Safety of lamotrigine in paediatrics: a systematic review

OBJECTIVES To identify adverse drug reactions associated with lamotrigine in children and compare the safety profile with other antiepileptic drugs. SETTING Databases EMBASE (1974-April 2015), MEDLINE (1946-April 2015), PubMed and the Cochrane library for randomised controlled trials were searched for studies on safety of lamotrigine. PARTICIPANTS All studies involving paediatric patients aged ≤ 18 years who have received at least a single dose of lamotrigine with safety as an outcome measure were included. PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome measure was safety of lamotrigine. Drug interaction of lamotrigine was the secondary outcome. RESULTS A total of 78 articles involving 3783 paediatric patients were identified. There were 2222 adverse events (AEs) reported. Rash was the most commonly reported AE, occurring in 7.3% of the patients. Stevens-Johnson syndrome was rarely reported, with a risk of 0.09 per 100 patients. Discontinuation due to an adverse drug reaction (ADR) was recorded in 72 children (1.9% of all treated patients). Fifty-eight per cent of treatment discontinuation was attributed to different forms of rash and 21% due to increased seizures. Children on lamotrigine monotherapy had lower incidences of AEs. Headache (p=0.02), somnolence (<0.001), nausea (p=0.01), vomiting (p<0.001), dizziness (p<0.001) and abdominal pain (p=0.01) were significantly lower among children on monotherapy. CONCLUSIONS Rash was the most common ADR of lamotrigine and the most common reason for treatment discontinuation. Children receiving polytherapy have a higher risk of AEs than monotherapy users. TRIAL REGISTRATION NUMBER CRD42013006910.