Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder

Giacomo Grassi, Chiara Cecchelli, Luisa Vignozzi, Silvia Pacini Neuroscience Department, Brain Center Firenze, Florence, ItalyCorrespondence: Giacomo GrassiBrain Center Firenze, Viale Belfiore 36, Florence 50144, ItalyEmail giacomograssimd@gmail.comAbstract: Treatment-resistance is a frequent condition for obsessive-compulsive disorder (OCD). Over the past decades, a lot of effort has been made to address this issue, and several augmentation strategies of serotonergic drugs have been investigated. Antidopaminergic drugs are considered the first choice as augmentation strategy for treatment-resistant OCD patients, but they seem to work only for a subset of patients, and none of them have been officially approved for OCD. Recently, the role of glutamate and inflammation in OCD pathophysiology clearly emerged, and this has led to several investigations on glutamatergic and anti-inflammatory agents. Results seem promising but still inconclusive. Probiotic interventions (considered to modulate the immune systems and the brain activity) are gaining attention in several psychiatric fields but are still at their early stages in the OCD field. Research on new treatment approaches for OCD is moving forward, and more than one hundred interventional trials are ongoing around the world. While the vast majority of these trials involve neuromodulation and psychotherapeutic approaches, only a small proportion (around 20%) involve the investigation of new pharmacological approaches (tolcapone, nabilone, psilocybin, troriluzole, nitrous oxide, rituximab, naproxen, and immunoglobulins). Here, we provide a comprehensive review of investigational and experimental drugs to treat OCD.Keywords: OCD, glutamate, immune system, inflammation, probiotics, pharmacotherap