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.
In a rat model of schizophrenia-like symptoms induced by ketamine, the natural compound mangiferin (from mango) reduced behavioral abnormalities, oxidative stress, inflammation, and glial activation in brain regions involved in motor and cognitive function. Ketamine caused reduced exploratory activity, hyperlocomotion, anxiety, elevated dopamine, and disrupted antioxidant defenses. Mangiferin at 50–75 mg/kg restored locomotor activity, antioxidant enzymes, and reduced inflammatory markers and astrocytosis, while increasing Nrf2, a key antioxidant regulator. The antipsychotic risperidone improved behavior and inflammation but was less effective at normalizing redox markers. The findings suggest mangiferin may be a candidate for adjunctive therapy targeting redox–glial dysfunction in schizophrenia.