Improvement in Depressive Symptoms With Felbamate: A Case Report

Sir: Prevalences of psychiatric illness are significantly higher in patients with seizure disorder, essentially with temporal lobe and refractory epilepsy, with depression occurring in up to 30%.¹ Felbamate is an antiepileptic drug used as both monotherapy and adjunctive therapy in patients with partial seizures with or without secondary generalization. There are sparse data concerning the effects of felbamate in psychiatric disorders. To our knowledge, this is the first case reporting antidepressant effects of felbamate.

Case report

Ms. A is a 29-year-old woman who has intractable seizures. When she was 16 years old, she had Epstein-Barr virus encephalitis and was in a coma for about 3 weeks. She has had seizures since then with a frequency of once per week, has undergone extensive workup by neurologists on several occasions, and has been diagnosed with both grand mal and petit mal seizures. The duration of her grand mal seizures range from 10 to 15 minutes. There is no history of head trauma or febrile seizures. Magnetic resonance imaging of her head revealed bilateral mesial temporal lobe sclerosis. Her recent electroencephalogram showed a generalized slowing maximal in the posterior regions with broadly contoured slow spike and wave discharges with less frequent temporal epileptiform discharges. Over the course of her seizures, she has tried several antiepileptic medications in different combinations with minimal benefits; these include carbamazepine, topiramate, oxcarbazepine, lamotrigine, divalproex sodium, phenobarbital, zonisamide, primidone, leve-tiracetam, pregabalin, clonazepam, phenytoin, gabapentin, and felbamate. Other options are being explored, such as vagal nerve stimulation and epilepsy surgery.

She has a family psychiatric history of depression in her mother. There is no substance use history. In 2007, the patient reported an interesting finding of a significant improvement in her mood with felbamate. Over the course of her illness, she has been on treatment with felbamate on 3 different occasions and has observed that her mood is good when she is taking felbamate. She has also noticed an improvement in energy levels and describes that she is less tearful and has an overall sense of well-being whenever she is on treatment with felbamate. Her most recent dose of felbamate was 600 mg 3 times a day, and the neurologists were planning to discontinue this due to the concerns of adverse effects. This patient was worried about having a relapse of depression when her felbamate was discontinued. We offered her a trial of sertraline, and she was willing to try.

Disruption of glutamate neurotransmission has been linked to major depression, and drugs targeting N-methyl-D-aspartate (NMDA) receptors have shown antidepressant properties.² Some animal studies have shown that many antidepressants have activity on the NMDA receptors. One of the proposed mechanisms of action of fluoxetine is by suppressing glutamate release.³ Felbamate indirectly antagonizes NMDA receptors.

A better control of seizures leads to symptomatic improvement in comorbid depression. In our patient, felbamate was not very effective in improving her seizures, but symptomatic improvement in her depression was evident with its use. It has been suggested that a better psychiatric outcome in patients with seizure disorder could be achieved by treating baseline “anergic” profiles (apathy, depression, fatigue) with activating antiglutamatergic drugs such as lamotrigine and felbamate.⁴ However, felbamate's adverse effect profile, with black box warnings of risks such as aplastic anemia and fatal hepatitis, may limit its use. Additional research with controlled studies is warranted to substantiate our finding of an antidepressant effect of felbamate.