259. A RAPID CLINICAL RESPONSE TO ETIFOXINE IN TREATMENT-RESISTANT OBSESSIVE-COMPULSIVE DISORDER: A CASE REPORT AND LITERATURE REVIEW

Abstract Background Obsessive-compulsive disorder (OCD) is significantly influenced by neurosteroidogenesis, which is mediated by the translocator protein 18 kDa (TSPO), a transmembrane protein located primarily in mitochondria.1 Despite numerous studies in the treatment of mood, anxiety, and stress-related disorders2,3, the TSPO ligands’ role in the treatment of OCD is yet to be elucidated. Aims & Objectives To describe the short-term use of etifoxine, a TSPO ligand, in a patient with treatment-resistant OCD and to discuss the possible mechanisms of a rapid clinical response. Method A case of treatment-resistant OCD who had a dramatic response to etifoxine was described, and a comprehensive literature search was conducted. Results A 36-year-old man was diagnosed with OCD since the age of 14. He had received numerous psychotropics, including maximum dosages of SSRIs (escitalopram, sertraline), SNRIs (venlafaxine), and TCAs (clomipramine, imipramine), and several previous augmentations (lithium, risperidone, aripiprazole, quetiapine), but failed to respond. He refused to receive psychotherapy, electroconvulsive therapy, and transcranial magnetic stimulation. Finally, he received neurosurgery twice at the ages of 30 (bilateral anterior cingulotomy) and 32 years old (subcaudate tractotomy). The responses were initially good, but then the OCD relapsed after 1.5 years and 6 months, respectively. His symptoms never remit. As the disease progressed, he became depressed and unable to work. His latest regimen included venlafaxine 375 mg/d, clomipramine 150 mg/d, aripiprazole 15 mg/d, and clonazepam 4 mg/d. The patient gradually developed suicidal ideation within a month but refused hospitalization because of contamination fear. However, he agreed to try etifoxine 150 mg/d along with the same ongoing medications. After one day of etifoxine use, his OC symptoms reduced dramatically, and the suicidal idea disappeared. He could sleep and join his family activity. Unfortunately, he developed an itchy skin rash and limb edema on Day 3. Despite this, he continued etifoxine, as it dramatically helped ameliorate his OC symptoms. On day 6, he came to the hospital for a psychiatric follow-up. At this point, the etifoxine was discontinued, resulting in resolution of the rash and limb edema, and all drug adverse reactions completely resolved within 2 weeks. The patient remained clinically stable after the etifoxine was discontinued and could be followed up in the outpatient setting. Discussion & Conclusions This is the first report of the use of a TSPO ligand in OCD treatment. This case illustrates the potential therapeutic option of etifoxine for treatment-resistant OCD. There are at least 2 possible mechanisms of the rapid response to etifoxine: (1) Increase endogenous neurosteroidogenesis. A TSPO-PET study in OCD patients has demonstrated increased TSPO expression in the dorsal caudate, orbitofrontal cortex, thalamus, ventral striatum, and dorsal putamen 1 and suggests a link of neurosteroid and OCD pathology. Etifoxine could increase endogenous neurosteroidogenesis, resulting in less anxiety. 4 (2) Gut-brain axis. Microbiome dysbiosis is linked with OCD pathology.5 A study in healthy human demonstrated that a five-day treatment with etifoxine reduced the number of some bacterial species. 6 TSPO can be a novel target for future research in OCD treatment.