Background: The present study aimed to systematically evaluate three prolactin-sparing antipsychotics for treating schizophrenia. Methods: We performed a meta-analysis of three prolactin-sparing antipsychotics in patients with schizophrenia. Endpoints of interest were the Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions-Severity (CGI-S) and acceptability (all cause discontinuation). Results: A total of 12 trials (2,723 patients) and three drugs (aripiprazole, quetiapine, and ziprasidone) were included. On the PANSS scale, aripiprazole (mean difference [MD]: -6.98, 95% CrI: -12.35, -1.38) was statistically more effective than placebo. When assessed by BPRS, aripiprazole (MD: -9.01, 95% CrI: -15.81, -3.12), quetiapine (MD: -7.13, 95% CrI: -9.78, -4.29) and ziprasidone (MD: -4.97, 95% CrI: 9.96, -0.21) had greater efficacy, when compared to placebo. Regarding CGI-S, quetiapine (MD: -0.55, 95% CrI: -0.82, -0.25) was significantly superior to placebo. In terms of acceptability, aripiprazole (OR: 0.54, 95% CrI: 0.41, 0.73), quetiapine (OR: 0.49, 95% CrI: 0.36, 0.68) and ziprasidone (OR: 0.68, 95% CrI: 0.48, 0.96) were more acceptable than placebo. The benefit risk analysis revealed that quetiapine has the best efficacy and acceptability profile among the three prolactin-sparing antipsychotics. Conclusions: Quetiapine may offer an optimal benefit-risk balance when a prolactin-sparing antipsychotic is indicated.
BACKGROUND: To investigate the effects of adjunct ketamine treatment on depressive symptoms and brain activity in chronic treatment-resistant schizophrenia (CTRS) patients with treatment-resistant depressive (TRD) symptoms. METHODS: Calgary Depression Scale for Schizophrenia (CDSS), positive and negative syndrome scale (PANSS), and regional homogeneity (ReHo) results were compared before versus after ketamine treatment in 12 CTRS patients with TRD symptoms. RESULTS: From 7 days to 14 days after the first ketamine administration, CDSS and PANSS total scores were reduced by 63.8% and 12.9%, respectively. By day 21, ReHo values had increased in the main components of the default mode network (DMN) and bilateral orbitofrontal cortex (OFC) after family-wise error correction. ReHo alterations did not correlate with TRD symptom changes. TRD symptoms relapsed by the 21-day time point, while increased ReHo was sustained. No adverse secondary effects (ASEs) necessitating medical intervention occurred. CONCLUSIONS: Adjunct ketamine alleviation of TRD symptoms lasted only a week, whereas increased ReHo in DMN regions and the OFC in CTRS patients was maintained beyond 2 weeks, indicating that adjunct ketamine is not well-suited for CTRS patients with TRD symptoms and that effects on functional activity dissociate from effects on TRD symptoms. This small-sample pilot study provides clues for further research into therapy for TRD symptoms in CTRS patients.