‎ lamotrigine augmentation versus placebo in serotonin ‎reuptake inhibitors-‎resistant obsessive-compulsive disorder: ‎a randomized controlled trial

objective: serotonin reuptake inhibitors are frequently used in first-line treatments for patients ‎with obsessive-compulsive disorder. nevertheless, many of these patients do not ‎respond well to initial therapy. the hypothesis of glutamatergic dysfunction in specific ‎brain regions has been proposed in the pathophysiology of obsessive-compulsive ‎disorder. this study was designed to evaluate the possible efficacy of lamotrigine, a ‎glutamatergic agent in serotonin reuptake inhibitors-resistant patients with obsessive-‎compulsive disorder.‎ method: this study was a 12-week, double blind, randomized, placebo-controlled trial of ‎adjunctive fixed-doses of lamotrigine (100 mg) to serotonin reuptake inhibitors therapy ‎in obsessive-compulsive disorder. eligible subjects who had a total y-bocs of 21 or ‎above were randomly assigned to receive adjunctive treatment with either lamotrigine ‎‎(n = 26), or placebo (n = 27). response to lamotrigine was defined as clinical ‎improvement (>25% decrease in the total y-bocs score), which was administered at ‎weeks 0, 8 and 12.‎ results: at the endpoint (week 12), significant differences were observed in obsession, ‎compulsion, and total y-bocs scores comparing lamotrigine to placebo (p = 0.01, ‎‎0.005 and 0.007 respectively). the mean reduction in obsession, compulsion and total ‎scores in lamotrigine group was about 4.15, 4.50 and 8.73, respectively. similarly, the ‎mean reductions in the placebo group were 2.52, 2.56 and 5.07. effect sizes for efficacy ‎measures were calculated by cohen’s d, and it was calculated as 0.54 for the total ‎ybocs.‎ conclusion : our findings provide evidence that this augmentation is well tolerated and may be an ‎effective strategy for patients with refractory obsessive-compulsive disorder.‎‎