Lamotrigine (LTG) is a broad-spectrum antiepileptic drug with efficacy against both partial and generalized seizures. Many consider LTG to be an important alternative treatment for refractory generalized epilepsies in epilepsy patients with developmental disabilities (DD).

In a double-blind, placebo-controlled trial of LTG in treating the Lennox-Gastaut syndrome,88 33% of patients receiving LTG experienced a reduction in seizure frequency of at least 50%. This study noted minimal behavioral effects.

Two subsequent series found significant effects, both positive and negative, among DD epilepsy patients treated with LTG:

  • Beran and Gibson89 noted the development of aggressive or violent behavior (or both) in 14 of 19 patients who received LTG. One patient demonstrated behavioral improvement.
  • Ettinger et al.90 cited 3 of 20 mentally retarded epilepsy patients receiving LTG who developed new or worsened hyperactivity, irritability, and stereotypy. Conversely, another four patients exhibited positive psychotropic effects, including reduction in irritability and hyperactivity, decreased lethargy, diminished perseverative speech, or improvement in cooperation and better social engagement. Although behavioral improvements may have represented a mood-stabilizing effect of LTG in some, with increased alerting leading to irritability in others, the reasons for these disparate effects was unclear. Serum LTG levels did not predict who developed positive versus negative symptoms.

Anecdotal experience in epilepsy patients suggests that LTG may enhance alertness.

LTG now is being used for treatment-resistant bipolar disorder.91–93 Although more published double-blind trials address the use of carbamazepine and valproic acid, LTG (as well as gabapentin) appears to have a more favorable side effect profile, making it a better choice for mood stabilization in bipolar disorder.

A positive psychotropic effect of LTG is supported by the observation that several epilepsy patients who were entered in a randomized double-blind study of LTG and experienced only slight reductions in seizure severity still elected to remain in the drug trial and demonstrated elevated mood on quality-of-life measures.94 Meador and Baker95 also have shown LTG to possess favorable behavioral and cognitive effects.

DD patients receiving LTG should be observed for the development of allergic reactions, including pruritus and rash, which can progress to potentially life-threatening Stevens- Johnson syndrome.96

Adapted from: Ettinger AB, Barr WB, and Solomon SP. Psychotropic properties of antiepileptic drugs in patients with developmental disabilities. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;219–230. With permission from Elsevier (

Authored By: 
Sanford P. Solomon MD
William B. Barr MD
Alan B. Ettinger MD
Reviewed By: 
Steven C. Schachter MD
Wednesday, March 31, 2004