Mortality in severe mental illness: then and now Psychobiology Research Group Prof Nicol Ferrier Emeritus Professor of Psychiatry Newcastle University
Mortality associated with severe mental illness People with psychosis die on average 15 ‐ 20 years younger than the general population (e.g. McGrath et al, 2008) Schizophrenia More than 20-fold increased risk for death by suicide. Increase in deaths from infectious diseases and accidents. People with schizophrenia are up to 50% more likely to have type 2 diabetes mellitus and obesity. 70% of patients with schizophrenia, compared with approximately 50% of the general population, die of coronary heart disease (CHD). SMR for cardiovascular disease (CVD) deaths is 2-4 times age matched population. Bipolar disorder More than 20-fold increased risk for death by suicide Patients with untreated illness have >4-fold higher SMR CVD is the leading causes of premature mortality in this population but hospital admissions for CVD treatment were only slightly increased in BD compared to the general population Evidence that the mortality gap is widening across the world. In UK, gap gradually increased from 2005 and rapidly from 2010 (Hayes et al, 2017)
Pre Premat ature Dea Death ‐ Causes Lifestyle Issues -More sedentary -Less likely to eat fruit and vegetables -Twice as likely to develop type II diabetes mellitus -2-3 times more likely to be obese Smoking -More likely to smoke -76% with first episode psychosis (FEP) were regular smokers -Those with schizophrenia have a 10 fold increased death rate from respiratory disease Inverse Care -Discrimination by health professionals -Do not receive optimal physical health care -Lowered reporting of physical symptoms Genetic Factors -15% of drug-naïve individuals with first-episode psychosis have elevated fasting glucose levels, high levels of insulin and cortisol, and three times as much intra-abdominal fat as age and Body Mass Index -matched control subjects
Cardiovascular disease and deaths in severe mental illness UK data:- 46,136 people with SMI and 300,426 without SMI ( Osborn et al. 2007 ) Hazard ratios (95% CI) in age groups with SMI vs controls :- CHD mortality Stroke deaths 18-49 3.22 (1.99-5.21) 2.53 (0.99-6.47) 50 -75 1.86 (1.63-2.12) 1.89 (1.50-2.38) >75 1.05 (0.92-1.19) 1.34 (1.17-1.54) Correll et al, May 2017 . Meta-analysis of ~3.2 M SMI patients and ~113.3M controls CVD (1.95), cerebrovascular disease (1.57) , CCF (1.71*) and death due to CVD (2.45) all increased. * Unadjusted and cross-sectional
CV risk factors: overview The Framingham Study Cohort* 5 14 Multiple risk factors 12 4 10 Odds ratios 8 Single risk factors 6 3 4 2 2 0 Smoking Smoking Smoking BMI >27 Smoking TC >220 DM HTN Smoking + BMI + BMI + BMI + BMI + TC >220 + TC >220 + TC >220 + DM + DM + HTN BMI: body mass index, DM: diabetes mellitus, HTN: hypertension, TC: total cholesterol. *Data using Framingham study cohort. Dawber et al, Am J Public Health, 1951; 41: 279 Wilson et al, Circulation, 1998; 97: 1837–47
Antipsychotics and Metabolic Dysfunction • A wealth of evidence exists showing link between antipsychotic use and metabolic dysfunction (Starrenburg et al, 2009) • “second generation” ‘worse’ than “first generation” • H1, 5HT2-C, α 2, β 3 receptors (regulation of food intake) • 5HT1-A, M3, α 2 receptors (present in β cell in Pancreas – regulation of insulin release, and insulin sensitivity) (Adapted from Leucht et al, 2013)
Cardiovascular disease and deaths in severe mental illness Osborn et al. 2007 UK data:- 46,136 people with SMI and 300,426 without SMI HRs for CHD mortality in 50-75 age group of SMI (95% CI) Not on APs 1.4 (1.1-1.8) On APs 2.0 (1.7-2.3) p=0.009 Low dose 1.5 (1.1-1.8) High dose 2.5 (2.0-3.1) p<0.001 Correll et al, May 2017 . CVD incidence increased with higher AP use, higher BMI and baseline CVD.
Mortality associated with schizophrenia Role of antipsychotics • There is little evidence that long-term exposure to antipsychotics increases mortality in schizophrenia. • No increased CVD mortality in placebo controlled trials • Mortality increased in drug free populations in both cross-sectional and prospective studies but high quality data lacking. • Some positive dose-response studies find increased CVD deaths in patients on higher AP doses but a major confounding factor may be a higher risk factor load for somatic disorders in the most severely mentally ill. More rigorously designed, prospective studies are urgently needed.
Recent developments: ‐ First Episode Psychosis (FEP) • FEP strongly associated with insulin resistance (IR) (OR=5.14) compared to matched controls, after relevant adjustments. Weaker and less convincing associations with lipids (low HDL and raised triglycerides were weakly associated with FEP). (Perry et al, 2016) • Poor glycaemic control linked with increased levels of CRP, IL6, TNF α , IL1 β (Dandona P et al , (2004) • IR significantly associated with pre-clinical psychotic symptoms (OR=2.32) after adjusting for: sex, ethnicity, gestational age, birthweight, physical activity, BMI, smoking, antipsychotic medication. No association lipids / metabolic syndrome – suggests IR comes first. The relationship was non-linear, and exponential • IL-6 was found to act as a ‘moderator’ in the relationship, suggesting that inflammation, IR and psychotic symptoms are closely linked Even before the onset of psychotic illness, metabolic dysfunction is prominent. -This effect is driven by dysglycaemia (insulin resistance) -Raised IL-6 interacts with IR to cause psychotic symptoms
Morbidity and mortality in C19 asylums • Many early reports that the insane died in excess and prematurely. Burrows (1828) “insanity tends to the shortening of human life”. • Farr (1841) started data collection and confirmed the high mortality of asylum inmates compared to the general population. Death rates (deaths/inmate) were 5 ‐ 7 times higher that of matched populations and the “mortality gap” ~ 15 years. Some of the excess mortality linked to deaths from conditions like GPI, epilepsy and imbecility but it was also found in mania and melancholia. • More marked in men, early in admission, in migrants and the malnourished. Lower is some asylums e.g. the Retreat in York • These issues led, in part, to the development of asylums and subsequently to the 1870 recommendation from the Commissioners in Lunacy that asylums perform PMs on all deaths.
Mortality in Severe Mental Illness in Victorian asylums General Adult Population. Dying to Get Out of the Asylum: Mortality and Madness in Four Mental Hospitals in Victorian Canada, c. 1841–1891 Wright D, Jacklin L, Themeles T (2013) Bulletin of the History of Medicine, 87, 590 ‐ 621
Moulsford/Berkshire Asylum The Boroughs of Reading and Newbury built Moulsford Asylum by the Thames and the first patients were admitted in 1870. The asylum was designed to accommodate 285 patients but was almost full to capacity within the first year. The asylum was extended in 1880 to accommodate 609 patients and in asylum was expanded to a capacity of 800. In 1897 its name was changed from Moulsford Asylum to the Berkshire Lunatic Asylum. In 1948, when it was incorporated into the National Health Service, the name was changed again to Fair Mile Hospital. In 2003 Fair Mile was closed as it no longer provided appropriate accommodation.
Sunnyside Royal Hospital, Montrose Originally founded in 1781 by Susan Carnegie as the Montrose Lunatic Asylum, Infirmary & Dispensary . Obtained a Royal Charter in 1810. In 1834, the Governors of the asylum, carrying out the wishes of Mrs Carnegie (who had strongly advocated the appointment of a medical specialist in insanity) appointed the phrenologist William Browne as medical superintendent. In 1858, a new improved asylum was completed but overcrowding was a problem. The asylum's patient numbers had grown to 670 by 1900 leading to further building. The site was officially closed in late 2011 and most patients were sent to a new £20 million build at Stracathro Hospital - the Susan Carnegie Centre. Sunnyside was open for 230 years before its closure and was the oldest psychiatric hospital in Scotland.
Sunnyside Asylum Numbers of inmates and deaths 1892 ‐ 1901 Death 9% 11% 8% rate
Berkshire Asylum Numbers of inmates and deaths 1896 ‐ 1905 Death 8% 13% 9% rate
Notes on numbers and deaths • Both asylums had very favourable Commissioner reports (including the staff and the food) although it was agreed there was overcrowding. • Recurrent mention of and concern about admissions with no hope of recovery in both asylums “unfavourable admissions have led to the lowest recovery rates in the history of the asylum” and “overcrowding is telling on the health of patients”. • Frequent reports of typhoid, dysentery and scarlet fever in Berkshire in patients and staff. Great concern over water supply and sanitation. • Both asylums had somewhat raised death rates compared to the norm. Fluctuations in Berkshire partly related to infectious GI diseases and partly due to nature of admissions. It was noted that aged admissions increased the death rate because of the “to be expected course of events”
Sunnyside Asylum, Montrose Deaths and PMs 1892 ‐ 1901
Berkshire Asylum Deaths and PMs 1896 ‐ 1905
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