Clinical Drug Investigation

, Volume 16, Issue 2, pp 125–133 | Cite as

Clinical Experience with Lamotrigine Monotherapy in Adults with Newly Diagnosed Epilepsy

A Review of Published Randomised Clinical Trials
  • E. Lynette Mullens
Clinical Review


Objectives: This paper aimed to provide an overview from published randomised clinical trials of the efficacy and tolerability of lamotrigine monotherapy compared with carbamazepine and phenytoin when initiated in adult patients with newly diagnosed epilepsy.

Design: The review included two double-blind, randomised trials of lamotrigine monotherapy compared with carbamazepine and phenytoin, respectively, and one open randomised trial comparing lamotrigine with carbamazepine. The results of the three trials were pooled for comparison of tolerability.

Setting: Multicentre in Europe.

Patients: Adult patients (>12 years of age) with newly diagnosed partial seizures (with or without secondary generalisation) and primary generalised tonic-clonic seizures (n = 443 patients on lamotrigine, n = 246 on carbamazepine, n = 95 on phenytoin).

Results: Comparable efficacy was demonstrated between lamotrigine and both carbamazepine or phenytoin. The time to withdrawal survival analysis supported a significant difference in favour of lamotrigine [hazard ratio 1.57 (95% CI 1.07 to 2.31)] in the double-blind trial. Overall, twice the proportion of patients withdrew from carbamazepine or phenytoin because of adverse events (19.1 and 18.9%, respectively) compared with lamotrigine (9.5%). Lamotrigine was particularly well tolerated with regard to adverse effects affecting the central nervous system. Rash was the most common adverse event necessitating discontinuation of each drug, the rates being very similar across treatment groups (6.1% on lamotrigine, 8.9% on carbamazepine, 5.3% on phenytoin). The rate of rash resulting in withdrawal of lamotrigine was clearly related to the dose escalation employed in the different trials during the first month of therapy.

Conclusions: Lamotrigine is an effective monotherapy treatment for adult patients with newly diagnosed epilepsy, and is better tolerated than either carbamazepine or phenytoin monotherapy. The incidence of rash requiring withdrawal of lamotrigine is related to dose escalation (2.2% of patients withdrawing when the recommended escalation was followed).


Adis International Limited Carbamazepine Lamotrigine Dose Escalation Partial Seizure 
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Copyright information

© Adis International Limited 1998

Authors and Affiliations

  • E. Lynette Mullens
    • 1
  1. 1.Glaxo Wellcome Research and DevelopmentGreenford, MiddlesexEngland

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