AbstractBackgroundSchizophrenia is a severe and chronic mental disorder affecting approximately 0.5%-1% of the global population. Patients often experience significant impairments or poor in social functioning, which leads to a diminished quality of life. Therefore, improving social functioning has become one of the important targets for intervention.Aims and ObjectivesThis prospective, multi-centre, single-arm clinical trial aimed to investigate the effects of blonanserin on social and neurocognitive functioning in patients with first-episode schizophrenia.MethodBlonanserin treatment (flexible oral dose ranging from 8 - 24 mg/d) was administered for 26 weeks. Outcome measures included the Personal and Social Performance (PSP) scale for evaluating social functioning, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) for measuring neurocognitive performance, and the Positive and Negative Syndrome Scale (PANSS) for assessing symptom severity. Incidence of adverse drug reactions (ADRs) were also recorded and analysed.ResultsA total of 96 patients with first-episode schizophrenia were recruited and proceeded to analysis. Following 26 weeks of blonanserin treatment, all outcome measurements demonstrated significant improvement during the follow-up period. Notably, PSP scores exhibited a continuous increase of 68.1% ± 103.73% (46.8±14.47 at baseline, 69.4±17.40 at week 26, p<0.001), indicating positive effects on social functioning that were already noticeable by week 8. Neurocognitive impairment evaluated by MCCB Global Deficit Score (GDS), showed significant improvement (1.6±1.1 at baseline, 1.3±0.9 at week-26, p=0.007). Moreover, PANSS scores consistently decreased, with an overall average reduction of 40.0% ± 18.41% (85.6±13.53 at baseline, 51.3±15.49 at week 26, p<0.001). Impressively, the minimal response to blonanserin treatment was evident as early as week 2. 245 cases of ADRs occurred in 79 (82.3%) patients in this study, with nervous system disorders being the most frequent ADRs (87 cases in 64 (66.7%) patients). Most ADRs relevant to blonanserin treatment were mild to moderate.Discussion & ConclusionBy intricately modulating both dopamine D2/3 and serotonin 5-HT2A receptor subtypes within the brain, blonanserin targets key elements that are widely recognized to play a crucial role in the pathophysiology of the disorder. In this study, blonanserin treatment exhibited favourable effects on social functioning, neurocognitive performance and symptom severity in individuals with first-episode schizophrenia. And it was also well tolerated. These compelling findings highlight the potential of blonanserin as a viable option for patients with schizophrenia encountering functional and neurocognitive impairment.