Lamotrigine may be of use in treatment-resistant bipolar depression

An open-label medication augmentation trial for treatment-resistant bipolar depression found no significant differences between lamotrigine, inositol and risperidone, although the results of secondary analyses suggest lamotrigine may be the most effective.Sixty-six patients with bipolar disorder type I or II with a major depressive episode of at least eight weeks were recruited to the trial from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).Patients had not responded to treatment in the first 12 weeks of standard or randomised care pathways for bipolar depression or had failed to respond to at least two trials of antidepressants or an antidepressant and mood stabiliser regimen.Patients were randomly assigned to open-label adjunctive treatment with lamotrigine, risperidone or inositol for 16 weeks in addition to their current open-label mood stabiliser therapy with active antidepressant(s).Randomisation included assignment to one of three comparison groups: lamotrigine versus risperidone (n=17); lamotrigine versus inositol (n=31); or risperidone versus inositol (n=21).No significant differences in recovery (defined as no more than two symptoms meeting DSM-IV threshold criteria for a major depressive, manic or hypomanic episode, and no significant symptoms present for eight weeks) were observed for any of the paired comparisons. However, post-hoc secondary analyses showed a recovery rate of 23.8% for lamotrigine compared with rates of 17.4% and 4.6% for inositol and risperidone, respectively, although these differences were not significant. These secondary analyses also showed lamotrigine to be associated with greater improvements in depression symptoms, overall severity, and functioning at exit compared with inositol and risperidone.In addition, patients assigned to lamotrigine therapy stayed in the randomisation phase for longer than those assigned to inositol or risperidone.No differences in the rate of adverse events were observed for any of the paired comparisons. The researchers conclude that few patients with treatment-resistant bipolar depression would be expected to recover with the addition of risperidone, while adjunctive lamotrigine and inositol may have some potential.They add that further studies to evaluate other potential augmenting agents are needed.Reference...