JMIR Publications

ABSTRACT

Background:

Background:

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.

Objective:

The main purpose of this study is 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’s disease, as an augmentative agent to a SSRI in treatment of moderate to severe OCD. The second aim of the study is to evaluate the effect of memantine on patients without cognitive impariment an improvement of cognitive funtions. The third aim is to investigated if response to memantine could be modulate by variables such as gender, symptoms subtypes and duration of untrated illness.

Methods:

Methods:

Investigators intend to conduce a double-blind, randomized, parallel group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine 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.

Results:

Results:

Trough the slow-titration and follow-up we will observe the minimum effective dose of memantine and its residual efficacy after drug withdrawal during follow-up procedure. In addition, measuring the potential executive function impairments during the study period we might exlude or confirm if memory and/or attention are modulators of the overall clinical improvement.

Conclusions:

Conclusions:

The innovation of this research proposal is not limited to evaluation of the efficacy and safety of memantine as augumentation medication in OCD. We would test if memantine acts as a pure anti-obsessive medication or if memantine improving concentration and attention abilities mimics an anti-obsessive effect. Clinical Trial: ClinicalTrials.gov: NCT05015595 (MemaROCD), Registred on 20 August 2021.