Oxcarbazepine improves mood in patients with epilepsy

Abstract

This study prospectively examined whether continued add-on treatment with oxcarbazepine (OXC) is associated with quantitative improvement in mood and anxiety symptoms in adult patients with partial epilepsy. Depressive symptoms and anxiety were assessed by clinical interview using the Hamilton Depression Rating Scale (HDRS), the Cornell Dysthymia Rating Scale (CDRS), the Beck Depression Inventory (BDI), and the Hamilton Anxiety Rating Scale (HARS). Forty controls (patients with epilepsy treated with antiepileptic drugs other than OXC) and 40 OXC-treated patients were enrolled and completed the study. In our study, a significant improvement in affect, as measured by the CDRS, was demonstrated during the course of OXC treatment for 3 months. HDRS and BDI scores also declined in the OXC-treated group, but these decreases did not reach statistical significance. In addition, 28 of 40 OXC-treated subjects who were dysthymic by CDRS criteria on study entry (score ⩾20) demonstrated affective improvement consistent with a treatment-related antidepressant effect (score <20). Although our results do not provide conclusive evidence supporting the specific use of OXC as an antidepressant, the significant decline in dysthymic symptoms in OXC-treated subjects compared with controls lends support to the hypothesis that OXC improves mood.

Introduction

Oxcarbazepine (OXC) is a keto-analog of carbamazepine and was developed to provide a compound chemically similar enough to carbamazepine to mimic its efficacy while improving its side effect profile. The effect of OXC is probably due to the blockade of voltage-sensitive sodium and calcium channels. OXC has been demonstrated to be effective in the treatment of partial seizures and painful neuropathies. The main active metabolite of OXC is the monohydroxy derivative (MHD). In contrast to carbamazepine and its active epoxide metabolite, OXC and its MHD have fewer side effects and negative drug interactions, so OXC has been further studied as a possible mood stabilizer, with the added advantage that fewer serious side effects are expected than with carbamazepine [1].

OXC has been approved as an anticonvulsant in Europe since the early 1980s; it was approved in the United States in 2000 for use as monotherapy in partial seizures in adults, and as an adjunctive therapy for partial and secondarily generalized seizures in children aged 4–16 [2].

There are few data on the teratogenicity of OXC, but it passes through the placenta and is eliminated in the maternal milk. Compared with carbamazepine, OXC is a much weaker inducer of cytochrome P450 3A4/5, and it inhibits only the 2C19 enzyme [3]. For this reason, there are few clinically significant drug interactions, although the plasma levels of the estrogen and progesterone components of oral contraceptives tend to be reduced. High-dose contraceptives, or alternative means of contraception, should be used to counteract this effect.

The most common side effects are headache, somnolence, dizziness, fatigue, and nausea. Other less common side effects are skin eruption, vomiting, parkinsonism, and leukopenia.

Hyponatremia, which is defined as a serum sodium level <125 mmol/L, has been reported in 25–50% of patients receiving OXC [4]. In addition, OXC may induce P450C1 and P450C24, the enzymes responsible for the metabolism of 25-hydroxyvitamin D [5]. Elevations in biomarkers that are consistent with increased bone turnover may well predispose patients to bone loss over time. It is possible that OXC has adverse effects on bone metabolism at higher doses, but not at lower doses, and surely more studies are needed to verify these findings. Anyway, it may be prudent for patients taking OXC to be prescribed 25-hydroxyvitamin D replacement.