Are we moving forward from amisulpride? LB-102 ( N- methyl amisulpride) in acute schizophrenia

Schizophrenia has a low prevalence but a high health burden. Although used in schizophrenia, amisulpride has limited blood-brain barrier penetration. LB-102 (N-methylated amisulpride) maintains the ability to antagonize D2- and 5-HT7-receptors with longer receptor occupancies than amisulpride. A phase 2 clinical trial (NOVA) has showed that LB-102 has some efficacy in acute schizophrenia, but this comes with adverse events, such as increased prolactin levels, that need further investigation. The inpatient setting of NOVA may have contributed to the improvement observed with LB-102. Based on NOVA, LB Pharmaceutics have moved LB-102 into phase 3 for the treatment of acute exacerbations of schizophrenia. Like NOVA, the participants of NOVA2 will be inpatients. Consequently, this trial will not address the issue of whether LB-102 is effective in the outpatient setting, and these needs testing. A recently approved new approach to treating schizophrenia is the bitopic M1/M4 muscarinic receptor agonist xanomeline. When xanomeline was compared to amisulpride, it ranked lower. In conclusion, further clinical trials are needed to determine whether LB-102 is better than amisulpride and xanomeline in the treatment of schizophrenia in both inpatients and outpatients.