Risk of neutropenia among clozapine users and non-users: results from 5,847 patients

Objective: Clozapine is underprescribed due to neutropenia risk. Blood tests every 3 months in those on continuous treatment for > 1 year who have never had an absolute neutrophil count (ANC) < 2,000/µL has been proposed as a monitoring strategy; however, there are no South American data to support this recommendation. This study sought to investigate whether clozapine use and other variables could explain the occurrence of ANC < 1,000/µL in patients with severe mental disorders. Methods: A total of 5,847 subjects were included, 1,038 on clozapine. We performed a Cox regression considering the outcome as ANC < 1,000/µL at any time point. Predictors were sex, age, ethnicity, clozapine use, ANC > 2,000/µL during the first year of blood monitoring, and presence of a severe medical condition. Results: In the Cox regression model, ethnicity (white) (hazard ratio [HR] 0.53; 95%CI 0.29-0.99, p < 0.05) and ANC > 2,000/µL (HR 0.04; 95%CI 0.01-0.10, p < 0.001) were protective factors, while presence of a severe medical condition (HR 69.35; 95%CI 37.45-128.44, p < 0.001) was a risk factor for ANC < 1,000/µL. Other variables were not significant, including clozapine use (HR 1.33; 95%CI 0.74-2.39, p > 0.05). Conclusions: These findings suggest that clozapine does not increase the risk of neutropenia in subjects with ANC > 2,000/µL during the first year of use and in the absence of a severe medical condition. These results could help guide clinical and public-health decisions regarding clozapine blood monitoring guidelines.

Proinflammatory and anti-inflammatory biomarkers in schizophrenia and influence of simvastatin on the interleukin-6.

The present study sought to assess biomarkers of inflammation in stable patients with schizophrenia (SZ) on clozapine therapy. We recruited 60 outpatients with SZ and 60 healthy controls, matched for sex and age. Compared with controls, patients had significantly increased concentrations of interleukin-6 and tumor necrosis factor-α. Interestingly, patients on simvastatin had lower interleukin-6 levels compared with patients not on simvastatin and controls. This study corroborated previous evidence for increased inflammatory biomarkers in SZ and detected a potential anti-inflammatory action of simvastatin in patients with a clinical diagnosis of SZ on clozapine therapy.

Resveratrol Supplementation Did Not Improve Cognition in Patients with Schizophrenia: Results from a Randomized Clinical Trial.

BACKGROUND: Schizophrenia (SZ) is associated with psychotic experiences and cognitive deficits. Therefore, cognitive function is one of the most critical determinants of quality of life in this pathology. Resveratrol has been related to neuroprotective action, but there are no studies evaluating resveratrol in SZ. The objective of this study was to determine the efficacy of resveratrol supplementation on cognition in individuals with SZ. METHODS: This is a 1-month randomized, double-blind, and controlled trial (NCT 02062190), in which 19 men with diagnosis of SZ, aged 18-65 years, were assigned to a resveratrol supplementation group (200 mg) or placebo group (200 mg), with a 1-month follow-up. Applying a series of cognitive tests assessed neuropsychology performance (Hopkins Verbal Learning Test, Stroop Color and Word Test, and Weschler Adult Intelligence Scale) and Brief Psychiatric Rating Scale assessed psychopathology severity. RESULTS: There were no significant improvement in neuropsychology performance (episodic memory, working memory, attention and concentration capacity, inhibitory control, interference measures, selective attention, and mental flexibility) and psychopathology severity after 1 month of resveratrol supplementation (P > 0.05). CONCLUSION: In conclusion, we have shown that 1 month of a resveratrol supplementation (200 mg/day) did not improve episodic memory, working memory, attention and concentration capacity, inhibitory control, interference measures, selective attention, and mental flexibility as compared with placebo in patients with SZ.