Mental Health Group, University of Southampton
Medical Research Council Environmental Epidemiology Unit, University of Southampton
Correspondence: Dr Steve Brown, Mental Health Group, University of Southampton, Royal South Hants Hospital, Brinton's Terrace, Southampton SO14 0YG, UK. Fax: 023 80234243; e-mail: sb15{at}soton.ac.uk
Declaration of interest Funded by the NHS Executive South and West Region, R & D Directorate. No conflict of interest.
1 One woman aged 66 was inadvertently included.
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ABSTRACT |
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Aims To measure the standardised mortality ratio (SMR) and examine the reasons for any excess mortality in a community cohort with schizophrenia.
Method We carried out a 13-year follow-up of 370 patients with schizophrenia, identifying those who died and their circumstances.
Results Ninety-six per cent of the cohort was traced. There were 79 deaths. The SMRs for all causes (298), for natural (232) and for unnatural causes (1273), were significantly higher than those to be expected in the general population, as were the SMRs for disease of the circulatory, digestive, endocrine, nervous and respiratory systems, suicide and undetermined death. Smoking-related fatal disease was more prominent than in the general population.
Conclusions Some of the excess mortality of schizophrenia could be lessened by reducing patients'smoking and exposure to other environmental risk factors and by improving the management of medical disease, mood disturbance and psychosis.
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INTRODUCTION |
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METHOD |
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Subjects were followed up to 31 December 1994, the cohort census date, and classified as alive, dead or untraced. Alive means evidence from records, professional staff, or interview with relatives or patient; dead means sight of a death certificate or other official document confirming death; untraced, neither of these. The untraced were included in the follow-up period until the date they were lost. Medical and psychiatric history, smoking history, personal circumstances, account and cause of death came from the research record of the 1981 study, hospital case notes, relatives, professional staff, coroner's record and death certificate.
Person-years-at-risk by age and gender were calculated, and multiplied by the appropriate mortality rates for England and Wales, in order to obtain the expected number of deaths (Breslow & Day, 1987; Office of Population Censuses and Surveys, 1981-1994). The number of deaths observed divided by the number of deaths expected and multiplied by 100 gave the standardised mortality ratio (SMR). An increased SMR is statistically significant when the lower confidence interval (CI) (95%) is 100 or more (Gardner & Altman, 1989).
We examined the effects of smoking and social disadvantage by comparing the
SMR of dichotomous groups, dissimilar for smoking and for factors known to
increase mortality in the general population, using 2 analysis
(Breslow & Day, 1987).
Subjects with incomplete data were omitted from the pertinent parts of this
analysis.
The effectiveness of medical care was quantified (Rutstein et al, 1976) by calculating an SMR for those diseases where death is avoidable by appropriate treatment, selected for this purpose in the Chief Medical Officer's (CMO's) annual report (Department of Health, 1994). A high SMR for a disease on this list suggests, but does not prove, substandard care.
Individual deaths were assessed by case note audit (by S.B.). Death was considered preventable when an available effective treatment was not given. Details of each death are available from the authors.
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RESULTS |
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All cause mortality (ICD-9 001-799 and E800-999)
The SMR for all age groups was above the average for the general
population, and fell with increasing age. The all-cause SMR was 298 (CI
236-372), a three-fold increase (Table
2), and the SMR for a first episode of illness was 248 (CI
30-896), based on two deaths out of 27 subjects.
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Mortality was higher in males (Table 2), and in the unemployed, the unmarried and patients from lower social classes (Table 3), but the differences in SMR did not reach statistical significance.
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Natural cause mortality (ICD-9 001-799)
The natural cause SMR (232, CI 176-300), twice that expected, did not
change significantly over the follow-up period. Death from natural causes
accounted for two-thirds (63%) of the excess mortality: 80% of these deaths
were from neoplastic, circulatory or respiratory disease, similar to the
distribution of cause of death in the general population
(Office of Health Economics,
1992). The SMRs from cerebrovascular disease, diabetes and
epilepsy were much increased (Table
4).
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Avoidable natural deaths
The SMR (468, CI 172-1020) of those causes designated
avoidable by the CMO was increased nearly five times. Four of
the six avoidable deaths, all in people aged 35-64, were from
hypertension and/or cerebrovascular disease, and two were from surgical
diseases.
The SMR was significantly raised for smokers, but not for non-smokers (Table 3), and for smoking-related disease (SMR 181, CI 112-277; Royal College of Physicians, 1971). The SMR for lung cancer (208, CI 68-485) was twice the expected value.
Audit of the case notes suggested a number of mechanisms underlying the excess natural mortality.
Failed recognition of medical disease by patient or carer
A 41-year-old man died from acute pulmonary oedema shortly after leaving
the casualty department, having not waited to see a doctor.
A 63-year-old woman with treatment-resistant schizophrenia and learning disability died in a rest home from acute intestinal obstruction caused by old surgical adhesions.
A 63-year-old man died alone at home from acute intestinal obstruction caused by a scrotal hernia, while on the waiting list for elective repair. He had been managed conservatively in hospital when the hernia obstructed 4 months earlier.
Failed recognition of medical disease is also a plausible explanation for some of the excess cancer mortality, as five cancers were disseminated at presentation: two, in itinerants unregistered with general practitioners (GPs), were detected at psychiatric admission.
Missed medical diagnosis
Two women, resident in long-stay psychiatric wards, died from lobar
pneumonia, having been examined by a doctor shortly before death. Neither
appeared particularly unwell. In neither case was pneumonia diagnosed or
antibiotics prescribed.
A 57-year-old man died in hospital after a cardiac arrest. Psychiatric out-patient notes detailed increasing confusion in the 2 weeks before admission to hospital, stuporous and hypothermic. Hypothyroidism was confirmed by thyroid function tests returned after death.
Poor treatment compliance
A 55-year-old itinerant woman, with known diabetes, not registered with a
GP and refusing psychiatric contact, died from diabetic ketoacidosis.
The high SMR from epilepsy, diabetes, cerebrovascular and respiratory diseases (Table 4) may also be at least partly due to poor treatment compliance.
Treatment refusal
A 61-year-old man died a year after refusing potentially curative surgery
for bowel cancer. Psychiatrists found no evidence of psychosis but could not
persuade him to accept surgery.
A 70-year-old woman died from dehydration after refusing food and drink following a fractured femur.
Lifestyle
A 75-year-old woman died after physicians refused life support treatment,
citing poor quality of life. Her elderly husband found her agitation difficult
to manage and kept her in bed, inactive and under-stimulated. Psychiatrists
were unable to intervene effectively. Bed sores progressed to septicaemia and
multiple organ failure.
Mortality from unnatural causes (ICD-9 E800-999)
The unnatural cause SMR was 1273 (CI 767-1988), 12 times that expected.
Death from unnatural causes accounted for 33% of the excess mortality.
Fourteen of the 19 unnatural deaths were due to suicide, three to accident and
in two cases the causes were undetermined. The unnatural deaths occurred in
the early years of follow-up: six in year one, 13 by the end of year three. Of
the 14 suicides, five died in year one, 12 by the end of year five. Of the ten
deaths of subjects aged below 40, nine were unnatural.
Suicide
Ten of the 14 people who committed suicide were under treatment by the
psychiatric services at the time of death, three had refused treatment and one
had been discharged from hospital without follow-up, 2 weeks before death. Of
the ten under treatment, six were in-patients, three were out-patients, and
one was a day patient. The six in-patient suicides all used violent methods.
Four out-patient suicides used violent methods and four took poison.
Ten of these subjects had previously attempted suicide, five repeatedly. Five had shown evidence of distress or low mood shortly before death. One in-patient killed himself despite regular observation, and one died 2 days after observations were relaxed. None of the other victims had had a recent risk assessment. Case note scrutiny suggested that the in-patient and day patient suicides might have been prevented.
Accident
One out-patient death, from benzatropine toxicity, was probably a missed
suicide. Two others, although probably accidental, appeared causally related
to schizophrenia.
A 48-year-old man, a heavy smoker living with elderly parents, died of asphyxia in a bedroom fire. Depot anti-psychotic medication had been stopped after years of stability in an attempt to relieve a severe drug-induced extrapyramidal syndrome. He was readmitted because of disorganised conduct but discharged himself, against advice, a week before his death.
A 64-year-old man with mainly negative symptoms, compliant with medication and living quietly in a group home, was found dead from hypothermia in a forest 20 miles away, to which he had apparently walked.
Undetermined cause of death
One undetermined death was probably a suicide. A 55-year-old man with a
history of treatment-resistant schizophrenia, substance misuse and attempted
suicide died from a self-administered overdose of amitriptyline, which he took
at home after absconding from hospital.
The other undetermined death was of a 40-year-old man, who died without further psychiatric contact 3 years after recruitment into the study, from a fall or jump from his flat, and this drew an explicit comment from the coroner that there was insufficient evidence of intent to determine causality.
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DISCUSSION |
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Selection bias
The inclusion criteria were similar to those in most comparable cohorts.
The largest source of bias probably came from the use of a prevalence rather
than an incidence cohort. This meant that at recruitment, 343 (93%) subjects
had already survived the period of greatest excess mortality
(Mortensen & Juel, 1993). Most were already middle-aged and again at lower risk
(Brown, 1997).
Forty-seven potential subjects, who were long-stay hospital patients in 1981 (Gibbons et al, 1984), probably with a relatively low SMR (Brown, 1997), were excluded as they could not be reliably identified. The cohort was further unrepresentative of the local population with schizophrenia in that it excluded patients who were not in contact with the psychiatric services during the index year, those with unrecognised schizophrenia and those with significant drug or alcohol misuse.
Most patients who avoid contact with specialist mental health services for a year will be well and therefore at low risk of premature death. Most with unrecognised schizophrenia probably have early disease and a high SMR (Mortensen & Juel, 1993). Patients with comorbid substance misuse also have a high SMR (Harris & Barraclough, 1998). The net effect of these sources of bias was probably to underestimate disease SMR.
Follow-up
We checked with GPs, other health professionals, family and friends to find
out whether subjects were dead or alive. Death certificates were matched to
National Health Service (NHS) central records, using family and given name,
date and place of birth, place of death and NHS number (where we knew it). The
matches were then verified, the available detail suggesting that matches were
correct. Completeness of follow-up was unexceptional compared to similar
studies (Anderson et al,
1991; Kelly et al,
1998).
The causes of death are probably more accurate than one would find in a sample of the general population, as the rates of post-mortem examination (62 and 22%), and coroner's inquests (25 and 3.5%) were many times higher (Home Office Statistical Bulletin, 1994). These rates are explained by the large number of deaths referred to the coroner, either because they were unnatural (n=19) or because no medical officer had seen the deceased in their final illness (n=30).
Statistical analysis
Mortality rates in the south of England are lower than the average for
England and Wales (Office of Population
Censuses and Surveys, 1996); hence the use of national reference
data will have underestimated SMRs.
Calculation of an avoidable natural SMR followed the procedure used in the CMO's annual report. Designed to give a rough measure of the quality of medical treatment, this analysis is based on deaths from selected common diseases for which effective treatment is available. It misses potentially preventable deaths from rarer causes, and deaths where the immediate (though not the underlying) cause was treatable, and therefore probably underestimates avoidable mortality.
Smoking histories, obtained from initial case records, may have been unreliable and may have changed over the course of the study. Our results probably followed general population surveys in underestimating the prevalence of cigarette smoking (Bennett et al, 1995) and thereby its effect on mortality.
Care assessment
We obtained hospital case notes on all but the two patients who died
abroad. Case note audit was retrospective and subject to recorder and
investigator bias. Designation of individual deaths as preventable was
subjective and conservative; vignettes were chosen to illustrate points rather
than as measures of the prevalence of particular mechanisms. We cannot know
whether anyone would have survived with better treatment or whether the
prevalence of such events differs from that in the general population.
Overall mortality
The SMR was higher than in any previous published cohort of subjects
measured at varying points in a schizophrenic illness
(Brown, 1997); however, the
cohort was relatively small and some SMRs have wide confidence intervals.
Previous studies do not contain enough clinical data to know whether the high
mortality might be explained by selection or methodology. As in previous
studies, about two-thirds of the extra deaths were from natural causes
(Brown, 1997).
Kendler's study of twins suggests that most unnatural deaths of subjects with schizophrenia are from suicide, while the pattern of natural mortality is best explained by altered exposure to environmental risk factors (Kendler, 1986). The non-significant variation of SMR with social class, employment and marital status supports previous suggestions from mixed diagnostic cohorts (Babigian & Odoroff, 1969; Baxter, 1996) that social disadvantage explains only a small part of the excess mortality. This conclusion requires qualification, as many subjects had declined in the social scale during the follow-up years, and hence analysis, based on status at the outset, probably accentuated differences.
The causes of death were similar to those seen in similar cohorts (Lesage et al, 1990; Anderson et al, 1991). Two subjects who died in status epilepticus may have had brain pathology which caused both epilepsy and schizophrenia. No other deaths appeared likely to be due to misclassified organic psychosis. Bronchopneumonia was a particularly common terminal event, usually associated with the underlying pathology. As reference mortality statistics are based on the underlying rather than the immediate cause of death (World Health Organization, 1977), we do not know whether this finding is significant.
Preventable natural mortality
Analysis of case notes suggests that improved recognition of acute medical
disease, better treatment of chronic medical disease and better treatment
compliance might prevent some deaths. The vignettes also suggest that some of
the avoidable deaths would in practice have been very difficult
to prevent. Doctors' ability to supervise treatment is limited, while
competent patients are entitled to refuse optimal treatment.
Unhealthy lifestyles
Our study suggests that most of the excess natural mortality of modern
community samples is due to cigarette smoking, and that helping patients to
stop smoking should be a priority for doctors and health service planners.
Psychiatrists rarely discuss patients' smoking
(Lawrie et al, 1995),
despite evidence that programmes to help stop smoking can be effective in
schizophrenia (Ziedonis & George,
1997).
Many patients with schizophrenia eat poor diets and are obese (McCreadie et al, 1998). We did not have the information to assess if diet, self-care and exercise affected the mortality of our subjects. However, when interviewed in 1996, survivors were eating a poor diet and taking little exercise (Brown et al, 1999). If survivors were selected for health, then the deceased probably also had unhealthy lifestyles. No deaths were directly due to drug or alcohol misuse, but it must be remembered that the original study criteria excluded patients with significant substance misuse.
Psychiatric treatment
No deaths were unequivocally due to psychiatric treatments. Neuroleptic
drugs may have contributed to the death from aspiration pneumonia of a
62-year-old woman with cerebrovascular disease. Similar deaths were noted by
both Lesage et al
(1990) and Anderson et
al (1991), a striking
finding considering the size of the cohorts. Neuroleptic drugs may also
exacerbate diabetes, epilepsy and chronic respiratory disease
(Mortensen & Juel,
1990).
Unnatural mortality
The unnatural mortality rate was significantly increased. As in other
series, most unnatural deaths were from suicide
(Brown, 1997), though
accidental and undetermined deaths were also increased.
Suicide
The high, but not exceptional, suicide mortality of the Southampton cohort
is not explained by its socio-demographic composition. The characteristics of
the victims and circumstances of death fit broadly with previous findings, but
the numbers were too small for reliable statistical analysis. The high
proportion of early in-patient suicides
(Barner-Rasmussen, 1986;
Heilä et
al, 1997) may have been due to clustering around psychiatric
contact. It may on the other hand reflect the unsettling effects of moving
from the area mental hospital to a new non-purpose-built unit in the grounds
of an inner-city district general hospital (DGH) shortly before the cohort was
first enrolled. Staff had no previous experience of running a DGH unit, and
there were probably too few beds.
Case notes suggest that one of four suicides, not in contact with psychiatric services, might have been re-engaged by a more assertive approach. The Care Programme Approach (CPA) might have prevented the suicide of a patient who was discharged from hospital without follow-up. It is unrealistic to expect to prevent all suicides in those with schizophrenia, as some occurred without warning or among patients who rejected psychiatric contact.
Recommendations
Psychiatry, as a branch of medicine, should aim to treat disease.
Mortality, the most objective measure of disease outcome and effectiveness of
medical treatment, should continue to be monitored, to assess the impact of
national policy changes and the performance of local units. Further large,
prospective cohort studies are needed to examine the mortality from specific
causes and to test hypotheses about aetiology. Individual follow-up studies
are needed to identify treatment deficiencies and suggest improvements in
clinical practice.
Our findings suggest that most of the excess mortality of schizophrenia can be explained by known mechanisms, and hence should be susceptible to currently available interventions. In particular, psychiatrists should ensure that they maintain their diagnostic skills, and mental health services should be assertive in addressing patients' smoking, alcohol use, diet and other lifestyle factors.
Whether psychiatrists or GPs are best placed to treat medical disease in the seriously mentally ill is uncertain; however, the responsibility for medical treatment should be explicitly allocated. Doctors should consider regular physical examinations of people who might fail to recognise that they were ill and to seek treatment. They should also consider invoking the Mental Health Act when patients' mental state is seriously jeopardising their physical health.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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REFERENCES |
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Received for publication November 29, 1999. Revision received March 13, 2000. Accepted for publication March 15, 2000.