Smith M, Hopkins D, Peveler RC, Holt RI, Woodward M, Ismail K. First- v. second-generation antipsychotics and risk for diabetes in schizophrenia: systematic review and meta-analysis. Br J Psychiatry 192: 406-411

Department of Psychological Medicine, Institute of Psychiatry, King's College London, London SE5 9RJ, UK.
The British Journal of Psychiatry (Impact Factor: 7.99). 07/2008; 192(6):406-11. DOI: 10.1192/bjp.bp.107.037184
Source: PubMed


The increased prevalence of diabetes in schizophrenia is partly attributed to antipsychotic treatment, in particular second-generation antipsychotics, but the evidence has not been systematically reviewed.
Systematic review and meta-analysis comparing diabetes risk for different antipsychotics in people with schizophrenia.
We searched MEDLINE, PsycINFO, EMBASE, International Pharmaceutical Abstracts, CINAHL and Web of Knowledge until September 2006. Studies were eligible for inclusion if the design was cross-sectional, case-control, cohort or a controlled trial in individuals with schizophrenia or related psychotic disorders, where second-generation antipsychotics (defined as clozapine, olanzapine, risperidone and quetiapine) were compared with first-generation antipsychotics and diabetes was an outcome. Data were pooled using random effects inverse variance weighted meta-analysis.
Of the studies that met the inclusion criteria (n=14), 11 had sufficient data to include in the meta-analysis. Four of these were retrospective cohort studies. The relative risk of diabetes in patients with schizophrenia prescribed one of the second-generation v. first-generation antipsychotics was 1.32 (95% CI 1.15-1.51). There were insufficient data to include aripiprazole, ziprasidone and amisulpride in this analysis.
There is tentative evidence that the second-generation antipsychotics included in this study are associated with a small increased risk for diabetes compared with first-generation antipsychotics in people with schizophrenia. Methodological limitations were found in most studies, leading to heterogeneity and difficulty interpreting data. Regardless of type of antipsychotic, screening for diabetes in all people with schizophrenia should be routine.

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    • "times higher risk for diagnosed type 2 diabetes than those without schizophrenia (Cohen and De Hert, 2011). The elevated risk for type 2 diabetes in people with psychosis is therefore unlikely to be just a side effect of antipsychotic medication (Ramaswamy et al., 2006; Smith et al., 2008), and a variety of historical data and small proof of principle studies support the Danish population registry findings. The recent focus on diabetes "
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    ABSTRACT: The co-occurrence of type 2 diabetes and psychosis is an important form of medical comorbidity within individuals, but no large-scale study has evaluated comorbidity within families. The aim of this study was to determine whether there is evidence for familial comorbidity between type 2 diabetes and psychosis. Data were analysed from an observational study of a nationally representative sample of 1642 people with psychosis who were in contact with psychiatric services at the time of survey (The 2010 Australian National Survey of Psychosis). Participants were aged 18-64 years and met World Health Organization's International Classification of Diseases, 10th Revision diagnostic criteria for a psychotic disorder (857 with schizophrenia, 319 with bipolar disorder with psychotic features, 293 with schizoaffective disorder, 81 with depressive psychosis and 92 with delusional disorder or other non-organic psychoses). Logistic regression was used to estimate the association between a family history of diabetes and a family history of schizophrenia. A positive family history of diabetes was associated with a positive family history of schizophrenia in those with a psychotic disorder (odds ratio = 1.35, p = 0.01, adjusted for age and gender). The association was different in those with an affective versus non-affective psychosis (odds ratio = 0.613, p = 0.019, adjusted for age and gender) and was significant only in those with a non-affective psychosis, specifically schizophrenia (odds ratio = 1.58, p = 0.005, adjusted for age and sex). Adjustment for demographic factors in those with schizophrenia slightly strengthened the association (odds ratio = 1.74, p = 0.001, adjusted for age, gender, diagnosis, ethnicity, education, employment, income and marital status). Elevated risk for type 2 diabetes in people with schizophrenia is not simply a consequence of antipsychotic medication; type 2 diabetes and schizophrenia share familial risk factors. © The Royal Australian and New Zealand College of Psychiatrists 2015.
    Australian and New Zealand Journal of Psychiatry 07/2015; DOI:10.1177/0004867415595715 · 3.41 Impact Factor
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    • "Psychiatric treatments, specifically pharmacotherapies , may have some protective effect against excess mortality (Weinmann et al. 2009) although evidence suggests that this depends on use of medications according to best practice guidelines (Cullen et al. 2013). In contrast, some second generation antipsychotics may actually pose an elevated risk mediated by metabolic side effects (Newcomer, 2005; Smith et al. 2008; Rummel-Kluge et al. 2010). Much of the disease burden due to opioid dependence and injecting drug use could be averted by scaling up needle and syringe programs (NSPs), opioid substitution treatment and HIV antiretroviral therapy (Degenhardt et al. 2010; Turner et al. 2011). "
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    ABSTRACT: Aims: Mortality-associated burden of disease estimates from the Global Burden of Disease 2010 (GBD 2010) may erroneously lead to the interpretation that premature death in people with mental, neurological and substance use disorders (MNSDs) is inconsequential when evidence shows that people with MNSDs experience a significant reduction in life expectancy. We explore differences between cause-specific and excess mortality of MNSDs estimated by GBD 2010. Methods: GBD 2010 cause-specific death estimates were produced using the International Classification of Diseases death-coding system. Excess mortality (all-cause) was estimated using natural history models. Additional mortality attributed to MNSDs as underlying causes but not captured through GBD 2010 methodology is quantified in the comparative risk assessments. Results: In GBD 2010, MNSDs were estimated to be directly responsible for 840 000 deaths compared with more than 13 million excess deaths using natural history models. Conclusions: Numbers of excess deaths and attributable deaths clearly demonstrate the high degree of mortality associated with these disorders. There is substantial evidence pointing to potential causal pathways for this premature mortality with evidence-based interventions available to address this mortality. The life expectancy gap between persons with MNSDs and the general population is high and should be a focus for health systems reform.
    Epidemiology and Psychiatric Sciences 12/2014; 24(02):1-20. DOI:10.1017/S2045796014000687 · 3.91 Impact Factor
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    • "The DAD contains demographic and clinical information for all patients discharged from any hospital using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10-Canada (ICD-10_CA). APPROACH is an ongoing prospective data collection initiative that has captured detailed clinical information on all patients undergoing cardiac catheterization and subsequent interventions in the province of Alberta, Canada since 1995 [6]. After data collection from the APPROACH database, a data enhancement process verifies patient comorbidities and maximizes data completeness [7] [8]. "
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    ABSTRACT: Background People with schizophrenia are at significantly greater risk of cardiovascular disease-related mortality. We set out to determine if people with and without schizophrenia who undergo coronary artery catheterization differ with respect to coronary anatomy, coronary artery disease management, or outcome. Methods and Results This study used provincial administrative data and a clinical registry that included all individuals who undergo coronary catheterization in Alberta, Canada. Individuals with schizophrenia were identified in hospital discharge data using ICD-9 codes. We identified 271 Albertans with a hospital discharge diagnosis of schizophrenia and a subsequent coronary catheterization and were matched with 1083 controls without schizophrenia that had undergone a coronary catheterization. Extent of coronary disease was assessed using 1) left ventricular ejection fraction; 2) the Duke Jeopardy Score (a valid measure of myocardium at risk for ischemic injury); and 3) a categorical assessment of coronary anatomy risk. People with schizophrenia were less likely to be categorized as high risk on the Duke coronary index (p <. 05) and more likely to be categorized as having a normal coronary anatomy (p < .05). Significant differences in mortality were found among those with and without schizophrenia both before and after adjustment for clinical differences. Conclusions Our results suggest that people with schizophrenia have less severe coronary atherosclerosis, and are less likely to receive revascularization. Despite less severe coronary atherosclerosis, individuals with schizophrenia had a significantly higher mortality following catheterization. Interventions to increase therapeutic adherence and clinical follow up of patients with mental illness may improve health outcomes.
    IJC Heart and Vessels 07/2014; 4(1). DOI:10.1016/j.ijchv.2014.06.009
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