Occurring in up to 80% of patients with
epilepsy, depression in
epilepsy may manifest as (i)
major depressive disorder, meeting Diagnostic and Statistical Manual, 4th edition (DSM-IV) diagnostic criteria; (ii) atypical depression or
dysthymia; or (iii) a dysthymic-like disorder with intermittent symptoms that can be milder than those of major depression. Depressive symptoms impair patients' health-related quality of life and may affect the
clinical course of
epilepsy. Depressive symptoms in
epilepsy have been attributed to several causes, including endocrine and/or metabolic effects of
seizures; the psychological response to
epilepsy and its associated mental, physical and social challenges; common pathogenic mechanisms between depression and
epilepsy; and the adverse effects of certain
antiepileptic drugs (AEDs), particularly
GABAergic agents, such as
vigabatrin,
tiagabine,
topiramate and
phenobarbital. Whereas some AEDs impair mood, others appear to improve aspects of mood or are mood neutral. Demonstrable
antidepressant efficacy of AEDs used to manage
seizures could have a significant impact on the care of patients with
epilepsy. The AED
lamotrigine has been demonstrated to be effective in the treatment of depressive symptoms in patients with
epilepsy. In randomized, double-blind, clinical trials in patients with
epilepsy, depressive symptoms improved more with
lamotrigine monotherapy than
valproate monotherapy and more with
lamotrigine adjunctive
therapy than placebo. Results of open-label studies of
lamotrigine monotherapy and adjunctive
therapy are consistent with the results of double-blind clinical trials.
Lamotrigine-associated improvement in depressive symptoms is independent of its
anticonvulsant efficacy. In prospective assessments,
gabapentin,
levetiracetam and
oxcarbazepine each exhibited potentially beneficial effects on depressive symptoms in patients with
epilepsy. However, evidence for the efficacy of
gabapentin,
levetiracetam and
oxcarbazepine in the treatment of depressive symptoms in
epilepsy is inconclusive at present because the effects of each agent have only been reported in single studies of an open-label design and with small sample sizes.