RESUMEN
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.
RESUMEN
Background: There is a growing global concern about the public health implications of the increasing population of the elderly. One main issue of concern is centered on how to address their mental health needs using homegrown interventions and services. We expect that important lessons on geriatric mental health issues would be brought to fore in this report. Methods: This is a four-year (2007-2011) retrospective report on the mental health services rendered to 938 clients aged 60 years and above at a Lagos based mental health treatment facility in Nigeria. Designed questionnaires were filled with socio-demographic and clinical data obtained from patients case notes based on the objectives of the study. Results: The mean (standard deviation) age of elders was (±7.93) 69.6 years, and 65.5% were females. Majority were married, self-employed and belonged to low socio-economic status (73.1%, 63.1% and 63.2%, respectively). Close to two-thirds (62.4%) commute for at least one hour to get treatment. The commonest diagnosis was psychotic disorders (34.8%), while 5.5% had Alzheimer's dementia. Some 96.5% of the elders were solely on medications. About a quarter had past history of mental illness and 48.5% reported co-morbid medical conditions, with cardiovascular problems (53.0%) being the commonest physical comorbidity. The middle old along with very old elders (aged≥70 years), and those with at least tertiary education, were more likely to present with dementia were more likely to present with index episode of mental illness and receive outpatient care Conclusion: The elders were managed for a wide range of treatable mental illnesses and other comorbidities and commute for hours to access care. Pharmacotherapy was the preponderant sole treatment modality. There is need for sustained development of expertise to enhance multimodal care and scaling up of comprehensive geriatric mental health services. Further research is needed on how to appropriately link and/or integrate geriatric care with services at all-tiers of health care delivery.
