Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder

Treatment-resistant obsessive-compulsive disorder (OCD) is common, and while antidopaminergic drugs are the first-choice augmentation strategy for serotonergic medications, they benefit only a subset of patients and lack official approval for OCD. Emerging evidence implicates glutamate and inflammation in OCD, prompting investigation of glutamatergic and anti-inflammatory agents, though results remain inconclusive. Probiotic interventions, which modulate the immune system and brain activity, are gaining attention but are still early in OCD research. Over one hundred interventional trials are ongoing worldwide, mostly involving neuromodulation and psychotherapy; only about 20% test new pharmacological approaches such as tolcapone, nabilone, psilocybin, troriluzole, nitrous oxide, rituximab, naproxen, and immunoglobulins. This review comprehensively examines investigational and experimental drugs for OCD.

Study at a glance

Abstract

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.