ABSTRACT
INTRODUCTION: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but it is markedly underutilized, particularly in the US Black population, partly because of concern over clozapine-associated low absolute neutrophil count (ANC). People of African descent have a lower normative ANC range than the White population, which is associated with a specific "ACKR1-null" ("Duffy null") CC genotype (SNP rs2814778) on the ACKR1 gene, termed benign ethnic neutropenia (BEN). The range of ANC variability and safety of clozapine have not been established in people with BEN or examined prospectively in people of African descent. METHODS: We completed a multisite, 6-month, prospective, open-label clinical trial of clozapine treatment in people of African descent with schizophrenia spectrum disorders for whom clozapine was clinically indicated, with or without the ACKR1-null genotype. We examined clozapine safety and weekly ANC during clozapine treatment and evaluated ANC variability by ACKR1-null genotype, sex, study site, and clozapine dosing using repeated measures analysis of covariance. Genotype was assayed using TaqMan® technology. RESULTS: We enrolled 274 participants, of whom 227 (82.8 %) completed 6 months of clozapine treatment. There was one case of severe neutropenia (<500 cells/mm3) (0.36 %) over 1467.6 person-months of clozapine exposure. This participant recovered without sequelae after discontinuation of clozapine. Of the 249 participants with known genotypes, 199 (79.9 %) had the ACKR1-null genotype. Neutropenia (<1500 cells/mm3) occurred significantly more often in the ACKR1-null group (33 % [65/199]) than in those with the T allele (6 % (3/50); p < 0.001). Fourteen (5 %) patients discontinued due to adverse events. Rates of infection and fever were low and sialorrhea was the commonest side effect (N = 187, 68 %). CONCLUSION: To our knowledge, this is the largest prospective clozapine trial in people of African descent. Severe neutropenia was rare, despite the high prevalence (80 %) of the ACKR1-null genotype. Our findings suggest that clozapine can be used safely in Black patients including those with BEN.
ABSTRACT
Schizophrenia is a severe mental disorder with various medical comorbidities and early mortality. Hyperprolactinemia is common in women and its impact on sexual function, galactorrhea and amenorrhea is well known. This paper evaluates the risk of 25-hydroxy vitamin D deficiency and other metabolic related laboratory abnormalities in women with schizophrenia having hyperprolactinemia (N = 43). The mean prolactin level in these women was 88.5 ± 56.0 ng/mL. We found that 100% of women were overweight of which 74% (32/43) of the women were obese, 56% (23/41) had abnormal total cholesterol levels and 30% (13/43) had high fasting blood glucose. Vitamin D levels were considered deficient or inadequate in 37% of women. We did not see significant correlations of prolactin with laboratory measures, however all female patients had elevated and high prolactin levels, leading to low variability in a small sample, which may have precluded seeing any direct relationships. Recognizing prolactin related side effects and understanding the role of other health measures seen in women with antipsychotic induced hyperprolactinemia in our female patients are critical steps toward better personalization of their care and recovery.
