Background: Although clozapine is an effective option for treatment-resistant schizophrenia (TRS), there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine. The main purpose of this randomized, double-blind, placebo-controlled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of clozapine-resistant treatment-refractory schizophrenia (CTRS) patients. Methods: A total of 80 patients were recruited and randomly assigned to receive initial clozapine plus amisulpride (amisulpride group) or clozapine plus placebo (placebo group). Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Clinical Global Impression (CGI) scale scores, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Treatment Emergent Symptom Scale (TESS), laboratory measurements, and electrocardiograms (ECG) were performed at baseline, at week 6, and week 12. Results: Compared with the placebo group, amisulpride group had a lower PANSS total score, positive subscore, and general psychopathology subscore at week 6 and week 12 ( P _Bonferroni < 0.01). Furthermore, compared with the placebo group, the amisulpride group showed an improved RBANS language score at week 12 ( P _Bonferroni < 0.001). Amisulpride group had a higher treatment response rate ( P = 0.04), lower scores of CGI severity and CGI efficacy at week 6 and week 12 than placebo group ( P _Bonferroni < 0.05). There were no differences between the groups in body mass index (BMI), corrected QT (QTc) intervals, and laboratory measurements. This study demonstrates that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients. Conclusion: This study indicates that amisulpride augmentation therapy has important clinical significance for treating CTRS to improve clinical symptoms and cognitive function with tolerability and safety. Trial registration Clinicaltrials.gov identifier- NCT03652974. Registered August 31, 2018, https://clinicaltrials.gov/ct2/show/NCT03652974

Social cognitive and negative symptoms impairment may increase the risk of mental disability in individuals with schizophrenia. However, randomized controlled studies on the effectiveness of accelerated intermittent theta burst stimulation (iTBS) for social cognition and negative symptoms in individuals with schizophrenia are very limited. A total of 125 individuals with schizophrenia were recruited, 66 of whom were randomly divided into an active iTBS group (n=34) and sham iTBS group (n=32) by stratified sampling. Participants received either active iTBS or sham iTBS targeting the left dorsolateral prefrontal cortex (DLPFC) 20 sessions for 4 weeks under navigation. The Facial Emotion Recognition Test (FERT), Hinting Task (HT), and Positive and Negative Syndrome Scale (PANSS) were measured at baseline, 2 weeks, and 4 weeks. The trial protocol was registered with the Chinese Clinical Trial Registry (ChiCTR2100051984). Sixty patients (90.90%) completed the intervention and the 4-week follow-up, including 29 women (43.94%) and 37 men (56.06%) with a mean (SD) age of 47.53 (10.17) years. The primary outcomes showed FERT scores (week 2; 0.27 [95% CI, 0.09 to 0.45]; P< .01; ES 0.14) (week 4; 0.63 [95% CI, 0.45 to 0.80]; P< .001; ES 0.47) and HT scores (week 2; 1.00 [95% CI, -0.02 to 1.98]; P< .05; ES 0.67) (week 4; 2.13 [95% CI, 1.21 to 3.06]; P< .001; ES 0.27) in the active iTBS group were significantly different from those in the sham iTBS group at 2 and 4 weeks of follow-up. The secondary outcome showed that the negative symptom score (-3.43 [95% CI, -4.85 to -2.01]; P< .001; ES 0.29) of the active iTBS group was significantly different from that of the sham iTBS group at the 4th week of follow-up. Accelerated iTBS can effectively ameliorate the social cognition and negative symptoms of individuals with schizophrenia. These results suggest that accelerated iTBS may be a safe and effective neuromodulation technique to improve the overall functional recovery of individuals with schizophrenia, and has a good clinical application prospect.

Prior studies indicate that subjects undergoing methadone maintenance therapy (MMT) may experience anxiety, depression and cravings. This study aimed to explore the impact of intermittent theta burst stimulation (iTBS)-MMT combination on craving and emotional symptoms of opioid use disorder. This comparative study included subjects with opioid use disorder at the Methadone Maintenance Clinic of Pudong New Area between September 2019 and March 2020. The subjects were divided into two groups: those who received iTBS-MMT combination treatment (iTBS-MMT) and those who received MMT treatment and sham stimulation treatment (MMT). Outcomes were reduction rate of anxiety, depression and craving. Anxiety was measured by Hamilton Anxiety (HAMA) scale, depression was determined by Hamilton Depression (HAMD) scale and craving was analyzed using visual analog scale. A total of 76 subjects completed the treatment, with 38 subjects in each group. Twenty days after treatment, subjects in the iTBS-MMT group had significant improvement of anxiety (HAMA reduction rate), depression (HAMD reduction rate) and craving (Craving reduction rate) reduction rate compared with MMT group. iTBS-MMT combination treatment may produce better drug craving reduction and emotional improvement than MMT alone.