Abstract

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.