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Background: Two distinct subtypes of treatment-resistant schizophrenia (TRS) have been recently reported, including early-treatment resistance (E-TR) as the dominant subtype and late-treatment resistance (L-TR). However, the response rate to clozapine, incidence of clozapine-induced prediabetes/diabetes, and effects of metformin at preventing clozapine-induced prediabetes/diabetes in patients with schizophrenia E-TR subtype need investigating. To assess clozapine-induced metformin-resistant prediabetes/diabetes and its correlation with clinical efficacy in schizophrenia E-TR subtype. Methods: This prospective cohort study enrolled 230 patients with schizophrenia E-TR subtype from Tianjin Kangtai Hospital between January 2015 and December 2020.The patients were treated with adequate doses of clozapine for 16 weeks, during which patients with prediabetes/diabetes were assigned to receive add-on metformin. Incidence of clozapine-induced prediabetes/diabetes and metformin-resistant prediabetes/diabetes and the efficacy of clozapine as assessed by the Positive and Negative Syndrome Scale (PANSS) score. Findings: Clozapine-induced prediabetes/diabetes occurred in 176 patients (170 prediabetes and 6 diabetes), with 76.52% incidence. The blood sugar of 43 (24.43%) patients was controlled with metformin. Despite add-on metformin, 47.06% (74/170) of patients with clozapine-induced prediabetes progressed to diabetes. In total, the incidence of clozapine-induced metformin-resistant prediabetes/diabetes was 75.57% (133/176). On completion of 16-week clozapine treatment, 16.52% (38/230) patients showed clinical improvement with PANSS scores of ≥50% declining. Furthermore, clozapine-induced prediabetes/diabetes was significantly correlated with the poor clinical efficacy of clozapine for schizophrenia E-TR subtype. In comparison with patients that did not have clozapine-induced prediabetes/diabetes, clinical efficacy was significantly lower in patients with clozapine-induced prediabetes/diabetes. Of note, the lowest clinical efficacy detected in patients with clozapine-induced diabetes [odds ratio (OR) of 0.18; 95% confidence interval (CI), 0.07–0.44]. Interpretation: The incidence of clozapine-induced metformin-resistant prediabetes/diabetes was considerably high in the schizophrenia E-TR subtype. Clozapine-induced metformin-resistant prediabetes/diabetes represents an independent risk factor that adversely affects the clinical efficacy of clozapine for the schizophrenia E-TR subtype. This study provided new evidence for re-evaluating the use of clozapine for TRS, especially E-TR subtype, and the use of metformin for the glycemic control of clozapine-induced prediabetes/diabetes. Funding: This study was supported by the National Natural Science Foundation of China (81871052 and 81571319). Declaration of Interests: All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and there is no conflict of interest to disclose. Ethics Approval Statement: The study protocol was reviewed and approved by the Ethic Committee of Tianjin Kangtai Hospital (Tianjin, China).

Background Effective secondary prevention is essential for reducing stroke recurrence. Objective This parallel randomized-controlled study aimed to evaluate the impact of a pharmaceutical care program on risk factor control (blood pressure, blood glucose, lipid profile, and medication adherence) and hospital readmissions in post-stroke care. Setting The First Hospital of Hebei Medical University, China. Method Ischemic stroke patients were enrolled in the study. Upon hospital discharge, patients were randomly allocated either to a control group (CG, no pharmaceutical care) or to an intervention group (IG, monthly pharmaceutical care follow-up for 6 months). The interventions aimed to increase medication adherence and improve risk factor control through education and counseling. Medication adherence and surrogate laboratory markers of risk factors were assessed and compared between the two groups. Main outcome measures Blood pressure, blood glucose, lipid profile, and medication adherence. Results A total of 184 patients with ischemic strokes were randomly assigned, and 84 patients in IG and 82 in CG were analyzed. There were no significant differences (P > 0.05) in both groups concerning demographic and clinical characteristics. Compared to CG, at the 6-month follow-up, medication adherence rates significantly increased regarding antihypertensive drugs (92.86% versus 78.57%, P = 0.031), anti-diabetic drugs (91.67% versus 69.7%, P = 0.02), and lipid-lowering drugs (77.38% versus 60.98%, P = 0.022) in IG. Compared to CG, more patients in IG attained the goal surrogate risk factor control markers of hemoglobin A1c (87.88% vs. 52.78%, P = 0.038) and low-density lipoprotein-C (66.67% vs. 48.78%, P = 0.02). Significantly fewer patients were re-admitted to the hospital in IG than CG (7.14% vs. 18.3%, P = 0.03). Conclusion Pharmaceutical care programs can improve risk factor control for the secondary prevention of stroke recurrence in ischemic stroke patients.

Schizophrenic patients often experience visual hallucinations (VHs) and auditory hallucinations (AHs); however, brain aberrations associated with combined VH and AH in schizophrenic patients remains poorly documented. Changes to the brain and cognition during the first episode of untreated schizophrenic patients (FUSCH) with both VHs and AHs (FUSCHVA) were evaluated. One-hundred and fifty-seven patients were enrolled that had FUSCH (1) with VHs but not AHs (FUSCHV), and (2) with AHs but not VHs (FUSCHA), plus FUSCHVA and healthy controls (n = 30). Gray matter volume (GMV) and MATRICS Consensus Cognitive Battery (MCCB) was measured to reflect impairments to the brain and cognition, respectively. FUSCHVA patients had the severest cognitive impairment for all components of the MCCB, followed by FUSCHV and FUSCHA patients. Compared to healthy patients, FUSCHVA patients had reduced GMV in the occipital, parietal, frontal, and temporal cortex, and increased GMV in the hippocampus and striatum. Compared to FUSCHV patients, FUSCHVA patients had reduced GMV in the occipital cortex and postcentral gyrus, and increased GMV in the posterio-parietal lobe. Compared to patients with FUSCHA, the GMV in patients with FUSCHVV was reduced in the occipital cortex and posterio parietal lobe. In conclusion, visual and auditory hallucinations appear to deteriorate reciprocally in FUSCHVA patients, accompanied with sever cognitive impairments. Compared to AHs, VHs might be accompanied with severe GMV impairment in the brain, especially in the primary visual cortex and higher perception integration cortex (posterio parietal lobe) in patients with FUSCH.

This study aimed to investigate the safety and efficacy of high-dose vitamin B6 (vB6) as an adjunct treatment for antipsychotic-induced hyperprolactinemia (AIHP) in male patients with treatment-resistant schizophrenia (TRS). In this randomized double-blinded controlled study, patients were randomized (1:1) into a control group given aripiprazole (ARI; 10 mg/day; n = 100) or an intervention group given vB6 (300 mg/12 h for 16 weeks; n = 100). Prolactin levels, psychotic symptoms [Positive and Negative Syndrome Scale (PANSS)], cognitive function [MATRICS Consensus Cognitive Battery (MCCB)], liver function, kidney function, growth hormone level, micronutrient levels, blood lipids, and adverse secondary effects (ASEs)[Treatment Emergent Symptom Scale (TESS) and Barnes-Akathisia scale] were monitored. After a 16-week treatment period, the vB6 group showed a 68.1% reduction in serum prolactin levels (from 95.52 ± 6.30 μg/L to 30.43 ± 18.65 μg/L) while the ARI group showed only a 37.4% reduction (from 89.07 ± 3.59 μg/L to 55.78 ± 7.39 μg/L). During weeks 1–4, both treatments reduced prolactin similarly. Subsequently, the ARI effect plateaued, while the vB6 effect remained robust. The vB6 group showed better alleviation of psychotic symptoms and cognitive impairment. No serious ASEs were observed; ASEs were more frequent in the ARI group. AIHP reduction efficacy of vB6 was associated with baseline prolactin and triglyceride levels, total vB6 dosage, and education level. In conclusion, compared with the ARI group, TRS patients given vB6 showed better attenuation of AIHP, lower ASE scores, and greater improvements in clinical symptoms and cognitive impairments. These results support further consideration of vB6 as a putative treatment for AIHP.Trial Registration: ChiCTR1800014755