Lamotrigine augmentation for the treatment-resistant mood disorder

Abstract

Purpose: A number of depressed patients do not respond adequately to standard antidepressant treatments, and some of them subsequently suffer from treatment-resistant mood disorder (TRMD). Lamotrigine (LTG) is the only mood stabilizer that is effective for preventing depressive episodes of bipolar disorders. This study aimed to evaluate the efficacy of LTG augmentation in Japanese patients with TRMD. Methods: The subjects were 30 patients with refractory depression who had already shown insufficient response to multiple pharmacotherapy including antidepressants, mood stabilizers and atypical antipsychotics. The diagnoses were major depressive disorder (n=16), bipolar disorder (n=10) and dysthymic disorder (n=4). All patients gave written informed consent to receive LTG as an off-label indication in Japan after explanation for possible risks of unwanted skin reactions. The daily dose of LTG was titrated by the clinician's decision (88.0±61.9 mg/day). Treatment response was assessed by Montgomery-Asberg Depression Rating Scale (MADRS) and Global Assessments of Functioning (GAF) before and after the 8-week LTG augmentation. Results: Significant improvements were observed in the scores of MADRS (25.3±10.1 → 14.7±10.5) and GAF (49.2±12.3 → 64.1±11.7) after the 8-week LTG augmentation (p=0.0010). Greater number of the past mood episodes and shorter duration of the present depressive episode are associated with better response to LTG. Mild adverse skin reactions developed in 10 patients although 8 out of them were treatment responders. Discussion: LTG augmentation may be effective for the treatment of TRMD, especially with shorter duration of unremitted depression and more recurrent episodes. However, attention should be paid to the development of adverse skin reactions in LTG responders.