both of these mechanisms of action are shared by carbamazepine, which can cause hyponatremia secondary to inappropriate secretion of antidiuretic hormone.

Metabolism

In a prospective evaluation of the effect of lamotrigine 3.5–14.2 mg/kg on growth in 103 children and adolescents aged 1.6–16 years with epilepsy treated with lamotrigine monotherapy for 6–71 months, the children had normal growth, although the study had several methodological shortcomings [ ].

The effect of lamotrigine, lithium, and placebo on weight in obese and non-obese patients with bipolar disorder has been investigated in a post-hoc analysis of two double-blind, placebo-controlled, 18-month studies [ ]. Mean changes in weight among obese patients (n = 155) at week 52 were − 4.2, + 6.1, and − 0.6 kg with lamotrigine, lithium, and placebo respectively. Among non-obese patients (n = 399) mean changes in weight at week 52 were 0.5, + 1.1, and + 0.7 kg respectively, with no significant differences. The authors concluded that obese patients with bipolar I disorder lose weight while taking lamotrigine and gain weight while taking lithium.

The effect of lamotrigine on body weight has been assessed retrospectively using data from two double-blind, placebo-controlled and lithium-controlled, 18-month studies in patients with bipolar I disorder (n = 227 for lamotrigine, 190 for placebo, 166 for lithium) [ ]. Lamotrigine was associated with stable body weight during 1 year of treatment and was comparable to placebo in mean weight change, incidence of clinically significant weight change, and incidence of weight changes reported as adverse events in patients with bipolar disorder.

Hematologic

Aplastic anemia occurred in one patient who had recovered 7 years earlier from bone-marrow aplasia ascribed to carbamazepine [ ]. Severe pure red cell aplasia in a patient with heterozygous beta-thalassemia reversed rapidly after lamotrigine withdrawal; however, lamotrigine did not affect hematology parameters in another patient with the same condition [ ]. In two other cases of anemia associated with increased platelet counts the role of lamotrigine could not be ascertained [ ].

There have been a few reports of leukopenia or neutropenia, and one case of septic shock secondary to leukopenia possibly due to lamotrigine [ ].

• An 11-year-old girl with congenital left renal agenesis, epilepsy from cortical dysgenesis, and chronic hepatitis B and C, developed a rash and agranulocytosis (white cell count 3.1 × 10 ⁹ /l, lymphocytes 92%, and monocytes 8%) 15–20 days after starting to take lamotrigine [ ]. She recovered rapidly after drug withdrawal.

An inappropriately high starting dose (50 mg/day) may have contributed to this reaction.

Lamotrigine has been associated with agranulocytosis [ ].

• A 59-year-old woman, with seizures after resection of a low-grade glioma, chemotherapy, and radiotherapy 2 years before, took lamotrigine 300 mg/day for 9 weeks and developed an agranulocytosis. The lamotrigine serum concentration was 2.2 μg/ml (usual target range 1–15 μg/ml). A bone marrow biopsy showed a hypocellular marrow with reduced myelopoiesis, a shift to the left, and normal cytogenetics. Over the next few days she developed a fever but no infection. She recovered after 10 days, having been given granulocyte-colony-stimulating factor and prophylactic antibiotics for 7 days.

• A 29-year-old woman with Blackfan–Diamond anemia developed an erythroblastopenic crisis after taking phenytoin on two separate occasions and then again after taking lamotrigine [ ]. The proposed mechanism was inhibition of dihydrofolate reductase, and the crisis responded to treatment with folinic acid. Lamotrigine was then continued without ill effect.

• Reversible agranulocytosis developed in a 30-year-old woman who had taken lamotrigine 100 mg/day for 6 weeks and valproate 250 mg/day for 2 weeks [ ]. Her white cell count fell from 6.7 × 10 ⁹ /l at 4 weeks to 2.6 × 10 ⁹ /l at 6 weeks and the absolute neutrophil count was 580 × 10 ⁶ /l. The white cell count recovered after withdrawal of lamotrigine; the valproate was continued.

A hemophagocytic syndrome has been attributed to lamotrigine in a high initial dose [ ].

• A 4-year-old boy with cerebral palsy and epilepsy was treated with primidone 375 mg/day and valproic acid 500 mg/day. Since his seizures were not controlled, lamotrigine 250 mg day (16 mg/kg) was added, and 3 weeks later he developed an intermittent fever and a rash. He became comatose and had generalized tonic–clonic seizures, with marked hepatosplenomegaly. He had a low white blood cell count (2.1 × 10 ⁹ /l) and a low hemoglobin concentration, and a low platelet count. Liver function and renal function were abnormal. A bone marrow biopsy showed hemophagocytosis. He was given intravenous immunoglobulin and glucocorticoids and his liver function, renal function, and pancytopenia resolved within 2 weeks.

Mouth

Mouth ulcers occurred in two patients taking lamotrigine in whom oxcarbazepine had been withdrawn some weeks before the observation of the supposed adverse reaction [ ]. The authors speculated that de-induction may have contributed to the pathogenesis of this adverse effect.

Liver

Liver toxicity from lamotrigine is extremely rare. Acute hepatic necrosis occurred in the context of a hypersensitivity reaction that also involved the skin [ ].

Four children developed reversible lamotrigine-associated hepatotoxicity [ ]. One had pre-existing encephalitis and the other three had multiple medical and neurological problems, fever and infections, were taking many other drugs, and had very frequent seizures; two had epilepsia partialis continua. The information given was insufficient to assess the role of lamotrigine in the pathogenesis of the hepatic dysfunction.

Reversible hepatotoxicity occurred in three children taking lamotrigine [ ]. In one there was severe hepatic failure. The liver abnormalities resolved after withdrawal.

Lamotrigine-induced hepatitis is considered to be immune-mediated, and is often part of an anticonvulsant hypersensitivity syndrome. A patient with a history of schizophrenia taking lamotrigine 200 mg/day and aripiprazole 15 mg/day developed acute hepatitis, which was considered probably due to lamotrigine [ ]. Other cases have been described [ ].