Lamotrigine + Sertraline - Drug Interactions

A report describes two cases,which suggest that sertraline mayincrease lamotrigine levels and cause toxicity.

Clinical evidence,mechanism, importance and management

A patient’s lamotrigine levels were found to have doubled and symptoms of toxicity were noted (confusion,cognitive impairment) 6 weeks after sertraline 25mg daily was started (See reference number 1). The lamotrigine dose was halved, and sertraline dose titrated to 50mg daily. Symptoms of toxicity resolved, but lamotrigine levels were still 24 % higher than before sertraline was started. In another patient taking sertraline and lamotrigine with signs of lamotrigine toxicity, a 33 % reduction in sertraline dose resulted in a halving of lamotrigine level even though lamotrigine dose was increased by 33%.

The authors suggest that sertraline may competitively inhibit glucuronidation of lamotrigine. Evidence so far appears limited to this case report. In view of increased risk of rash with increased lamotrigine levels (see also Lamotrigine + Valproate interaction, below), it may be prudent to monitor combination. Further study is needed.

1. Kaufman KR,Gerner R. Lamotrigine toxicity secondary to sertraline. Seizure (1998) 7, 163–5.