Safety of lamotrigine in paediatrics: a systematic review

BMJ Open. 2015 Jun 12;5(6):e007711. doi: 10.1136/bmjopen-2015-007711.

Abstract

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Abdominal Pain / chemically induced
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / adverse effects*
  • Child
  • Dizziness / chemically induced
  • Drug Therapy, Combination
  • Exanthema / chemically induced
  • Headache / chemically induced
  • Humans
  • Lamotrigine
  • Nausea / chemically induced
  • Triazines / administration & dosage
  • Triazines / adverse effects*
  • Vomiting / chemically induced

Substances

  • Anticonvulsants
  • Triazines
  • Lamotrigine