In this investigation, the effects of
lamotrigine versus placebo on depressive symptoms in patients with
epilepsy were prospectively assessed. This investigation was a secondary analysis of a randomized, double-blind, placebo-controlled, parallel-group study in which adult patients received adjunctive
lamotrigine (n=32) or placebo (n=38) for a 7-week dose escalation phase, followed by a 12-week maintenance phase, for primary generalized tonic-clonic (PGTC)
seizures. Mood symptoms were assessed with the Beck Depression Inventory, second edition (BDI-II), the Profile of Mood States (POMS), and the Cornell
Dysthymia Rating Scale-Self-Report (CDRS). Mean (SD) BDI-II scores at screening reflected mild depressive symptoms and were similar between groups (
lamotrigine 18.3 (12.1), placebo 16.8 (12.0)). At the end of the maintenance phase, mean (SD) improvement from baseline was greater with
lamotrigine than placebo with respect to BDI-II score (
lamotrigine 8.9 (7.6), placebo 1.7 (8.5), P=0.01) and POMS total score (
lamotrigine 32.0 (30.4), placebo 6.5 (32.3), P=0.03) and numerically greater with
lamotrigine than placebo for CDRS score (
lamotrigine 7.3 (7.8), placebo 4.1 (13.9), P=0.50). Among the subset of patients with at least mild depression (BDI-II score10), mean improvement from baseline was numerically, but not statistically significantly, greater with
lamotrigine (11.5, n=13) than placebo (3.1, n=18) (P=0.054). Median percentage reductions in seizure frequency were significantly greater with
lamotrigine than placebo during the escalation phase, the maintenance phase, and the escalation and maintenance phases combined for PGTC
seizures and all
generalized seizures. However, improvement in seizure frequency was not correlated with improvement in mood (r=0.1, P=ns). Compared with placebo,
lamotrigine improved mood symptoms independently of seizure reduction in patients with
generalized seizures.
Lamotrigine may be useful in treating patients with
epilepsy and comorbid depressive symptoms.