Obsessive-compulsive disorder (OCD) is a psychiatric syndrome characterized by unwanted and repetitive thoughts and repeated ritualistic compulsions aimed to decrease the distress. Symptoms can cause severe distress and functional impairment. OCD affects 2-3% of the population and is ranked within the ten leading neuropsychiatric causes of disability. Dysfunction of the cortico-striatal-thalamo-cortical circuitry (CSTC) has been implicated in OCD, including altered brain activation and connectivity. A complex dysregulation of glutamatergic signaling within the cortico-striatal circuitry has been proposed in OCD. Data obtained by several studies are suggesting of a reduced glutamatergic concentrations in the anterior cingulate cortex, combined with overactivity of glutamatergic signaling in the striatum and orbitofrontal cortex. A growing number of RCTs have assessed the utility of different glutamate-modulating drugs as an augmentation or monotherapy in OCD, including refractory patients. However, there are relevant variations in between studies in terms of treatment-resistance, comorbidity, age and gender of the patients. At the present time four RCTs are available on the efficacy of memantine as an augmentation medication for refractory OCD patients.
Investigators intend to conduce a double-blind, randomized, parallel group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine, a low-to-moderate affinity noncompetitive NMDAR antagonist that is currently approved for the treatment of Alzheimer disease, as an augmentative agent to a SSRI in treatment of patients affected by severe refractory OCD. Study design consists of four distinct periods (52 weeks) including memantine titration, neuropsychological assessment and follow-up.
