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The present 16-week double-blind, randomized, placebo-controlled trial had the aim to explore the efficacy of lamotrigine add-on pharmacotherapy on clinical symptomatology and cognitive functioning in a sample of patients with treatment-resistant obsessive-compulsive disorder (OCD) receiving serotonin reuptake inhibitors (SRIs). After clinical and neurocognitive assessments, patients were randomly allocated to receive, in a double-blind design, 100 mg/day of lamotrigine or a placebo. A final sample of 33 patients completed the study. The results obtained indicate that lamotrigine added to stable SRI treatment substantially improved obsessive-compulsive (Yale-Brown Obsessive Compulsive Scale: obsessions, p < 0.0001; compulsions, p < 0.0001; total score, p < 0.0001), and affective symptoms (Hamilton Rating Scale for Depression p < 0.0001). Regarding cognitive functions, improvement was observed only in Semantic Fluency (p = 0.004). The findings provide evidence that lamotrigine augmentation of SRI treatment is well tolerated and may be proposed as an effective therapeutic strategy to improve outcome in treatment-resistant OCD.
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