Excess mortality of schizophrenia. A meta-analysis.

S Brown
BJP 1997, 171:502-508.
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Excessmortality of schizophrenia
A meta-analysis
STEVE BROWN
Background Thispaperpresentsa
structured review ofthe published
information on the mortality of
schizophrenia.
Method A meta-analysis
ofthe
literature.
Results Schizophrenia
hasa
significantly increased mortality from
natural and unnatural causes.Twenty-eight
percentofthe excessmortalityis
attributable to suicide and 2% to accidents.
Therestofthe excessmortalityisfrom
the same broad range ofconditions which
cause deaths in the general population.
Further interpretation is hampered by
confounding variables, wide confidence
intervals and reservations about
generalising from individual cohorts.
Conclusions The availableevidence
suggests that schizophrenia is associated
with a large increased mortality from
suicide and a moderate increased mortality
from natural causes.A number of possible
interventions have been identified, but
we do not yet have reliable means of
detecting any changes in mortality which
might result.
502
Schizophrenia is associated with an in
creased risk of premature death (Mortensen
& Juel, i990, i993). Improving the life
expectancy of sufferers should be a priority
of the psychiatric services. This will require
an understanding of the causes of the excess
deaths. This paper presents the first meta
analysis of the mortality of schizophrenia. It
discusses the methodology and limitations
of current work, places contemporary stud
ies in a historical framework and offers
suggestions for further research.
DEVELOPMENT OF
MORTALITY STUDIES
IN SCHIZOPHRENIA
The first commentary on the mortality of
lunacy in England and Wales dates from the
17th century (Graunt, 1662). The earliest
systematic measurement was probably in
184i, when William Farr reported that the
mortality of lunatics in England and Wales
varied between three and 14 times that of
the general population. He concluded that
some of the excess deaths “¿may be fairly
ascribed to insanity―,but that most resulted
from the conditions in the asylums. About a
quarter of Victorian asylum patients would
probably now receive a diagnosis of schizo
phrenia (Turner, 1990), hence the contem
porary mortality of schizophrenia was
probably increased.
Kraepelin commented of dementia prae
cox, that “¿life is threatened only very
slightly―.He noted that suicide occurred in
the acute and chronic stages, and speculated
that negativism, inadequate diet and poor
cooperation with treatment of concurrent
medical disorders also contributed to the
increased mortality (Kraepelin, 1919). Eugen
Bleuler (1950) calculated that schizophrenia
was associated with an excess mortality of
1.4: 1. Deaths resulted from “¿the indirect
consequences of psychosis: refusal of food,
intentional or unintentional injuries, suicide,
tuberculosis and other diseases resulting
from unhygienic ways of life―.The mortality
in the asylums during the first part of this
century was described in three large studies
from the USA (Malzburg, 1934), Norway
(ødegârd, 1936) and Sweden (Alström,
1942). These authors used the standardised
mortality ratio (SMR), calculated by dividing
the observed mortality of a cohort by the
expected mortality of an age- and gender
matched cohort of the general population, to
measure variations in mortality. Each found
a significantly raised SMR in schizophrenia
of between 2i0 and 400. Excess mortality
was greater among females and in the acute
stages of the disease, and lessened with
increasing age and length of stay. Most of
the excess deaths were from pulmonary
tuberculosis and pneumonia, consequences
of overcrowding, malnutrition and other
deficiencies of the asylums. Suicide was
increased but accounted for only a few
deaths. During the First World War many
asylum patients in England and Wales died
from tuberculosis secondary to malnutrition
(Crammer, 1992), while in Nazi Germany
many were systematically murdered by the
state (Burleigh, 1994).
The treatments of the pre-neuroleptic era
also caused many deaths. Leucotomy had an
operative mortality of between 0.8 and 2.5%
(Swayze, 1995), while the mortality of insulin
coma therapy was 0.6% and that of cardia
zol-induced convulsions 0. 1% (Henderson &
Gillespie, 1952). Treatment-related deaths
accounted for 17% of the mortality of a
cohort followed at the Burgholzi Hospital
from 1942 to 1965 (Bleuler, 1978).
The treatment of schizophrenia changed
after the war, as a result of de-institutional
isation and the subsequent introduction of
effective antipsychotic drugs. Most modem
patients with schizophrenia, therefore, cx
perience very different environmental con
ditions from their predecessors. It is not
possible to define a precise point at which
these changes occurred; however, the intro
duction of chlorpromazine in 1952 provides
a convenient starting point for the analysis
of contemporary mortality.
CONTEMPORARY STUDIES OF
SCHIZOPHRENIA MORTALITY
Record linkage studies
Record linkage studies, the most common
method of measuring mental illness mortal
ity, use identifying characteristics (usually
name and date of birth) to link psychiatric
case records with population or death
registers. The introduction of computerised The data are from official records and should (c) there was a stated loss to follow-up of
databases has allowed large cohorts to be be complete; however, patients who leave less than 15%.
studied, with consequently high statistical hospital are lost to follow-up. The cohorts The analysis was restricted to cohorts
power. The validity of the results depends are therefore poorly representative of the from North America, The Netherlands,
on the accuracy of original entries on the population with schizophrenia. Israel, Scandinavia and the UK as no other
databases and on the accuracy of the record studies met the inclusion criteria. Where
linkage process. The size of error from these subjects were included in more than one
THE META-ANALYSIS
sources varies from study to study, and is study, the data come from the paper
rarely discussed in satisfactory detail. describing the largest cohort (Black, 1988;
Papers were identified through searches of
the Medline and BIDS Gateway databases Mortensen & Juel, 1990, 1993).
Individual follow-up studies from January 1986 to December 1996, using Aggregate SMRs were calculated by
the key-words ‘¿mortality', ‘¿outcome' and dividing the sum of the observed deaths by
In these studies subjects are traced personally.
‘¿follow-up'
with ‘¿schizophrenia'and ‘¿mental the sum of the expected deaths, and multi
This is time-consuming, but provides the
illness'. The citations in each paper were plying the result by 100. Confidence inter
details about illness, treatment, and outcome
then checked until no further references were vals and significance statistics were
which explain individual deaths. Only three
forthcoming. The meta-analysis was re calculated from the Poisson distribution
individual follow-up studies that presented
stricted to the English and French languages, (Gardener & Altman, 1989), and hetero
results in the form of SMRs have been
peer-reviewed studies, of more than 100 geneity of the cohorts measured as described
published (Martin et al, 1985; Lesage et a!,
individuals with schizophrenia, recruited by Thompson (1993).
1990; Anderson et a!, 1991). These studies
analysed a total of 85 deaths, hence the since 1952, which met the following criteria:
generalisability ofthe findings is questionable. RESULTS
(a) the paper included the number of
observed and expected deaths, or The aggregate mortality
Analysis of in-patient registers contained sufficient details to allow of schizophrenia
these figures to be calculated;
These studies use information from in-patient Mortality was increased in every study
registers to measure the mortality of hospital (b) the cohort was followed up for at least included in the meta-analysis (Table 1),
populations (Giel et a!, 1978; Brook, 1985). two years; and though the increase was non-significant in

TableI All-cause
mortalityofschizophrenia

AuthorsCountryDiagnostic
Cl)(years)Babigian ofcohortLength of (95%
criteriaMethodSize follow-upObserved
deathsExpecteddeathsSMR

(160—l89)Weiner
& Odoroff(1969)USACase registerRecord linkage8080'0-654l3l075
& Marvit (l977)USACase
(164—210)Giel registerRecord linkage6890219I 6.388
eta! (1978)NetherlandsCase
16—l36)Eastwood registerIn-patient records8142253742626 (I
eta! (1982)CanadaICD—8Record
(57—273)Haugland linkage82974.845
eta! (l983)USADSM—lllRecord
l0—270)Herrmaneta/(1983)UKICD—8Record linkage3513.520I I181 (I
linkage59245729.6l92(l46—246)Brook(l985)NetherlandsCaseregisterln-patientrecords52262486305l59(l45—l74)Wood

l)*Allebeck
eta! (l985)USADSM—lllRecord linkage8779'570937987 (l74—20
& Wistedt (l986)SwedenICD—9Record linkageI
(209_27l)*Black(l988)USAICD—9Recordlinkage8910—10457.8260(178—358)Hassall 901023196.5239

(l34—2l7)Zilberetal(1989)IsraelICD—9Recordlinkage9178'58l6395207(l92_22l)*Mortensen
eta! (1988)UKCase registerRecord linkage6952—I I6839.2173

&Juel (l990)Denmark‘Kraepelinian linkage6l520—3045693882I

l4—l22)Andersonetal(l991)UKICD—9Follow-up5322—l46927.6249(l94—3l2)Newman 18(I
lines'Record

& Bland (1991)CanadaICD—9Record

(23l—290)Mortensen linkage36230—lO30 II l6259
& Juel ( I993)DenmarkICD—8Record linkage9 I56I 0—
I8I
5_354)*Amaddeoetal(l995)ItalyICD—9Recordlinkage305'0—lO23l3.ll76(lll—255)Baxter(l996)UKICD—9Record I00329334 (3 I

linkagel398l0—l846229l.3l59(l44@l73)*Total66

161lO 2606788.2ISI (l48—l54)

Variationfromexpectedvaluesignificantat 5%level.
I. Calculatedfrom datasuppliedinthetext.

503
 one small cohort (Eastwood et a!, 1982). Age Diagnostic criteria and subtypes
The meta-analysis produced an aggregate The SMR in schizophrenia appears to of schizophrenia
crude mortality rate (CMR) of 189 deaths/ decrease exponentially with age (Fig. 1). This The aggregate SMR of narrowly defined
10 000 population per year, an aggregate is largely due to a high rate of suicide in the (ICD—9 or DSM—III) schizophrenia was
SMR of 151 (95% CI 148—154) and a 10- young (Anderson et a!, 1991; Newman & significantly lower (SMR 138, 95% CI
year survival of 81%. Bland, 1991; Mortensen & Juel, 1993). The 135—142) than that of broadly defined
natural-cause SMR probably also falls with schizophrenia (SMR 193, 95% CI 186—
Trends in mortality age, but the slope is gradual (Newman & 200), but the difference may be due to
Bland, 1991; Mortensen & Juel, 1993). confounding variables. Mortality is prob
Two Danish studies which measured the
ably increased in all the subtypes of schizo
five-year SMR in successive national cohorts
phrenia. Comparison of the aggregate
suggest that the SMR is rising in the first
mortality of different subtypes was not
episode of schizophrenia (Munk-Jørgensen
possible as a different classification system
& Mortensen, 1992), but falling in chronic
was used in each study which addressed this
schizophrenia (Licht et a!, 1993). This meta
Length of follow-up issue.
analysis found a significantly higher
(P<0.001) aggregate SMR from studies The all-cause SMR fell incrementally over
published in the 1980s (SMR 191, 95% CI the five years following a first episode of
183—199),than from studies published in schizophrenia (Munk-Jørgensen & Morten
the 1970s (SMR 152, 95% CI 144—160),or sen, 1992), and fell with length of follow
1990s (SMR 140, 95% CI 137—143), but up in most (Black, 1988; Hassall et a!,
2o@.
the differences may be due to confounding 1988; Newman & Bland, 1991), though
variables. not all (Allebeck & Wistedt, 1986) cohorts
@ recruited later in their illness. This was 1000 .

@ largely due to a clustering of suicides at the . ..

@ Gender start of follow-up (Black, 1988; Hassall et :‘s...@. •¿
•¿
@ 0, -.-
10 20 30 40 50 60 70 50 90
The male unnatural-cause SMR was signifi a!, 1988; Newman & Bland, 1991; Mor
cantly higher than the female figure but tensen & Juel, 1993). There is no direct Mid-point of age group (years)

there was no gender difference in natural evidence that the natural-cause SMR falls
cause mortality (Table 2). This resulted in a with length of follow-up; however, it was Fig. I Variation in schizophrenia mortality with age.

small but significantly higher overall male significantly lower in the Danish national References:Gieletal (1978);Brook(1985);Black
mortality (aggregate male SMR 148, 95% cohort with chronic schizophrenia than in (1988);Hassall
eta!(1988);Zilberetal (l989);
CI 144—152;aggregate female SMR 139, the equivalent first-episode cohort (Mor Andersoneta! (1991);Newman& Bland(1991);
95% CI 134—144). tensen & Juel, 1990, 1993). Morensen&Juel(1993).

Table 2 Mortality of schizophrenia

by ICD—9
category(categoriesinwhichfewer than20 deathswere recordedhavenot beenanalysedseparately)

ICD—9categoryMaleFemaleTotalObserved

ExpectedSMR(95%Cl)Allcauses ExpectedSMR(95%Cl)Observed ExpectedSMR(95%Cl)Observed

257l.5 2601.4 260 6788.2 (l48_l54)*

All natural causes (00 —¿799) 2443 990.8 23 (I l8_l28)* 2566 2055.8 125(l20@l30)* 5956 4492.l l34 (l3l_l37)*
Cardiovasculardisease 057 944 l12(l05_l19)* 888 814 l09(l02_1I6)* 2029 835.6 llo(lO5—lls)
(390—429)
Cerebrovasculardisease 225 247.4 91 (79—103) 245 347.5 70(6l_79)* 490 607.6 81 (73_87)*
(430—438)
Respiratorydisease (460—519) 308 148.2 208 (185_23l)* 315 127.4 247 (22l_275)* 634 280.2 226 (209_244)*
Neoplastic disease ( I40—SI9) 5 I3 596.0 86 (78—93) 589 544 I08 (99—
I I7) I2 I3 I25 I.0 97 (9 I—¿
I02)
Digestivediseases(520—579) 141 67.7 208(l75@@244)* 27 77.9 63 (l35_l92)* 278 50.0 l85(l64@208)*
Genito-urinarydisease(580—629) 98 54.5 l80(l45—217) 64 38.7 165(137_208)* 168 04.5 161(137_l86)*
Other diseases (I —¿389,
630—799) 356 204.6 I74 (I 56—
I92)* 422 265.2 I59 (I 44—
I75) 809 480.9 I68 (I 57—
I80)
Allunnaturalcauses 715 140.6 508(47l_546)* 351 lOl.8 345(3l0@382)* 1160 272.6 426(402—45l)
(E800—E999)
Accidents (E800—E949) 217 02.6 2l I (l84@240)* 62 75.3 215 (l54_286)* 443 204.8 216 (l96_236)*
Suicide(E950-E959)3819 650 68.0l48(144—l52)
956(884_lO3l)*3605 231 34.3l39(l34@l44)*
673(59l_763)*10 896 106.9ISI
838(784@894)*

Variation from expected value significant at 5% level.

References:Eastwood etol (1982);Hermann etal (1983):Brook (1985);Allebeck & Wistedt (1986);Black (1988);Zilber (l989): Mortensen &juel (1990);Newman & Bland (1991);Mortensen
& juel (1993).

504
Natural-cause mortality Newman & Bland, 1991). The excess ulcer however, significantly fewer people with
Eighty per cent of people with schizophrenia deaths were probably secondary to alcohol schizophrenia drive, and the risk of accident

die from natural causes (Table 2), compared

with 97% of the general population (Office
of Population Censuses and Surveys, 1995).
Natural deaths account for about 59% of
the excess mortality of schizophrenia with
an aggregate SMR of 134 (95% CI 131—
137), and are significantly increased
males (SMR 123, 95% CI 118—128)and
females (SMR 125, 95% CI 120—130).
The aggregate SMR is higher than either
of the gender-specific figures as it includes
780 deaths from an Israeli cohort (Zilber et
a!, 1989) in which mortality was not
analysed by gender. This study found an
unusually high SMR from natural causes,
principally infectious diseases, and low SMR
from unnatural causes, for reasons which
are unclear.
People with schizophrenia die from the
same natural causes as the rest of the
general population (Table 2). Individual
studies have found raised SMRs from a
variety of specific causes; however, some of
these may be chance associations. The only
replicated findings are raised male SMRs
from peptic ulcer (Weiner & Marvit, 1977;
Newman & Bland, 1991) and pneumonia
(Weiner & Marvit, 1977; Herrman et a!,
1983; Brook, 1985; Newman & Bland,
1991), and raised female SMR from pneu
monia (Herrman et a!, 1983; Brook, 1985;
misuse, while most pneumonia
of elderly institutionalised patients. The
low aggregate male cancer mortality (Table
2) is largely explained by a reduced lung
cancer mortality (Mortensen & Juel, 1990;
Newman & Bland, 1991). Female cancer
in both mortality is unexceptional.
tuberculosis are now rare.
Unnatural-cause mortality
Unnatural deaths (ICD—9800—999) were
significantly increased among
and females in all studies (Table 2) that
analysed the cause of death (aggregate SMR
426, 95% CI 402—451), and account for
about 41 % of the total excess mortality of
schizophrenia.
Accidents
The SMR from accidents was twice the rate
in the general population (SMR
CI 196—236), with no significant gender
difference, and accounted for about 12%
of the excess mortality. Mortensen & Juel
(1990) reported that two-thirds of the excess
accidental deaths among older patients were
from falls (SMR 166, 95% CI 138—199),and
the remainder from aspiration (SMR 3153,
95% CI 2196—4385). The absolute mortality
from road traffic accidents is reduced;
deaths were per mile driven is probably increased
(Edlund et a!, 1989). The mortality from
non-motor vehicle accidents is increased
(Weiner & Marvit, 1977; Wood eta!, 1985).
Suicide
Deaths from
Suicide accounted for 12% of all deaths in
this analysis (Table 3) and about 28% of
the excess deaths, and is the largest single
cause of the excess mortality of schizo
phrenia. The SMR was raised in all of
both males these cohorts, with an aggregate value of
838 (95% CI, 784—894), and was signifi
cantly higher among men (956, 95% CI
884—1031), than among women (673,
95% CI 591—763). The true rate is
probably higher, as a quarter of accidental
and undetermined schizophrenic deaths are
probably misclassified suicides (Allebeck et
a!, 1986). Suicide was increased through
out the course of schizophrenia but was
216, 95%
highest in the year following diagnosis
(Mortensen & Juel, 1993). The SMR from
suicide in the first year following diagnosis
has risen over the past decade (Mortensen
& Juel, 1993).
Homicide
Deaths from homicide were significantly
increased among both males and females

Table3 Suicide
mortalityofschizophrenia

AuthorsMaleFemaleTotalObserved

ExpectedSMR(95%Cl)Weiner ExpectedSMR(95%Cl)Observed ExpectedSMR(95%Cl)Observed

& Marvitt, USA (I 977) 3 I 300 (689—

I954)* 0.4 000 (26 I 7 I.4 2 l4 (706—I860)*
Copas & Robin, UK (1982) 86 14.1 610 (488_746)* 30 0 300 (202@4l70)* I 16 24.l 48l (398—573)
Pokorny, USA (I 983) I9 0.9 I980 ( I268—3
I 67)* I9 0.9 I980 ( I268—3
I 67)*
Allebeck,Sweden(l986) l8 1.8 l000(59l_l5l5)* IS 0.9 l660(930@26l7)* 33 2.7 l230(84l_l675)*
Nyman & Johnsson, Sweden 9 0.3 3000 (I 360@S280)* I 0. I I000 (4-3920) I0 0.4 2500 (I I90@4290)*
( I986)
Black, USA(1988) 12 0.4 3000(l542_4937)* 6 0.1 5450(2l59—3465) 18 0.5 3600(2l30@S4S5)*
Zilberetal, Israel (1989) IS 4.7 320 (l78—50l)
Mortensen & Juel, Denmark 37 27.4 I35 (95—
I82) I9 IS I36 (76—
I90) 56 42.4 I36 (I 00—
I70)
(1990)
Andersonetal,UK (1991) S 0.3 l950(526_3448)* 2 0.15 l280(l040@382l)* 7 0.4 l660(693_3286)*
Newman&Bland,Canada 81 3.9 2076(1649_2543)* 16 .0 l600(9l2—33S4) 97 4.9 209l (1602_2393)*
(1991)
Mortensen&Juel,Denmark
2073(l897_2258)*Total650 370 17.9I 2067(186l_2283)*4 138 6.6I 2091 (1757_2454)*I 508 24.5I
( I993)I

106.9838(784—894)Variation 68.09S6(884—lO3I)231 34.3673(59l_763)*896

from expected value signifcant at 5% level.

505
(SMR 733, 95% CI 363—1230), but ac
counted for only 1% of the excess mortality.
Undetermined deaths
Death is coded as undetermined if there is
insufficient evidence to decide the cause.
The mortality from undetermined causes
was greatly increased (Allebeck & Wistedt,
1986) with an SMR of 1430 (95% CI 960—
2130).
DISCUSSION
Limitations and errors of this
meta-analysis
Meta-analysis weights information by the
size of the cohort from which it was derived.
It has the potential to produce significant
results by aggregating individually non
significant studies. However, important dif
ferences between studies may be obscured,
in this case differences in diagnostic criteria,
hospital discharge patterns and death cciii
fication.
The most accurate form of meta
analysis involves the review and analysis
of individua! patient data, and can include
unpublished series and data on patients
excluded from published analysis (Stewart
& Parmar, 1993). This paper describesa
meta-analysis of the literature. Literature
analysis may be affected by publication
bias, in this case a preference for studies
reporting variation from expected mortal
ity. Small cohort studies (e.g. Wilkinson,
1982; Lesage et a!, 1990) were excluded to
reduce the possibility of this. Funnel
analysis (Dickersin & Berlin, 1992) sug
gests that publication bias was not an
important source of error. Studies of less
than two years' duration were excluded
from the meta-analysis to reduce bias from
the clustering of suicide around contact
with psychiatric services (Caldwell &
Gottesman, 1990).
Cohorts with a high drop-out rate (e.g.
Saku et a!, 1995) were excluded as mortality
is higher among subjects lost to follow-up
than among those who are traced (Sims,
1973). Some studies did not measure com
pleteness of follow-up as they only linked
case registers to death certificates, hence
subjects without death certificates were
assumed to be alive. These studies (Babigian
& Odoroff, 1969; Eastwood et a!, 1982;
Haugland et a!, 1983; Herrman et a!, 1983;
Allebeck & Wistedt, 1986; Black, 1988;
Hassall et a!, 1988; Zilber et a!, 1989;
Newman & Bland, 1991) will have under
506
estimated mortality, but were included in
the meta-analysis to avoid giving undue
weight to in-patient cohorts.
Analysis of heterogeneity
The results of the studies included in the
meta-analysis were significantly heteroge
neous (x265.9, d.f.=17, P<0.001). Ana
lysis of the data by phase of illness of the
cohort suggested that first-episode schizo
phrenia (Eastwood et a!, 1982; Mortensen
& Juel, 1993) had a SMR of 332 (95% CI
312—351) and chronic schizophrenia (Giel
et a!, 1978; Brook, 1985; Mortensen &
Juel, 1990) a SMR of 121 (95% CI 118—
124). Cohorts of subjects at varying points
in their illness had an SMR of 193 (95% CI
187—206). Division of the cohorts into
three groups in this way, led to a sub
stantial fall in hete,rogeneity (x2=6.9@
d.f.=1S, P=0.S) and suggeststhat phase
of illness explains a large part of the
original heterogeneity.
First-episode cohort studies provide the
most accurate estimate of the excess mor
tality of schizophrenia, as other cohorts will
contain subjects who have already survived
the period of greatest excess mortality. Even
first-episode studies will underestimate the
true mortality, as a number of people with
schizophrenia die, for example from suicide,
before being recognised by the mental health
services. The aggregate figure from the two
first-episode studies (SMR 332, 95% CI
312—351)is slightly high, as the SMR would
probably have fallen if the cohorts had been
followed for longer (Munk-Jorgensen &
Mortensen, 1992), but is the best figure
which can currently be placed on the excess
mortality of schizophrenia.
Comparison with the mortality of
other diseases
The SMR of schizophrenia is comparable
with that of chronic physical diseases such
as diabetes (SMR 2.2; Riley eta!, 1995). The
mortality is similar to that of affective illness
(Eastwood et a!, 1982; Wood et a!, 1985;
Zilber et a!, 1989; Amaddeo et al, 1995;
Baxter, 1996), which has a similar large
excess of suicide deaths, but is lower than
that of organic mental disease (Wood et a!,
1985; Hassall et a!, 1988; Zilber et a!,
1989).
Monitoring trends in mortality
We do not know whether or not the
mortality of schizophrenia was affected by
de-institutionalisation. The aggregate SMR
of modern cohorts with schizophrenia is
lower than the SMRs of asylum cohorts
(Malzburg, 1934; ødegârd,1936; Alström,
1942), but the effects of confounding van
ables and selection bias means that we
cannot be sure whether or not this is a real
change. We do not know how many
premature deaths occur in schizophrenia in
the UK each year, or whether the mortality
is different in other Western countries, and
have no reliable way of measuring whether
mortality is rising or falling.
This is surely unacceptable, as mortality
is a fundamental measure of outcome. The
mortality of mental illness should be mon
itored nationally to measure the impact of
national policy changes, and locally to
measure the effect of local interventions
and the performance of individual services.
Measurement should be diagnosis-specific,
as case mix introduces a further source of
contamination, and tracing should be corn
plete. Cohorts should be matched for
potential confounding variables. Local mea
surement of schizophrenia mortality is
feasible in the UK (Hassall et a!, 1988;
Baxter, 1996). However, reliable national
measurement is not yet possible as there is
no mechanism, such as a national psychi
atnic case register, from which to identify
representative cohorts.
Specific causes of death
Suicide is the single largest cause of pre
mature death in schizophrenia, and hence
the area where there is the greatest potential
to reduce mortality. Many factors associated
with suicide in schizophrenia are known,
but attempts to identify high-risk patients
have so far produced too many false positive
results to be clinically useful (Caldwell &
Gottesman, 1990). Further work in this area
should be a priority, as the rate of suicide in
schizophrenia appears to be increasing
(Mortensen & Juel, 1993). Accidental
deaths are also significantly increased, and
could probably be reduced by closer medical
and nursing supervision.
The excess natural mortality of schizo
phrenia also needs to be addressed. Much of
the variation is probably determined by
factors which affect mortality in the general
population. There is no explicit link between
schizophrenia mortality and poverty, though
Baxter (1996) found that about 20% of the
excess mortality in an undifferentiated
population with mental illness disappeared
when the rates were adjusted to take
account of social class. Other possible
culprits include cigarettes and alcohol (Mor
tensen & Juel, 1993) and unhealthy diet and
lack of exercise.
The relationship between smoking and
schizophrenia mortality is particularly inter
esting. Cancer mortality (Saku et a!, 1995)
and incidence (Dupont et a!, 1986; Morten
sen, 1989) is reduced at a number of sites.
Some of this may be chance association, or
due to known risk factors such as the
association between sexual activity and
cervical cancer or low fertility and increased
breast cancer. There are no specific studies of
the mortality of smokers with schizophrenia.
However, smoking provides a plausible
explanation of the raised mortality from
respiratory disease. The reduced male mor
tality from lung cancer is therefore very
surprising.
The impact of psychotropic drugs on the
mortality of schizophrenia is unknown.
Mortensen & Juel (1990) found a raised
SMR (180, 95% CI 161—199)among older
patients from causes such as falls, aspiration
and diabetes, which were possibly related to
drug side-effects. Some of the variation in
cerebrovascular and cardiovascular mortal
ity (Table 2) may be due to the effects of
psychotropic drugs, while Mortensen (1989)
suggests that the reduced cancer incidence
may be secondary to their effects on
prolactin secretion.
Avoidable natural deaths
Kraepelin (1919) and others have suggested
that reluctance to seek medical attention
and poor compliance with treatment might
contribute to the mortality of schizophre
nia. Mortensen & Juel (1990, 1993) found
that the mortality from ‘¿treatable'condi
tions (Rutstein et a!, 1976), was signifi
cantly increased (SMR 135, 95% CI 109—
163). It is unclear whether psychiatrists or
general practitioners are best equipped to
treat physical disease in people with severe
mental illness. Until this is decided, respon
sibility for the physical care of each patient
should be explicitly allocated and accepted,
and all doctors should be alert for signs of
physical disease.
Further research
Further research is needed to tease out the
factors which cause the excess mortality of
schizophrenia and to provide a sound basis
for intervention studies. Further large pro
spective cohort studies are needed to exam
inc the mortality from specific causes and
the contribution of cigarette smoking and
social factors. Individual follow-up studies
are needed to identify specific deficiencies in
treatment and to suggest changes in clinical
practice.
Health education programmes which
have been effective in the general population
should be evaluated in cohorts with schizo
phrenia. Such interventions may have to be
adapted to fit the needs of people with
schizophrenia, and should have explicit
protocols and goals in order that benefits
and costs can be established.
ACKNOWLEDGEMENTS
Thanks to Dr Brian Barraclough and Clare Harris for
their support and advice in the preparation
work.
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