Lamotrigine adverse events

In an open study, there were adverse events (details not given) in two of 30 patients with serum lamotrigine concentrations between 16 and 39 pmol/1, and in 5 of 11 patients with serum concentrations between 39 and 86 pmol/1 (3). This is one of the few studies to have provided preliminary evidence for a relation between serum lamotrigine concentrations and the risk of adverse effects. 

Lamotrigine has been nsed as maintenance monotherapy for rapid-cycling bipolar disorder in 324 patients (open label) and 182 patients (donble-bUnd) with rapidcycling bipolar disorder (5). In aU, 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 donble-bUnd phase 122 patients reported adverse events, eqnaUy with lamotrigine and placebo. 

In a 48-week, double-blind, monotherapy trial of 260 patients with newly diagnosed epilepsy, the proportion withdrawn because of adverse events was 11% in the lamotrigine group (9% with rash) and 21% in the... 

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 (15). 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. 

Wong IC, Mawer GE, Sander JW. Adverse event monitoring in lamotrigine patients a pharmacoepidemiologic study in the United Kingdom. Epilepsia 2001 42(2) 237-44. 

Lamotrigine is reported to be generally well tolerated in maintenance studies, with the most common adverse events being headache, nausea, insomnia, and, to a lesser extent, tremor. Incidences of diarrhea and tremor are lower with lamotrigine than with litbium. 

Comparative studies Carbamazepine versus lamotrigine Carbamazepine and lamotrigine have been compared in 125 elderly patients with epilepsy using the modified Side Effect and Life Satisfaction Inventory and the Liverpool Adverse Event Profile in an international double-blind study [4 ]. Neither drug caused significant changes in health-related quality of life after 40 weeks. A borderline difference in the Side Effect and Life Satisfaction Inventory Dysphoria subscores favored lamotrigine. 

Drug formulations In a retrospective analysis of the effects of switching from branded to generic lamotrigine [193 in 13 of 285 patients, 6 had relapses and 3 had new adverse reactions. Compared with matched controls, the risk of loss of seizure control was significantly increased and adverse events were three times more frequent. Consecutive determinations of serum concentrations suggested that these complications were related to pharmacokinetic changes. 

In a randomized, blind-rater 16-week comparison in 90 patients, lithium and lamotrigine were associated with similar significant improvements over baseline, but the early drop-out rate was high at 42% [13 f. Adverse events were more common in those taking lithium than in those taking lamotrigine (Table 1). 

Observational studies Lamotrigine has been evaluated in a study that included an open, 1-week screening phase, a 20-week escalation phase, and a 12-week maintenance phase in 54 children aged under 13 years who had newly diagnosed absence epilepsy and had not previously been treated with antiepileptic drugs [138 ]. Rash was reported in six patients (11%), urticaria in one patient (2%), and pruritus in two patients (4%). None of these events was serious or resulted in premature withdrawal. Three patients had adverse events that led to premature withdrawal increased seizure activity in one, tremor in one, and vomiting and dizziness in one patient. 

In a retrospective study of lamotrigine monotherapy for seizure control in 72 children and adolescents with epilepsy, the mean follow-up period was 33 months [139. In six patients lamotrigine was withdrawn because of adverse events (rash 4, low white cell count 1, severe sleepiness 1). Rashes occurred 2-3 weeks after the start of therapy in four patients. 

In 204 infants (aged 1-24 months) with partial seizures who had been previously given lamotrigine in a randomized, double-blind, placebo-controUed study and who were followed in a long-term study for at least 24 weeks, the only adverse event that was thought to be attributable to the drug was irritability (n = 10) [140 ]. There were no cases of serious rash. 

Placebo-controUed studies In a 16-week, double-blind, placebo-controlled, flexible-dose study of lamotrigine in binge-eating disorder associated with obesity, 51 outpatients were randomized to either lamotrigine (n = 26) or placebo (n = 25) [146 ]. Four patients withdrew because of adverse events (lamotrigine, n = 3 placebo, n = 1), the most common of which were headache (35% versus 28%), insomnia (35% versus 20%), somnolence (27% versus 8%), rash (15% versus 12%), and dry mouth (15% versus 0%). 

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