Chris Bushe

Mortality in schizophrenia: a measurable clinical endpoint

Over the last five years, large data sets on mortality in schizophrenia have been published which have established mortality as a measurable clinical endpoint. Four issues need clarification: whether mortality rates are declining, what the causes of death are, the effects antipsychotic treatments have on mortality and whether these data inform as to how mortality may be reduced in the future. A PubMed search was carried out to identify relevant publications. The search strategy was conducted as a review focusing predominantly on data since 2006. A large number of retrospective epidemiological and prospective studies have been published on mortality rates and causation in schizophrenia, predominantly from 2006—2009. Data suggest that the mortality gap with the general population increased from the 1970s but may have peaked in the mid-1990s. The main causes of mortality are suicide, cancer and cardiovascular disease, with evidence that cancer mortality rates are similar to cardiovascular mortality rates. Mortality causation is dependent upon age of the cohort, length of follow up and type of study. Antipsychotic treatments reduce mortality when compared with no treatment and atypical antipsychotics do not appear to increase cardiovascular mortality and morbidity compared with conventionals; further research is required for any definitive conclusion.

A review of the association between antipsychotic use and hyperprolactinaemia

Recent evidence linking hyperprolactinaemia to longer-term clinical sequelae, including osteoporosis, hip fractures and possibly breast cancer, is increasing clinical awareness of the relevance of hyperprolactinaemia. A review of the literature finds clinical trials reporting some degree of comparative prolactin data among antipsychotics. Many of the randomised clinical trials (RCTs) do not report categorical rates of hyperprolactinaemia in contrast with the naturalistic studies, making it complex for clinicians to evaluate the extent and severity of hyperprolactinaemia. Hyperprolactinaemia is one of the commonest adverse events reported in clinical trials and can be found in association with all antipsychotics. The highest rates of hyperprolactinaemia are reported in association with risperidone and amisulpride, often as high as 80—90% of all female subjects and consistently greater than with the typical antipsychotics. Significant rates of hyperprolactinaemia of lesser severity and more transience have also been reported in association with other atypical antipsychotics.

Diabetes and schizophrenia 2005: are we any closer to understanding the link?

The association between schizophrenia and diabetes has been recognized for well over a century, but the underlying reasons for this association are unclear. In October 2003, an international group of diabetologists and psychiatrists met to review the literature relating to the association, and to create pragmatic guidelines for the management of diabetic risk in patients with severe mental illness. Since that meeting, over 100 additional papers have been published on the association between glucose abnormalities and schizophrenia, and this is a clear reflection of the level of interest in this clinically important area. Diabetes is highly prevalent among the schizophrenia population, but most sufferers remain undiagnosed in the community. The reasons why individuals with schizophrenia are more prone to developing diabetes than the general population are poorly defined, but likely to be multifactorial. The role of antipsychotic medications in the development of diabetes and other pre-diabetic states remains controversial, but it appears that the attributable risk is low. Traditional risk factors most probably account for much of the diabetes seen in schizophrenia populations, suggesting that routine screening and aggressive risk factor management are especially important in this patient group.

Long-term maintenance of weight loss in patients with severe mental illness through a behavioural treatment programme in the UK

Objective:  Obesity is common among people with severe mental illness (SMI). We report our experience from the first 4 years of The Cromwell House weight management clinic.

Prevalence of hyperprolactinaemia in a naturalistic cohort of schizophrenia and bipolar outpatients during treatment with typical and atypical antipsychotics

Hyperprolactinaemia is a common finding in patients treated with antipsychotics. A complete cohort of 194 schizophrenia and bipolar disorder patients receiving antipsychotics in a single community mental health trust in Halifax UK underwent routine prolactin screening in the absence of any reLevant symptomatoLogy. Values above the upper limit of normal were measured in 38% of the cohort and were more common in females (52%) than males (26%). Significantly elevated levels (>1000 mIU/l) were measured in 21% of the cohort. Risperidone monotherapy treatment was associated with hyperprolactinaemia in 69% of patients ( n = 35) and in 100% of female patients (n = 16) and amisulpride monotherapy in 100% (n = 7). Prolactin screening is not currently undertaken routinely in the UK. These data give some indication of prevalence of varying degrees of hyperproLactinaemia that might be found when screening an asymptomatic cohort of schizophrenia and bipolar outpatients. Clinicians may be helped by the reporting of such categorical data from clinical trials in addition to mean cohort values of prolactin. Long-term hyperprolactinaemia may be associated with clinical sequeLae in some patients.

Schizophrenia and breast cancer incidence: a systematic review of clinical studies.

OBJECTIVES Studies examining the incidence of breast cancer in schizophrenia patients report increased, reduced or similar incidence compared to the general population. We undertook a systematic review of published data to investigate possible reasons for the variable findings. METHODS The review was conducted according to the recommendations of the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) group [Stroup, D.F., Berlin, J.A., Morton, S.C., Olkin, I., Williamson, G.D., Rennie, D., Moher, D., Becker, B.J., Sipe, T.A., Thacker, S.B. 2000. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA. 283(15) 2008-2012.]. Methodological issues (Quality Markers) that may explain the variability in the data were identified. Data relating to these issues and the standard incidence rates were extracted. Results were then interpreted in relation to these quality markers. RESULTS Data are available from over 6000 female patients with schizophrenia from 13 studies and are reported in comparison to age matched general populations from the relevant country from 1986 to 2008. Although results are widely discrepant ranging from 52% increase in risk to 40% decrease, these data may be understood in terms of cohort age, size and length of follow up as the confounders. Six of 13 studies report an increased or marginally increased incidence of breast cancer. These tend to be studies with more than 100 incident cases of breast cancer, greater than 100,000 person years follow up and older populations. CONCLUSIONS Breast cancer may be increased in female subjects with schizophrenia. Inconsistencies in study findings may be due to methodological issues such as low statistical power and the age range of cohorts studied. There is no proven risk factor to explain these data; however reduced parity and hyperprolactinaemia may represent putative aetiological factors. Consideration of screening of female patients with schizophrenia for breast cancer is important for clinicians and researchers.

A well-being programme in severe mental illness. Baseline findings in a UK cohort

Introduction:  Patients with severe mental illness (SMI) have higher rates of cardiovascular disease (CVD) morbidity and mortality than the general population. In the UK, data were limited regarding the known prevalence of physical health screening of SMI patients.

The role of lifestyle interventions and weight management in schizophrenia.

The recognition that schizophrenia is associated with metabolic comorbidity and a subsequent greater risk of cardiovascular events compared to the general population has led to attempts to reduce this metabolic burden. Increased weight, and smoking rates combined with less exercise and poor dietary choices, have led to a variety of behavioural programmes and pharmacological agents being evaluated with the aim of improving lifestyle and managing weight. Adjunctive pharmacological strategies for weight management have not been shown to be consistently effective and remain contraindicated in many schizophrenia subjects. However some novel compounds with recent promising data suggest that research should not be abandoned. In contrast a variety of behavioural interventions have shown a consistent degree of success not only with weight management but also in achieving lifestyle changes. Many reported data-sets are naturalistic or open-label indicating that there is a difficulty in performing traditional randomized controlled studies in this area. The long-term naturalistic studies and holistic approaches show that weight management and significant lifestyle changes are attainable goals in schizophrenia patients. Weight management and lifestyle advice should be routinely offered to all schizophrenia subjects.

Cancer and schizophrenia: is there a paradox?

People with schizophrenia are more likely to die prematurely than the general population from both suicide and physical ill health. Published studies examining the incidence of cancer in schizophrenia patients report increased, reduced or similar incidence compared with the general population. Older studies tended to report lower incidence rates which fuelled speculation as to the biological and other mechanisms for this protective effect. Furthermore, mortality rates in patients with schizophrenia appear higher than expected. We undertook a non-systematic review of published data to give an overview for these variable findings and illustrate methodological confounders by highlighting a systematic review of breast cancer studies.

Systematic review of atomoxetine data in childhood and adolescent attention-deficit hyperactivity disorder 2009–2011: Focus on clinical efficacy and safety

Background: Clinicians obtain critical prescribing knowledge from clinical papers and review articles. This is the first published systematic review of clinical atomoxetine data covering 2009–2011. Objective: We aim to update clinicians on current clinical atomoxetine data with specific reference to time of onset of efficacy and maximal efficacy. These data may allow critical analysis of comparative efficacy between atomoxetine and stimulant medications. Methods: A formal systematic review of atomoxetine data from January 2009–June 2011 was conducted. The search term used was “atomoxetine” in the English language. The search yielded 747 citations from which 106 are clinical data. This paper includes clinical efficacy and safety data and excludes quality-of-life and review papers. Results: Atomoxetine has an onset of action within 4 weeks (possibly within 1 week in subsequent responders) but requires at least 12 weeks for full response to be demonstrated. Treatment-naïve cohorts (6–12 weeks) report effect sizes of 0.6–1.3. Using minimum 6-week clinical trial criteria, atomoxetine may demonstrate similar efficacy to methylphenidate comparing reduction in core ADHD symptoms in meta-analysis, although the diversity of the data makes interpretation complex. From epidemiological databases, cardiovascular and suicide-related events were similar to those seen in patients taking methylphenidate. Conclusions: Incremental response time to atomoxetine should be considered in the design of future comparative efficacy trials.