Undiagnosed metabolic syndrome and other adverse effects among clozapine users of Xhosa descent

Abstract

Background. Clozapine use is known to be associated with significant side-effects, including prolongation of the QT-interval, agranulocytosis and metabolic syndrome. However, few data exist on the prevalence of clozapine side-effects in patients of Xhosa descent. Objective. To gather data from Xhosa patients with schizophrenia to establish the prevalence of clozapine side-effects in this population. Methods. Twenty-nine Xhosa patients with schizophrenia (as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR))who had been receiving clozapine treatment for >1 year on an outpatient basis were selected for inclusion. All patients were participating in a genetics study in the Cape Metropolitan area. The participants were evaluated for the presence of side-effects (tests including an electrocardiogram, white blood cell count (WCC) and fasting blood glucose). Results. The prevalence of metabolic syndrome was 44.8% (95% confidence interval (CI) 26.7 -62.9) and of undiagnosed diabetes mellitus 13.8% (95% CI 1.24 -26.34). There was a significant association between metabolic syndrome and body mass index (BMI) (p<0.01). The mean (SD) WCC was 7.8 × 10 9 /L (2.8), with 3.4% of the subjects having a WCC <3.5 × 10 9 /L. Sedation (82.8%; 95% CI 69.0 -96.5), hypersalivation (79.3%; 95% CI 64.6 -94.1) and constipation (44.8%; 95% CI 26.7 -62.9) were common. The mean QT-interval was 373.8 (35.9) ms and 10% had a corrected QT-interval >440 ms. There was an association between the duration of clozapine treatment and QT-interval (with Bazett's correction). Conclusion. The high prevalence of metabolic syndrome and undiagnosed diabetes mellitus in this sample points to a need to monitor glucose levels and BMI on a regular basis. A larger study should be done to accurately quantify the differences in prevalence of side-effects between population groups. MethodsPatients with schizophrenia (as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)) of Xhosa descent being treated as outpatients and using clozapine as the primary treatment modality were selected from a large genetics study done in the Cape Metropolitan area.[12] Sixty (8.1%) of the 738 Xhosa participants with schizophrenia in the genetic study were taking clozapine at time of assessment. A convenience sample of 29 (48%) of the 60 participants was analysed for this study. Participation was voluntary. Informed written consent was obtained from all participants. The study was approved by the Health Research Ethics Committee of Stellenbosch University. The prerequisites for the study were that the subjects needed to be schizophrenia patients of Xhosa descent (defined as 4/4 grandparents reported as of Xhosa descent) who had been receiving clozapine for >1 year and be outpatients at time of assessment.Demographic, age, treatment duration and treatment dose data were collected by means of a structured questionnaire. A family history of cardiovascular disease (including hypertension) and a smoking history were obtained. Two self-reported q...

Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis

“…For our study, we extracted data from the Clozaril-alone arm of the crossover study [ 62 ], as the prevalence of constipation within both arms over the study was unclear and this arm provided more data. Additionally, eight prospective studies [ 17 , 49 , 58 , 61 , 65 , 66 , 67 , 68 ], six retrospective cohort studies [ 48 , 50 , 56 , 57 , 59 , 69 ], and four cross-sectional studies [ 24 , 70 , 71 , 72 ] were included. Of the 21 studies that reported on the prevalence rate of clozapine-associated constipation, one was carried out across more than one geographical region [ 63 ].…”

“…Of the 21 studies that reported on the prevalence rate of clozapine-associated constipation, one was carried out across more than one geographical region [ 63 ]. Five studies were carried out in Europe [ 24 , 57 , 63 , 68 , 70 ], seven in North America [ 17 , 45 , 50 , 59 , 60 , 63 , 64 , 65 , 72 ], six in Asia [ 49 , 56 , 58 , 61 , 63 , 66 ], two in Africa [ 62 , 71 ], one in the Middle East [ 48 ], and one in Oceania [ 69 ]. Nine studies were conducted in in-patient settings ( n = 395) [ 17 , 48 , 49 , 50 , 58 , 59 , 60 , 61 , 65 ], 10 involved outpatients ( n = 627) [ 24 , 56 , 57 , 62 , 66 , 68 , 69 , 70 , 71 , 72 ], and two included patients from mixed settings ( n = 56) [ 63 , 64 ].…”

“…Five of the studies assessed for constipation or adverse effects of clozapine as a primary outcome [ 24 , 57 , 59 , 70 , 71 ], while six other studies assessed for these as secondary outcome measures [ 17 , 49 , 56 , 60 , 68 , 71 ]. Six studies used self-reports from patients to measure for constipation [ 48 , 50 , 59 , 62 , 64 , 65 ], nine studies used a checklist to determine the presence or absence of constipation in participants [ 17 , 24 , 56 , 60 , 63 , 66 , 69 , 70 , 72 ], and four screened for constipation using structured clinical assessments [ 49 , 61 , 68 , 71 ]. One study identified constipation using laxative prescription rates in patients [ 57 ], with only one other study reporting on laxative use [ 71 ].…”

Metabolic Syndrome in South African Patients with Severe Mental Illness: Prevalence and Associated Risk Factors

“…Data for South Africa are limited to three studies [ 15 – 17 ]. A study of 84 long term in patients that included patients with cognitive and personality disorders reported a MetS prevalence of 32% [ 15 ] while the other two reported on the prevalence of MetS in patients taking a single antipsychotic [ 16 , 17 ]. From population studies in South Africa, the reported prevalence of MetS is 22.1% in rural [ 18 ] and 31.7% in urban black South African communities [ 19 ].…”

Prevalência De Síndrome Metabólica Em Pacientes Com Esquizofrenia Refratária

“…O índice de massa corporal (IMC) é, indiscutivelmente, o indicador antropomé-trico mais utilizado mundialmente, sendo extremamente útil na prática clínica para determinar a obesidade. Esse índice pode ser utilizado como uma medida de rastreamento de SM em pacientes que possuem esquizofrenia refratária e utilizam clozapina (28,30). Estudo que comparou as alterações metabó-licas possivelmente relacionadas ao uso de antipsicóticos mostrou que 52,3% dos indivíduos estavam com sobrepeso e indicou que aqueles que possuíam esquizofrenia refratá-ria apresentaram as maiores taxas (31).…”