Lamotrigine Augmentation of Serotonin Reuptake Inhibitors in Severe and Long-Term Treatment-Resistant Obsessive-Compulsive Disorder

The treatment recommendations in obsessive-compulsive disorder (OCD) after lack of response to selective serotonin reuptake inhibitors (SSRIs) include augmentation with other drugs, particularly clomipramine, a more potent serotonin reuptake inhibitor (SRI), or antipsychotics. We present two cases of response to lamotrigine augmentation in treatment-refractory OCD; each received multiple SRI trials over a >10-year period. The first patient had eleven years of treatment with multiple combinations including clomipramine and SSRIs. She had a >50% decrease of Y-BOCS (from 29 to 14) by augmenting paroxetine (60？mg/day) with lamotrigine (100？mg/day). The second patient had 22 years of treatment with multiple combinations, including combinations of SSRIs with clomipramine and risperidone. She had an almost 50% decrease of Y-BOCS (from 30 to 16) and disappearance of tics by augmenting clomipramine (225？mg/d) with lamotrigine (200？mg/day). These two patients were characterized by lack of response to multiple treatments, making a placebo response to lamotrigine augmentation unlikely. Prospective randomized trials in treatment-resistant OCD patients who do not respond to combinations of SSRIs with clomipramine and/or antipsychotics are needed, including augmentation with lamotrigine. Until these trials are available, our cases suggest that clinicians may consider lamotrigine augmentation in such treatment-resistant OCD patients. 1. Introduction There is general agreement in the obsessive-compulsive disorder (OCD) literature that the first line for pharmacological treatment is the selective serotonin reuptake inhibitors (SSRIs). This is supported by practical guidelines [1], meta-analysis [2], and treatment algorithms [3]. The recommendations after lack of response to SSRIs are not so well established but usually include augmentation with other drugs: (1) particularly clomipramine, a more potent serotonin reuptake inhibitor (SRI), or (2) antipsychotics [1–6]. More recently, augmentation with glutamatergic agents has also been recommended [3]. Lamotrigine is an antiepileptic drug and mood stabilizer that has antiglutamatergic properties [7] and has been occasionally used in OCD treatment. Two small open studies used lamotrigine for treating obsessive symptoms, one in schizophrenia [8] and another in bipolar disorder [9]. A small open study [10] of augmentation of SRIs with 100？mg/day of lamotrigine in 8 patients reported negative results. A case report [11] of lamotrigine augmentation using up to 150？mg/day in a patient with a stable dose of clomipramine