New Pharmacological Targets for the Treatment of Schizophrenia: A Literature Review.

Background The pharmacological treatment of schizophrenia is currently based on the employment of anti-psychotic medications showing an antagonism of dopaminergic and serotoninergic. 20-40% of patients are drug-resistant or residually symptomatic in the long-term anti-psychotic treatment, and new strategies are needed for improving their functional and cognitive impairment. Methods This systematic review summarized the evidence from the literature regarding the newer pharmacological targets proposed for the treatment of psychosis. We included 128 peer-reviewed articles and 5 other relevant sources published from 2002 to 2020 on PubMed EMBASE, The Cochrane Library, Google Scholar. Results It has extensively described the possible role of glutamate and its receptors as targets of the anti-psychotic mechanism of action. Glutamatergic neurotransmission and NMDA receptors hypofunction are involved in the neurobiological explanatory model of psychosis and possibly targeted for the successful treatment of cognitive and residual symptoms. The results show efficacy of D-cycloserine (antagonist at the Glycine site of the NMDA-R) in the treatment of negative symptoms of schizophrenia as well as Memantine (NMDA: Receptor antagonist) on cognition and psychopathology. The putative anti-psychotic effect of cannabidiol on positive symptoms and cognition will also be discussed, even if more evidence is required. The action on serotoninergic and GABAergic receptors will be considered a new pharmacological target, with a possible efficacy of Vabicaserin on symptoms of psychosis. Mynocicline has shown improvements in cognitive symptoms in schizophrenia as well as Erythropoietin. Oxytocin reported an antipsychotic-like effect and COX-2 inhibitors reported a reduction of positive symptoms of psychosis in the first episode of illness. Conclusion This narrative report suggests a promising role of new agents in the treatment of Schizophrenia, even if more research is needed to approve their clinical employment.