Coronary Artery Disease in Patients with Severe Mental Illness.

Severe mental illnesses (SMI), such as schizophrenia and bipolar disorder, are associated with a decrease in life expectancy of up to two decades compared with the general population, with cardiovascular disease as the leading cause of death. SMI is associated with increased cardiovascular risk profile and early onset of incident cardiovascular disease. Following an acute coronary syndrome, patients with SMI have a worse prognosis, but are less likely to receive invasive treatment. In this narrative review, the management of coronary artery disease in patients with SMI is discussed, and avenues for future research are highlighted.

Outcome of a psychosocial health promotion intervention aimed at improving physical health and reducing alcohol use in patients with schizophrenia and psychotic disorders (MINT).

BACKGROUND: Life expectancy is reduced by 19 years in men and 17 in women with psychosis in Sweden, largely due to cardiovascular disease. AIM: Assess whether a psychosocial health promotion intervention improves cardiometabolic risk factors, quality of life, and severity of illness in patients with psychotic disorders more than treatment as usual. METHODS: A pragmatic intervention trial testing a manual-based multi-component health promotion intervention targeting patients with psychosis. The Swedish intervention was adapted from IMPaCT therapy, a health-promotion program based on motivational interviewing and cognitive behavioral therapy, designed to be incorporated into routine care. The intervention group consisted of 119 patients and the control group of 570 patients from specialized psychosis departments. Outcome variables were assessed 6 months before intervention during the run-in period, again at the start of intervention, and 12 months after the intervention began. The control group received treatment as usual. RESULTS: The intervention had no significant effect on any of the outcome variables. However, BMI, waist circumference, systolic BP, heart rate, HbA1c, general health, and Clinical Global Impressions Scale score improved significantly during the run-in period before the start of the active intervention (observer effect). The multi-component design meant that treatment effects could only be calculated for the intervention as a whole. CONCLUSION: The results of the intervention are similar to those of the U.K. IMPaCT study, in which the modular health-promotion intervention had little effect on cardiovascular risk indicators. However, in the current study, the run-in period had a positive effect on cardiometabolic risk factors.

The Use of Granulocyte Colony-Stimulating Factor in Clozapine Rechallenge: A Systematic Review.

PURPOSE/BACKGROUND: Clozapine is associated with hematological abnormalities, with neutropenia and agranulocytosis of most concern. Granulocyte colony-stimulating factor (G-CSF) has been used to support clozapine rechallenge after neutropenia with the aim of maintaining the neutrophil count. This study aims to explore the practice, use, safety, and efficacy of G-CSF in this context. METHODS/PROCEDURES: We conducted a systematic review to identify all studies investigating or describing G-CSF as a prophylaxis to enable continued clozapine treatment during a rechallenge. FINDINGS/RESULTS: We identified 32 reports of patients who received G-CSF either regularly (n = 23) or as required (n = 9) to support clozapine rechallenge after an episode of neutropenia necessitating discontinuation of clozapine. Seventy-five percent (n = 24) of published cases remained on clozapine with the use of continual prophylactic G-CSF or after single G-CSF administrations (n = 8). Seventy percent (n = 16) of patients in receipt of continual prophylactic G-CSF were successfully maintained on clozapine. However, 1 of the 3 episodes of rechallenge in those with a history of severe agranulocytosis (absolute neutrophil count <0.1 × 10/L) had a recurrence of agranulocytosis at week 9. IMPLICATIONS/CONCLUSIONS: Our findings suggest that G-CSF can sometimes be safely used to support the maintenance of normal neutrophil counts and clozapine use after neutropenia. Publication bias is an important limitation, however. Also, few reports clearly documented the presence or absence of an independent nonclozapine cause of the index neutropenia, which may have increased success rates. Furthermore, adverse events were not systematically recorded. Prospective studies are needed to determine safety because if agranulocytosis occurs on clozapine while supported by G-CSF, there is no obvious alternate rescue therapy to promote granulopoiesis. From the available data, it is not possible to recommend this course of action for someone with a true clozapine agranulocytosis.

Clozapine-Associated Agranulocytosis Treatment With Granulocyte Colony-Stimulating Factor/Granulocyte-Macrophage Colony-Stimulating Factor: A Systematic Review.

PURPOSE/BACKGROUND: Clozapine is associated with hematological abnormalities, notably neutropenia, which may progress to agranulocytosis. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used to reduce the frequency and duration of clozapine-associated neutropenia. This review aims to explore the use, efficacy, and tolerability of these cytokines in the treatment of clozapine-associated agranulocytosis. METHODS/PROCEDURES: We conducted a systematic review of published interventional and observational studies, case series, and case reports where G-CSF/GM-CSF was used to treat clozapine-associated agranulocytosis. FINDINGS/RESULTS: We identified 29 reports (40 patients). The median duration of neutrophil recovery time after stopping clozapine and starting cytokine treatment was 7 days (range, 2-13 days) for those with agranulocytosis (absolute neutrophil count < 0.5 × 10 cells/L). Ninety-four percent (n = 29) had no serious adverse reactions, and no deaths occurred. IMPLICATIONS/CONCLUSIONS: Our findings indicate that G-CSF/GM-CSF use is well tolerated and suggest that G-CSF can sometimes be safely used to reduce the duration of neutropenia associated with clozapine use. However, the interpretation of this outcome is difficult, given the likely publication bias for positive outcomes in case reports.

Correlation between human leukocyte antigen class II alleles and HAI titers detected post-influenza vaccination.

Influenza is a major cause of morbidity and mortality. Despite vaccination, many elderly recipients do not develop a protective antibody response. To determine whether Human Leukocyte Antigen (HLA) alleles modulate seroprotection to influenza, a cohort of HLA class II-typed high-risk vaccine recipients was investigated. Haemagglutinin inhibition (HAI) titres were measured 14-40 days post-subunit vaccination. Seroprotection was defined as HAI titres reaching 40 or greater for all three vaccine strains. HLA-DRB1*04∶01 and HLA-DPB1*04∶01 alleles were detected at higher frequencies in seroprotected compared with non-seroprotected individuals. Thus, the presence of certain HLA class II alleles may determine the magnitude of antibody responses to influenza vaccination.

The relationship between prolactin levels and glucose homeostasis in antipsychotic-treated schizophrenic patients.

OBJECTIVES: To determine if prolactin levels are associated with glucose-insulin homeostasis in antipsychotic-treated patients with schizophrenia. METHOD: Prolactin levels and glucose homeostasis (quantified using oral glucose tolerance testing, insulin measurement, and homeostasis model assessment) were measured in 15 patients with elevated prolactin levels secondary to antipsychotic treatment of schizophrenia (mean age, 30.4 years; SD, 5.3 years). The effect of reducing prolactin levels by switching patients' antipsychotic treatment to clozapine was ascertained by performing the measures before and after the switch to clozapine. RESULTS: There was no significant correlation between prolactin and glucose-insulin measures at baseline. There was a large reduction in prolactin (593 mIU/L) after switching to clozapine, but this was not associated with changes in glucose-insulin measures. CONCLUSIONS: Prolactin is not a significant determinant of glucose-insulin homeostasis in patients taking antipsychotics for schizophrenia. There was no benefit from lowering prolactin levels using clozapine. This could be because prolactin does not have a major effect on glucose homeostasis or that the effects of prolactin reduction are countered by clozapine.

The effect of clozapine on factors controlling glucose homeostasis.

BACKGROUND: This prospective study examines the effect of clozapine on factors determining glucose homeostasis. METHOD: The sample consisted of all patients meeting DSM-IV criteria for schizophrenia who commenced clozapine treatment within the South London and Maudsley hospitals during 1 year (2000-2001). Growth hormone (GH), insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) were measured in 19 patients (10 female; mean age = 31.1 years [SD = 5.8]; 9 black British/African, 10 white British) before and after a mean of 2.5 (SD = 0.9) months of clozapine treatment. RESULTS: Baseline IGFBP-1 was low. IGFBP-1, GH, and IGF-1 were not significantly changed by clozapine treatment. CONCLUSIONS: Clozapine does not alter GH, IGF-1, or IGFBP-1 within 3 months of commencing treatment, indicating that alteration in glucose tolerance associated with clozapine treatment involves other mechanisms yet to be elucidated. Baseline abnormalities in IGFBP-1 indicate a preexisting susceptibility to glucoregulatory dysfunction.

A prospective study of impairment in glucose control caused by clozapine without changes in insulin resistance.

OBJECTIVE: This prospective study examines the effect of clozapine on glucose control and insulin sensitivity. METHOD: Glucose homeostasis was measured in nine female and 11 male patients with schizophrenia (mean age=30.5 years, SD=7.4) before clozapine treatment and after a mean of 2.5 months (SD=0.95) of clozapine treatment. Oral glucose tolerance and insulin levels were measured. Insulin resistance level was measured by the homeostasis model assessment. RESULTS: Eleven (55%) of the patients developed abnormal glucose control; the mean age of these patients was 30.2 (SD=7.1), and five were women. Patients' insulin resistance at baseline (mean insulin resistance level=3.88, SD=2.93) was unaffected by clozapine. Mean fasting and 2-hour glucose levels significantly increased by 0.55 mmol/liter and 1.4 mmol/liter, respectively. There was no correlation between change in body mass index and change in fasting glucose levels. CONCLUSIONS: Clozapine impairs glucose control within 4 months of treatment, independent of changes in insulin sensitivity and body mass index.