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Factors Influencing Risk of Premature Mortality in Community Cases of Depression: A Meta-Analytic Review


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Background. Depressive disorders are associated with substantial risk of premature mortality. A number of factors may contribute to reported risk estimates, making it difficult to determine actual risk of excess mortality in community cases of depression. The aim of this study is to conduct a systematic review and meta-analysis of excess mortality in population-based studies of clinically defined depression. Methods. Population-based studies reporting all-cause mortality associated with a clinically defined depressive disorder were included in the systematic review. Estimates of relative risk for excess mortality in population-representative cases of clinical depressive disorders were extracted. A meta-analysis was conducted using Stata to pool estimates of excess mortality and identify sources of heterogeneity within the data. Results. Twenty-one studies reporting risk of excess mortality in clinical depression were identified. A significantly higher risk of mortality was found for major depression (RR 1.92 95% CI 1.65–2.23), but no significant difference was found for dysthymia (RR 1.37 95% CI 0.93–2.00). Relative risk of excess mortality was not significantly different following the adjustment of reported risk estimates. Conclusion. A mortality gradient was identified with increasing severity of clinical depression. Recognition of depressive symptoms in general practice and appropriate referral for evidence-based treatment may help improve outcomes, particularly in patients with comorbid physical disorders.
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Hindawi Publishing Corporation
Epidemiology Research International
Volume 2011, Article ID 832945, 12 pages
Review Article
Factors Influencing Risk of Premature Mortality in
Community Cases of Depression: A Meta-Analytic Review
Amanda J. Baxter,1, 2 Andrew Page,1and Harvey A. Whiteford1, 2
1School of Population Health, The University of Queensland, QLD 4006, Australia
2Policy and Evaluation Group, Queensland Centre for Mental Health Research, QLD 4074, Australia
Correspondence should be addressed to Amanda J. Baxter, amanda
Received 14 December 2010; Revised 15 February 2011; Accepted 15 March 2011
Academic Editor: Susana Sans Menendez
Copyright © 2011 Amanda J. Baxter et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
Background. Depressive disorders are associated with substantial risk of premature mortality. A number of factors may contribute
to reported risk estimates, making it dicult to determine actual risk of excess mortality in community cases of depression. The
aim of this study is to conduct a systematic review and meta-analysis of excess mortality in population-based studies of clinically
defined depression. Methods. Population-based studies reporting all-cause mortality associated with a clinically defined depressive
disorder were included in the systematic review. Estimates of relative risk for excess mortality in population-representative cases
of clinical depressive disorders were extracted. A meta-analysis was conducted using Stata to pool estimates of excess mortality
and identify sources of heterogeneity within the data. Results. Twenty-one studies reporting risk of excess mortality in clinical
depression were identified. A significantly higher risk of mortality was found for major depression (RR 1.92 95% CI 1.65–2.23),
but no significant dierence was found for dysthymia (RR 1.37 95% CI 0.93–2.00). Relative risk of excess mortality was not
significantly dierent following the adjustment of reported risk estimates. Conclusion. A mortality gradient was identified with
increasing severity of clinical depression. Recognition of depressive symptoms in general practice and appropriate referral for
evidence-based treatment may help improve outcomes, particularly in patients with comorbid physical disorders.
1. Introduction
Depressive disorders make a substantial contribution to
the global burden of disease [13]. Their contribution to
disease burden is largely attributed to the high prevalence
of, and disability caused by, depression [1]. Contribution
to disease burden of premature mortality in individuals
with depression is less well studied, with the exception of
suicide and more recently coronary heart disease. Depressive
disorders are a well-recognized risk factor for suicide [4], and
increased treatment of depression has been associated with a
decrease in suicide rates [5,6].
Increased risk of excess all-cause mortality has previously
been shown in psychiatric inpatients [79]. Excess mortality
in psychiatric inpatients has been associated with conditions
such as gastrointestinal infection and respiratory disease, and
previously attributed to conditions within hospitals or asy-
lums [10], although the introduction of modern psychiatric
treatments and shorter duration of stay in hospitals has
improved mortality outcomes for individuals hospitalized
with depression [11].
Deinstitutionalization of individuals with chronic mental
disorders has been continuing over the past 50 years [12],
with only a small proportion of those with depression
now hospitalized, and then for short periods. Due to
both increased reliance on community care [13]andlow
treatment-seeking rates for depression [14], those hospi-
talised are more likely to be presenting with severe symp-
tomatology and not representative of depressive disorder in
the community. Despite improvements in the treatment of
depression, a growing body of literature suggests that persons
with depressive disorder in the community still experience
excess mortality compared to those without depression.
Two pathways have been proposed leading to increased
mortality in depression. The first is increased tendency
for adverse health behaviours [15]. Depression has been
2Epidemiology Research International
associated with greater likelihood of smoking [16,17],
alcohol, and drug abuse [1820] and more sedentary
lifestyles [21]. In those with chronic diseases, depression is
associated with noncompliance with medical treatment [22
24] and worse health outcomes including increased deaths
[25]. The WHO World Health Survey (WHS) collected
data on mental disorders and a range of physical disorders
in 60 countries [26]. Respondents with depression and
one or more comorbid physical disorders had the worst
overall health states of all the disease states, including either
combined physical disorders or depression alone.
suggesting a biological progression [27], including the
dysfunction of inflammatory response [28]. Depression has
been described as an independent risk factor for both
coronary heart disease [29]andanumberofcancers[27]. It
has also been independently associated with increased levels
of inflammatory markers [30,31]. While this finding is not
always consistent, it may be that methodological dierences
between studies are having a confounding eect on the
relationship. For example, one study where an association
was not found reported depression as identified through the
General Health Questionnaire (GHQ) [32]. This measure is
likely to reflect subthreshold depressive symptomatology, as
well as clinical depression. This highlights the importance
of a consistent definition of depression when looking at
associations with adverse health outcomes. Inflammation has
also been implicated in the pathogenesis of a range of chronic
diseases including diabetes [33], atherosclerosis, and related
high mortality diseases such as coronary artery disease [34].
Thus depression is thought to be a contributing factor to the
development of these diseases and also associated with an
increased risk of mortality in those with comorbid physical
Previous systematic reviews have shown increased risk
of mortality in people suering from depression [3540],
especially in males and in those with severe depression [35].
However, previous estimates of mortality combined clinical
and community samples [35,37] and nonclinical definitions
of depression [36,38].
Three previous meta-analyses focusing on all-cause
mortality in community-based studies of depression [36,
38,40] found higher mortality in those with depressive
disorders compared to those without. Pooled eect sizes
ranged from 1.56 to 1.81 [36,38,40]. In two of these analyses
[36,38], depression was variably defined, based on both
clinically defined depression (i.e., meeting internationally
recognized diagnostic criteria such as DSM [41]orICD
[42]) and subclinical depression or depressive symptoms
ascertained through symptom scales such as the General
Health Survey or CES-D. If severity is a mediating factor, the
inclusion of subclinical cases of depression may result in an
underestimate of excess mortality for depression.
Synthesis of the current evidence linking clinical depres-
sion with premature death, along with the identification of
potential modifiers, may be relevant in informing public
health policy, and clinical practice aimed at reducing mortal-
ity. The aim of this paper and meta-analysis is to examine the
risk of premature mortality in clinically defined depression
and identify factors which may influence reported mortality
2. Methods
2.1. Data sources. A systematic search was conducted to
identify papers reporting mortality for population-based
studies of depressive disorders. The methodology follows
the recommendations by the Meta-analysis of Observational
Studies in Epidemiology (MOOSE) Group [43]. A broad
search string was developed with the assistance of a research
librarian to search electronic databases (Medline, Embase,
Psychinfo, Scopus and Google Scholar). Broad search terms
were employed as well as key words for specific mental
disorders, including depression, depending on database
requirements. Searches were limited to human participants
and individual-level analytic studies (either cohort or case-
control studies). No limitations were set on language of
publication. Article titles were scanned for relevance, and
abstracts of potential papers were read to identify duplicates,
further reduced the list according to predetermined criteria.
Prospective cohort or case-control studies were sought
reporting excess all-cause mortality. Studies were excluded if
they were not observational and analytic (e.g.; case studies
or treatment trials), did not report relative associations
between exposure and outcome (or provided insucent data
to calculate eect size) or did not contain primary data (such
as review articles). If multiple papers were identified from a
single study, the most recent or relevant article was included.
The full text of all potentially relevant papers was reviewed.
Citations from identified primary data papers, reviews, and
monographs were examined to locate additional sources of
Depressive disorders were defined as those disorders
meeting ICD or DSM diagnostic criteria (including where
survey tools map to these criteria) for depressive disorders.
Only studies based on samples from the general population
were included in analyses. Studies based on occupational
groups (e.g., veterans) or conducted in clinical settings, or
inpatient populations, were excluded to reduce the eects
of potential confounders that may be associated with both
occurrence of depression and increased risk of mortality, and
in the case of inpatient samples, where cases were more likely
to be severe [44].
A summary of the studies meeting the review’s inclusion
criteria is shown in Ta b l e 2 . Studies meeting inclusion
criteria included samples identified with depressive disorders
between 1952 and 2001 in Western Europe, North America,
Australia, and Africa.
2.2. Data Abstraction. Data extracted from papers included
study design, sample ascertainment, diagnostic instrument,
geographic location, adjustment for confounding, and loss to
followup. Design factors rather than aggregate quality scores
are perhaps more important in interpreting heterogeneity
across studies [43], hence a range of variables reflecting study
methodology and reporting were also abstracted. Other
Epidemiology Research International 3
variables included sample descriptors (e.g., age, gender,
characteristics) and measurement parameters (e.g., type of
estimate, period of follow-up, error).
Adjusted estimates of relative risk and confidence inter-
vals were extracted where reported. Estimates of relative risk
included odds ratios, hazard rate ratios, and standardized
mortality ratios. Numbers of exposed (depressed) and
nonexposed (controls) were extracted, as well as numbers
of deaths in each group. Where an adjusted eect size was
not reported, or an adjusted eect size was reported without
uncertainty, crude relative risk and confidence intervals were
calculated using numbers of exposed and nonexposed and
relative numbers of deaths in each group.
2.3. Statistical Methods. Meta-analyses were conducted to
estimate pooled relative risk for all-cause mortality. Analyses
we re car ried o ut on S TATA-I C 1 0 sof twa re. D u e to t h e hig h
level of heterogeneity we used the metan function which
specifies a random-eects model using the DerSimonian and
Laird method [45]. I2statistics were calculated to determine
variation attributable to heterogeneity with a value of 0%
indicating no observable heterogeneity between studies and
larger values indicating increasing heterogeneity [46,47].
Egger’s regression test for small study eects was conducted
using the metabias function.
A stepwise metaregression was carried out to explore the
degree to which covariates explained the degree of between-
study variability [48]. A number of covariates identified
through univariate analysis comprised the original regression
model. These included follow-up period, gender, age range
and definition of depression (major depression, dysthymia
or unspecified depression). The meta-regression was carried
out i n STATA usi ng th e metareg command which reported
an adjusted R2statistic. Covariates were then excluded one at
a time until the model reflected the greatest between-study
3. Results
Risk statistics for all-cause mortality were identified for
twenty studies (see Figure 1). Data were reported for 153,965
participants with 51% from Western Europe, 48% from
North America, and <1% each from Australasia and Africa.
After reviewing the articles and excluding duplicated sam-
ples, twenty studies from twenty-one papers provided an
estimate of risk for all-cause mortality in community samples
[4969]. The estimates were based on an estimated total of
13,090 deaths with a median follow-up period of 4.4 years
(range 1–17 years).
Excess mortality was significantly higher in those with
clinically defined depression compared to those without
depression (RR 1.67, 95% CI 1.48–1.90). In addition, a
dose-response eect was observed for pooled estimates when
depressive disorders were stratified by severity (Figure 2).
Relative risk for premature mortality in major depressive
disorder was highest with a RR of 1.92 (95% CI 1.65–2.23)
compared to studies reporting unspecified depression (RR
1.46 95% CI 1.22–1.76) and dysthymia (RR 1.37 95% CI
0.93–2.00). Heterogeneity between studies was reduced when
the definition was narrowed to include only major depressive
disorder (I2=38.2%P=.066).
Males with depression had a 78% greater risk of dying
prematurely compared to controls and females with depres-
sion were at 63% greater risk (see Ta b le 1). Ad hoc sensitivity
analyses were conducted to explore the relationship between
risk of excess mortality and various covariates such as
age range, study follow-up period, definition of depression
(MDD, unspecified depression, and dysthymia), and type of
estimate (RR, OR, SMR, HRR).
Seven studies reported risk of excess mortality for adults
in a broad age range [49,52,6265,68] and thirteen reported
on only older adults (60 years and over) [50,51,5361,66,
67,69]. No studies were identified that reported risk for
children/adolescents or that stratified risk by age. Tabl e 1
shows that risk of excess mortality was slightly higher for
samples comprising all adults compared to those only in
the older age group (RR 1.85 and 1.59, resp.). A higher risk
of excess mortality was also observed in studies that had a
follow-up period of less than five years (RR 1.91) compared
to those with follow-up periods of five years or greater (RR
Approximately one quarter of studies identified reported
risk estimates adjusted for age and/or sex and slightly
fewer reported estimates adjusted for additional factors such
as demographic (marital status, education, or household
income), behavioral and health risk factors (smoking, alco-
hol consumption, or presence of other chronic disease). No
substantial dierences were found between the pooled eect
sizes for studies that adjusted for age and/or sex (RR 1.85),
those adjusted for additional risk factors (RR 1.77), and those
that reported unadjusted eect size (RR 1.59).
A stepwise metaregression was carried out to identify a
model explaining the greatest proportion of between-study
variance. The final model, explaining 80.4% of between study
variability, included follow-up period, gender, and definition
of depression. Residual variation due to heterogeneity (I2res)
was reduced from 69.1% to 17.2%.
A funnel plot was generated with a fitted regression line
from the standard regression (Egger) test for presence of
asymmetry (Figure 3). The plot of risk for excess mortality
is skewed and asymmetric with evidence of smaller studies
showing associations that dier systematically from larger
studies (Egger’s test P<.02). It is possible that small studies
showing little risk for excess mortality remain unpublished.
Alternatively small studies may overestimate risk compared
to larger studies.
4. Discussion
The present study found significantly higher risk of excess
mortality in community cases of depression compared to
those without depression. Previous analyses have reported
eect sizes ranging between 1.56 and 1.81 [36,38,40]. The
present review highlights the increased risk of premature
mortality with greater severity of symptoms. While major
depression was associated with almost twice the risk of
4Epidemiology Research International
Tab le 1: Pooled relative risk of excess all-cause mortality in community cases of depressive disorders.
No depressive disorder
(deaths/Total) RR 95% CI I2
Overall 21 1,167/6,687 11,650/151,721 1.67 1.48–1.90 69.10%
Males and females 16 982/5,620 9,291/90,765 1.66 1.42–1.94 75.10%
Males 5 82/377 1,263/28,669 1.78 1.27–2.51 61.60%
Females 5 103/690 1,096/32,287 1.63 1.32–2.02 14.10%
Disorder type#
Major depression 12 345/2,284 5,986/79,615 1.92 1.65–2.23 38.20%
Unspecified depressive disorders 8 738/4,183 4,277/67,797 1.46 1.22–1.76 70.00%
Dysthymic disorder 2 84/220 1,387/4,309 1.37 0.93–2.00 76.60%
Age range
Adults (all ages) 8 479/4,411 6,656/130,033 1.85 1.46–2.35 73.10%
Older adults (60+) 13 688/2,276 4,994/21,688 1.59 1.37–1.83 60.50%
Followup period
Less than 5 years 13 651/5,631 6,651/134,016 1.91 1.70–2.14 15.90%
5 years or more 8 516/1,326 5,089/17,705 1.41 1.23–1.62 55.30%
Adjustment factors
Unadjusted 10 462/1,151 5,115/17,996 1.59 1.25–2.01 57.50%
Age and/or sex 6 509/3,913 4,768/74,453 1.85 1.60–2.15 28.90%
Age and/or sex and other factors 5 196/1,623 1,767/59,272 1.77 1.32–2.38 61.70%
RR: relative risk; CI: confidence intervals.
I2represents as a percentage of the variation attributable to heterogeneity between studies.
#number of studies do not add up to 21 as 5 studies reported estimates for males and females, and 1 study reported estimates for both major depression and
premature mortality, no significant risk was found in
association with dysthymia. Inclusion criteria for this meta-
analysis were restricted to diagnostic instruments with high
specificity for clinically significant depression. Subthreshold
disorders are likely to be associated with lower risk of excess
mortality. Inclusion of subthreshold depression or depressive
symptoms may bias pooled estimates toward the null.
The current review found a pooled estimate for excess
mortality higher than that reported by Harris and Barra-
clough [35] for major depression (SMR =1.36). However,
due to data availability at that time, the earlier review
included papers published prior to DSM diagnostic criteria,
with diagnoses such as melancholia, unipolar depression,
primary depressive illness, and late onset primary clear-cut
depression. As this review has demonstrated, definition of
risk factor is an important source of variability. Greater
consistency of definition for clinical depression provided
a more homogenous representation of mortality risk in
depressed cases according to modern DSM/ICD diagnostic
The present study found slightly higher risk in studies of
all ages compared to older adult samples, and the study with
the youngest age group (15–49 years) reported the highest
risk of excess mortality (RR 3.55 95% CI 1.97–6.39). One
other review has examined mortality by age group and found
increased risk for adult samples over age 40, compared to
all adults (adults 18 years) or older adults (65 years)
[36]. The nonlinear trend by age reported in this review
may reflect the heterogeneity of age groupings within the
data available. One hypothesis for the reduced risk in older
age groups is that it reflects survivor bias within depressed
samples. It is possible that people with depressive disorders
are less likely to survive into older age and hence the risk of
excess mortality is reduced in this age group.
Several possible explanations have been advanced for
the higher mortality risk associated with depression. First,
depression and physical disorders co-occur and frequently
complicate each other [39]. Co-occurring disorders may
mask the presence of depression, and depression in com-
bination with physical disorders results in poorer health
outcomes [26,39]. Data from the recent World Mental
Health Survey show that individuals are more likely to seek
treatment for physical disorders than for mental disorders
[14]. Other studies have found that even though individ-
uals may not seek treatment specifically for their mental
disorders, they often seek treatment for coexisting physical
health problems [72]. Although 5.4% of a patient sample
attending a General Practice [GP] sought treatment for
mental disorders, prevalence of clinical or subclinical criteria
for a mental disorder within the GP attending population
was over 40% [72]. Individuals may be accessing health
care but are not reporting symptoms of mental disorder,
or medical professionals are not recognizing symptoms in
persons with coexisting physical disorders. It is likely that
Epidemiology Research International 5
Tab le 2: Studies reporting risk of all-cause excess mortality in community cases of depressive disorder.
Source Disorder Country Study
period Sample Survey
Gender Estimate
type Eect Size 95% CI Factors
adjusted for
Murphy et
al. [64]MDD USA 1952–1952 Gen pop
18+ yrs Structured iv 17 M, F Unadj RR 1.84, 2.13 0.9–3.73,
et al. [59]Unspecified
depression UK 1982–1986 Gen pop
65+ yrs GSM–CATEGO 3 M&F Unadj RR 1.74 1.03–2.94
Jorm et al.
[54]MDD Australia 1982–1983 Gen pop
70+ yrs GMS + MMSE 5 M&F Unadj RR 1.5 1.06–2.11
Aromaa et
al. [68]Unspecified
depression Finland 1978–1981 Gen pop
40–64 PSE–CATEGO 6.6 M&F Unadj RR 2 1.35–2.96
Bruce et al.
Dysthymia USA 1980–1980 Gen pop
40+ yrs DIS (DSM3) 9 M, F Unadj RR 1.16, 0.97 0.86–1.57,
Kouzis et
al. [62]MDD USA 1980–1980 Gen pop
18+ yrs DIS 1 M&F OR 2.6 1.1–6.0
Age, sex,
and Lane
depression Australia 1985–1987 Gen pop
65+ yrs
Clinical iv
(DSM3R) 2 M&F Unadj RR 2.23 0.8–6.2
depression Norway 1984–1987 Gen pop
75+ yrs
Clinical iv
(DSM3R) 3 M&F OR 1.9 1.0–3.6 Age
et al. [55]Unspecified
depression Australia 1990–1994 Gen pop
70+ yrs CIE 3.6 M&F Unadj RR 1.26 0.69–2.32
Pulska et
al. [58]
depression Finland 1984–1985 Gen pop
65+ yrs
Clinical iv
(DSM3) 5.9 M, F RR 1.21 0.94–2.06,
Age, sex,
status, low
Zheng et
al. [63]MDD USA 1989–1989 Gen pop
(white) 25+
(71% males and
79% females
report diagnosis
by physician)
2.5 M,F HRR 3.1,1.7 2.0–4.9,
marital status
Pulska et
al. [66,67]MDD Finland 1984-1985 Gen pop
65+ yrs
Clinical iv
(DSM3) 5.9 M, F RR 1.88, 2.06 1.11–3.19,
1.25–3.39 Unadj RR
6Epidemiology Research International
Tab le 2: Continued.
Source Disorder Country Study
period Sample Survey
Gender Estimate
type Eect Size 95% CI Factors
adjusted for
Pulska et
al. [66,67]Dysthymia Finland 1989-1990 Gen pop
65+ yrs
Clinical iv
(DSM3) 6 M, F RR 1.52, 1.77 1.04–2.21,
1.30–2.40 Unadj RR
Penninx et
al. [61]MDD Netherlands 1992–1997 Gen pop
55–85 DIS 4.2 M&F RR 2.32 1.38–3.89 Age, sex
Vinkers et
al. [69]MDD Netherlands 1997–1999 Gen pop
85+ yrs
GDS–15 (4)
MMSE (>18) 3.2 M&F RR 2.07 1.35–3.17
Sex, smoking,
alcohol, and
other chronic
et al. [50]MDD England 1996–1998 Gen pop
75+ GDS–15 3 M&F HR 1.79 1.5–2.13 Age
et al. [56]MDD Sweden 2000–2002 Gen pop
Clinical iv
(DSM4) 1 M&F Unadj RR 2.15 1.16–3.97
Gallo et al.
[51]MDD USA 2001–2001
Care 60+
SCAN 2 M&F OR 1.78 1.06–2.99
Age, sex,
and smoking
Mogga et
al. [52]MDD Ethiopia 1998–2001 Gen pop
15–49 CIDI 3 M&F SMR 3.55 1.97–6.39 Age, sex
et al. [49]Unspecified
depression Norway 1995–1997 Gen pop
19+ yrs HADS 4.4 M&F OR 1.68 1.46–1.92 Age, sex
et al. [57]Unspecified
depression Netherlands 1990–2000 Gen pop
65–84 GMS–AGECAT 10 M&F Unadj RR 1.18 1.08–1.28
MDD: major depressive disorder;
RR: Relative risk; Unadj RR: Unadjusted relative risk; OR: Odds ratio; SMR: Standardised mortality ratio; HRR: Hazard Risk Ratio;
M&F: person; M: Males; F: Females.
Epidemiology Research International 7
Records identified through database searching
Additional records identified
through manual search
Records after duplicates removed
Full-text articles assessed for eligibility
Studies included in quantitative analysis
Records excluded after abstract/title search (pre-
morbid sample, clinical trial, inpatient sample)
1Not community cases =study featured clinical samples or members of a treatment group only
2Risk estimate not reported =reported number of exposed who died but not the denominator therefore not allowing mortalit
rate to be calculated, or did not report deaths in controls
1Not clinically defined depression =study used a scale not validated against dsm or icd criteria therefore reports on depressive
symptomatology only
Not community cases (86)1, sample not
representative (162), all =cause mortality
not reported (76)2, risk estimate not reported
(118), not clinically defined depression (90)3,
study overlap (2)
Figure 1: Flowchart showing results of systematic review.
individuals with multiple health problems are not receiving
appropriate treatment for a comorbid mental disorder
[39]. Underdiagnosis is a concern as depression has been
associated with poorer health outcomes including higher
fatality rates in those with coronary heart disease [73,74],
cancer [75], and stroke [71].
Persons suering depression are also more likely to
neglect their health and show poor adherence to prescribed
medication regimens [15,2224]. The causal direction of
these relationships is a focus of current research. Possible
associations include depression as a result of lifestyle factors,
depression leading to lifestyle factors or both depression
and lifestyle factors resulting from other independent factors
[76]. Improvement of diagnosis and treatment of comorbid
physical and mental health problems in primary care may
reduce mortality in these groups.
A shorter followup period was associated with increased
risk of excess mortality compared to longer follow-up
periods. Two of the studies with shorter follow-up period
included exposure measures of period prevalence such past-
year [52]andlifetime[63] rather than current preva-
lence. This finding is unexpected as period prevalent cases,
which include those without the current disorder, would
presumably be less likely to neglect their health and have
better adherence to medication at the time of the study
baseline [15] which may be expected to show lower relative
mortality. Possible recall bias in measures of period and
lifetime prevalence may result in misclassification and reduce
relative dierences in mortality if nondierential. However,
insucient data were available to look at the association
between exposure measure and eect size. The eect of
exposure measure deserves further exploration, particularly
the possible interaction with follow-up period and age group.
The main strength of this study relates to the inclusion
criteria which ensured relatively consistent diagnosis of
depressive disorder, limited to population-based studies.
Studies were included where estimates for clinically defined
depression (depression meeting DSM or ICD diagnos-
tic criteria) were reported while broader mental disorder
categories of aective disorders and mood disorder were
excluded. Dimensional measures of symptomatology and
psychological distress were also excluded. Inclusion of sub-
clinical samples may reduce the risk of excess mortality as
severity of depressive symptoms is related to higher rates
8Epidemiology Research International
RR = relative risk; CI = confidence interval
represents as a percentage the variation attributable to heterogeneity between studies
Snowdon et al., 1995
Pulska et al., 1998
Pulska et al., 1997
Pulska et al., 1998
Zheng et al., 1997
Mogga et al., 2006
Engedal, 1996
Mykletun et al., 2009
Aromaa et al., 1994
Murphy et al., 1987
Davidson et al., 1988
Schoevers et al., 2009
Murphy et al., 1987
Zheng et al., 1997
Bergdahl et al., 2005
Bruce et al.,1994
Penninx et al., 1999
Pulska et al., 1998
Vinkers et al., 2004
Bruce et al.,1994
Kouzis et al., 1995
Gallo et al., 2005
Pulska et al., 1997
Adamson et al., 2005
Jorm et al., 1991
Pulska et al., 1998
Major Depression
Henderson et al., 1997
1.67 (1.48, 1.90)
2.23 (0.80, 6.20)
1.52 (1.04, 2.21)
1.20 (0.85, 1.69)
1.77 (1.30, 2.40)
3.10 (2.00, 4.90)
1.37 (0.93, 2.00)
3.55 (1.97, 6.39)
1.90 (1.00, 3.60)
1.68 (1.46, 1.92)
2.00 (1.35, 2.96)
1.84 (0.90, 3.73)
1.74 (1.03, 2.94)
1.18 (1.08, 1.28)
1.46 (1.22, 1.76)
1.92 (1.65, 2.23)
2.13 (1.01, 4.51)
1.70 (0.90, 3.10)
2.15 (1.16, 3.97)
0.97 (0.74, 1.29)
2.32 (1.38, 3.89)
2.06 (1.25, 3.39)
2.07 (1.35, 3.17)
1.16 (0.86, 1.57)
2.60 (1.10, 6.00)
1.78 (1.06, 2.99)
1.20 (0.94, 2.06)
1.79 (1.50, 2.13)
1.50 (1.06, 2.11)
1.88 (1.11, 3.19)
1.26 (0.69, 2.32)
0.5 1 5 10
Overall (I-squared =69.1%, P=0)
Subtotal (I-squared =76.6%, P=.014)
Subtotal (I-squared =70.0%, P=.001)
Subtotal (I-squared =38.2%, P=.066)
Source RR (95% CI)
Figure 2: Forest plot showing included studies and pooled relative risks of excess all-cause mortality in community cases of depressive
disorders, by diagnostic type.
of suicide and self-harm [77]. Whilst acknowledging that
mental ill health is a continuum rather than dichotomous (as
conceptualized by modern diagnostic standards), it would be
inaccurate to compare outcomes for dierent categories of
risk, for example, the inclusion of studies where the “at risk”
group comprised major depression, minor depression, and
subthreshold depression, compared to studies where the “at
risk” group included only major depression [26,72].
A limitation is the low number of studies focusing
on children or adolescents with depression. It may be
that the inclusion of studies featuring child and adolescent
samples would aect the pooled estimate. More cohort
studies involving young people suering mental disorders are
needed to gain a true picture of the long-term outcome of
depression across the lifespan.
The only information identified for children and adoles-
cents with depression was on clinical or inpatient samples,
or where the focus was on traits and behaviors rather than
clinically significant mental disorders [70,7884]. The lack
of data for long-term followup of community adolescent
cases of depression may be due, at least in part, to lack of
epidemiological studies which screen for mental disorders
in young people. While many countries have carried out
regional or national level epidemiologic surveys of mental
health in adults, few similar surveys have been conducted
for young people. Those studies that have done so have
not yet reported long-term outcomes such as mortality
[85,86]. Considering the consistency of the relationship
between early mortality and depression, and the link between
depression and serious physical disorders, should be given to
Epidemiology Research International 9
Standard error of log RR
10 1 2
Log relative risk
Funnel plot with pseudo 95% confidence limits
Figure 3: Funnel plot, using data from 21 studies of excess all-
cause mortality in cases of clinical depression, with log relative risk
displayed on the horizontal axis.
the identification of children and adolescents with depression
as early as possible not only to address their mental health but
also so that physical health can be monitored.
Analysis of heterogeneity in this review found a high
proportion of between-study variance was attributable to
follow-up period, gender, and type of depression. Further
research is required in order to compare and contrast the
risk of premature mortality in mental disorders, other than
depression. Similar analyses are needed across the spectrum
of mental disorders. If conducted along with similar spec-
ifications to this study, the results could be compared to
identify those disorders which present the greatest risk of
premature death.
Our findings support the importance of identification
and treatment of depression in primary care, including
where depression is comorbid with physical disorders. Most
patients with depression are treated in primary care, and here
it should be possible to adequately identify and treat comor-
bid physical disorders. Where depression is being treated in
a mental health service, it is important for clinicians to be
vigilant regarding the physical health status of the patient and
intervene to minimize lifestyle disease risk factors and have
emerging physical disease treated early and eectively.
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... Therefore, indirect costs associated with avoided premature death (e.g. suicide, reduced life expectancy due to mental illness) [82][83][84][85][86] may also be important to consider in future studies in older adult populations. ...
Full-text available
Background Depression and anxiety disorders in older adults are associated with a great burden. Research has shown that less than 50% of adults receive adequate treatment in primary care settings for these disorders. Rare are the studies however assessing adequate treatment in older adults and associated costs from the societal perspective. Given the episodic nature of common mental disorders, this study aims to assess the three-year costs from a restricted societal perspective (including health system and patient perspectives) associated with receipt of minimally adequate treatment for depression and anxiety disorders in older adults consulting in primary care. Methods This primary care cohort study included 358 older adults aged 65 years and older with either a self-reported or physician diagnosis of depression or an anxiety disorder covered under Quebec’s public drug plan. Receipt of minimally adequate treatment was assessed according to Canadian guidelines and relevant reports. Outpatient and inpatient service use, medication costs and physician billing fees were obtained from provincial administrative databases. Unit costs were calculated using provincial financial and activity reports and relevant literature. A propensity score was created to estimate the probability of receiving minimally adequate treatment and the inverse probability was used as a weight in analyses. Generalized linear models, with gamma distribution and log link, were conducted to assess the association between receipt of minimally adequate treatment and costs. Results Overall, receipt of minimally adequate treatment was associated with increased three-year costs averaging $5752, $536, $6266 for the health system, patient and societal perspectives, respectively, compared to those not receiving minimally adequate treatment. From the health system perspective, participants receiving minimally adequate treatment had higher costs related to emergency department (ED) (difference: $457, p = 0.001) and outpatient visits (difference: $620, p < 0.001), inpatient stays (difference: $2564, p = 0.025), drug prescriptions (difference: $1243, p = 0.002) and physician fees (difference: $1224, p < 0.001). From the patient perspective, receipt of minimally adequate treatment was associated with higher costs related to loss of productivity related to ED (difference: $213, p < 0.001) and outpatient visits (difference: $89, p < 0.001). Conclusions Older adults receiving minimally adequate treatment for depression and anxiety disorders incurred higher societal costs reaching $2089 annually compared to older adults not receiving minimally adequate treatment. The main cost drivers were attributable to hospitalizations and prescription drug costs.
... The full-text of 52 references were then scrutinized in detail, of which 19 were excluded with reasons (Additional file 1: Table S1), while 26 references met inclusion criteria (Fig. 1). Overall, 24 references provided quantitative synthesis of evidence [16,19,20,[26][27][28][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67], and 2 references were qualitative systematic reviews [68,69]. This umbrella review included 238 prospective studies and 8 retrospective cohort studies and comprised data from 3,825,380 participants, including 293,073 participants with depression and 282,732 death events, which were grouped in 17 meta-analytic estimates (Additional file 1: Table S2). ...
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Abstract Background Depression is a prevalent and disabling mental disorder that frequently co-occurs with a wide range of chronic conditions. Evidence has suggested that depression could be associated with excess all-cause mortality across different settings and populations, although the causality of these associations remains unclear. Methods We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, PsycINFO, and Embase electronic databases were searched through January 20, 2018. Systematic reviews and meta-analyses that investigated associations of depression and all-cause and cause-specific mortality were selected for the review. The evidence was graded as convincing, highly suggestive, suggestive, or weak based on quantitative criteria that included an assessment of heterogeneity, 95% prediction intervals, small-study effects, and excess significance bias. Results A total of 26 references providing 2 systematic reviews and data for 17 meta-analytic estimates met inclusion criteria (19 of them on all-cause mortality); data from 246 unique studies (N = 3,825,380) were synthesized. All 17 associations had P
We estimated all-cause and cause-specific mortality associated with mental disorder diagnoses using outpatient and inpatient registers from Catalonia. A historical register-based cohort was used, including 516,944 adults diagnosed with psychotic, mood, or anxiety disorders in 2005-2016, and their matched controls. Six psychiatric groups were created using hierarchical rules. Mortality rate ratios (MRRs), calculated with stratified Cox proportional-hazards models adjusted for mental comorbidity, ranged from 2.45 (95%CI = 2.28-2.64) for other non-organic psychoses to 1.11 (95%CI = 1.08-1.15) for anxiety disorders. Higher MRRs were found in males compared to females with non-organic psychoses, other affective and anxiety disorders, and the excess risk of death was higher in younger ages for all the diagnoses except for schizophrenia. Overall, suicide mortality rates were higher for those with mental disorder diagnoses. The highest MRRs due to natural causes were found for metabolic disorders in schizophrenia, infectious diseases in other non-organic psychoses, and respiratory diseases for bipolar, other affective and anxiety disorders. In the most comprehensive study in Southern Europe, excess mortality is observed not only in people with diagnoses of severe mental disorders, but also in those with other mental disorder diagnoses considered less severe, with an important contribution of both natural and unnatural causes.
Objective To assess the association between receipt of minimally adequate treatment (MAT) and mortality in a sample of community primary care older adults with depression and anxiety. Method The present study was conducted among a sample of 358 older adults ( ≥ 65 years old) with depression or an anxiety disorder recruited in primary care practices between 2011 and 2013. Participants agreed to link their health survey and administrative data for the 3 years preceding and following the baseline interview. Depression and anxiety disorders were based on self-reported symptoms aligned with DSM-5 criteria and physician diagnoses (International Classification of Diseases [ICD], 9 th and 10 th revisions). MAT was defined according to Canadian guidelines and include receipt of pharmacotherapy and ≥ 4 medical visits within 3 months or a number of psychotherapy sessions (individual, group, or family) over 12 months (depression: ≥8; anxiety disorders: ≥5 to 7). All-cause 3-year mortality was ascertained from the vital statistics death registry in Québec. Propensity score weighted regression analysis was conducted to assess the association between receipt of MAT and mortality adjusting for individual, clinical, and health system study factors. Results Receipt of MAT was associated with a reduced risk of mortality (hazard ratio [HR]: 0.27; 95% confidence interval [95% CI], 0.12 to 0.62). Individual and clinical factors associated with increased mortality included older age, male sex, being single, low functional status, and increased physical disorders and cognitive functioning. Lifestyle factors associated with reduced and increased mortality included alcohol consumption and smoking, respectively. Health system factors such as perceived adequate number of visits to speak to the doctor about emotional problems and continuity of care were associated with reduced mortality. Conclusion The current study highlights the important tole of primary care physicians in detecting and providing MAT for older adults with depression and anxiety, as this may have an effect on longevity.
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Summary Problem: Depression is a widespread disorder and among the leading causes of disability world-wide. In this article, we perform an umbrella review on the association between depression and excess mortality, cardiovascular disease (CVD), and cardiovascular risk factors. We also provide an overview of mechanisms that explain these associations. Finally, we discuss clinical implica-tions from a general perspective and discuss the potential of physical activity to favorably influ-ence the relationship between depression and premature mortality. Methods: Meta-analyses were identified via PubMed. Only works on unipolar depression were included. Results: The association between depression and excess mortality is a robust epidemiological finding. This association can be attributed to the fact that people with depression are at in-creased risk for CVD and accumulate more cardiovascular risk factors. However, the causal asso-ciations are complex. While depression is associated with incident CVD, depression can also be a consequence of cardiac events. Regular physical activity and higher cardiorespiratory fitness levels mitigate the risk of premature mortality associated with depression. Discussion: More attention should be paid to the poor physical health of psychiatric patients. High priority should be given to the promotion of physical activity and fitness, as they are bene-ficial for both physical and mental health.
Background: Trauma exposure is associated with the development of mood disorders and their phenotypic presentation. Cross-sectional associations between trauma exposure and mood disorders are well documented. Data on the association of trauma with longitudinal mood trajectories are lacking. We investigated the association between trauma exposure and weekly mood trajectories. Method: Mood disorder patients (N = 107; female = 81; mean age = 37.04 years), assessed for trauma exposure at baseline using the Childhood Trauma Questionnaire (CTQ) and Life Events Checklist (LEC), completed weekly telephonic mood assessments using the Quick Inventory of Depressive Symptomatology (QIDS) and Altman Self-Rating Mania scale (ASRM) over a 16 week period commencing at one week post-discharge from hospital. Associations between trauma exposure, severity of mood symptoms and mood trajectories were analysed using Pearson's correlations, LS Mean scores, F-statistics, and RMANOVA. Results: Trauma exposure was persistently associated, albeit with some fluctuation in the strength of the association, with depressive symptomatology. Emotional abuse showed the most persistent association over time. Sexual abuse was minimally associated with depressive symptomatology. The severity of childhood trauma exposure was positively correlated with the severity of depressive symptoms. Lifetime traumatic events were significantly associated with mania scores, however there was no association between childhood trauma exposure and mania symptoms. Conclusion: Identification of both a history of childhood abuse and neglect and lifetime traumatic event exposure is important in the assessment and management of patients with mood disorders, as trauma can exert a persistent impact on depression trajectories and on symptom severity.
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Background: Depression is a family and public health condition that has negative consequences for the victim, family, friends, and society with significant socio-family dysfunction, especially when it is undiagnosed. Aim: The present study was aimed at determining the role of family bio-social variables in depression among ambulatory adult patients in a primary care clinic in the Eastern Nigerian� Materials and Methods: A clinic-based cross-sectional descriptive study was carried out on 400 adult patients in a primary care clinic in Nigeria� Data were collected using Patient Health Questionnaire-9, Family Assessment Device, Multidimensional Scale of Perceived Social Support and Brief Family Relationship Scale� Results: The age of the study participants ranged from 18 to 78 years� There were 40�5% of male and 59�5% of female� The prevalence of depression was 48.5% with the most common pattern being mild depression (32.3%). Depression was significantly associated with unhealthy family functioning (P = 0�002), low-acuity family support (P = 0�039), family with least cohesion (P = 0�044), least expressiveness (P = 0.013), and most conflict (P = 0.013). The most significant predictor of depression was unhealthy family functioning (Odds ratio = 3�14 [1�82-3�77]; P = 0�001)� Depressed patients who had unhealthy family functioning were three times more likely to experience depressive illness compared to their counterparts who were from healthy functional family� Conclusion: Depression occurred among the study participants and was significantly associated with unhealthy family functioning, low family support, least family cohesion and expressiveness and most family conflict. Assessment of family biosocial factors should be part of the reason for encounter during consultation to unravel family variables that positively or negatively influence depression.
Aims: School-based psychological interventions encompass: universal interventions targeting youth in the general population; and indicated interventions targeting youth with subthreshold depression. This study aimed to: (1) examine the population cost-effectiveness of delivering universal and indicated prevention interventions to youth in the population aged 11-17 years via primary and secondary schools in Australia; and (2) compare the comparative cost-effectiveness of delivering these interventions using face-to-face and internet-based delivery mechanisms. Methods: We reviewed literature on the prevention of depression to identify all interventions targeting youth that would be suitable for implementation in Australia and had evidence of efficacy to support analysis. From this, we found evidence of effectiveness for the following intervention types: universal prevention involving group-based psychological interventions delivered to all participating school students; and indicated prevention involving group-based psychological interventions delivered to students with subthreshold depression. We constructed a Markov model to assess the cost-effectiveness of delivering universal and indicated interventions in the population relative to a 'no intervention' comparator over a 10-year time horizon. A disease model was used to simulate epidemiological transitions between three health states (i.e., healthy, diseased and dead). Intervention effect sizes were based on meta-analyses of randomised control trial data identified in the aforementioned review; while health benefits were measured as Disability-adjusted Life Years (DALYs) averted attributable to reductions in depression incidence. Net costs of delivering interventions were calculated using relevant Australian data. Uncertainty and sensitivity analyses were conducted to test model assumptions. Incremental cost-effectiveness ratios (ICERs) were measured in 2013 Australian dollars per DALY averted; with costs and benefits discounted at 3%. Results: Universal and indicated psychological interventions delivered through face-to-face modalities had ICERs below a threshold of $50 000 per DALY averted. That is, $7350 per DALY averted (95% uncertainty interval (UI): dominates - 23 070) for universal prevention, and $19 550 per DALY averted (95% UI: 3081-56 713) for indicated prevention. Baseline ICERs were generally robust to changes in model assumptions. We conducted a sensitivity analysis which found that internet-delivered prevention interventions were highly cost-effective when assuming intervention effect sizes of 100 and 50% relative to effect sizes observed for face-to-face delivered interventions. These results should, however, be interpreted with caution due to the paucity of data. Conclusions: School-based psychological interventions appear to be cost-effective. However, realising efficiency gains in the population is ultimately dependent on ensuring successful system-level implementation.
Background and purpose: Although the relationship between depression and stroke risk has been investigated, findings in previous reports were conflicting. The aim of this study was to prospectively examine the effect of major depressive episodes (MDE) on stroke incidence and further assess the potential dose-response relationship between number of depression symptoms and subsequent stroke risk in Chinese population. Methods: A total of 199 294 men and 288 083 women aged 30 to 79 years without a history of stroke, heart disease, and cancer in the China Kadoorie Biobank cohort were followed from 2004 to 2013. A World Health Organization Composite International Diagnostic Interview-Short Form was used to access MDE according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Stroke events were ascertained through death certificates, medical records, and health insurance data. Results: Past year MDE was marginally associated with a 15% increased risk of stroke (adjusted hazard ratio, 1.15; 95% confidence interval, 0.99-1.33) in the fully adjusted model, and the association was steeper and statistically significant in individuals aged <50 years, smokers, drinkers, those with higher education degree, body mass index <24.0 kg/m(2), and no history of diabetes mellitus. Moreover, there was a positive dose-response relationship between the number of depression symptoms and increased stroke risk (Ptrend=0.011). In addition, smoking status significantly interacted with MDE on stroke onset (P for multiplicative interaction=0.025). Conclusions: Findings from this large prospective study suggest that the presence of MDE is a risk factor for stroke, especially in smokers.
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Aim: There is growing evidence that depression is associated with an increased mortality risk, but results from studies are ambiguous. To investigate whether depression leads to increased mortality, we reviewed the literature on depression and total mortality in the community. We also performed statistical pooling. Methods: We searched Medline and Psychinfo for relevant articles published between January 1966 and December 2000 and checked the references in the articles found in our search. We used the following inclusion criteria: published in English, Dutch or German language; prospective community based studies describing at least total mortality; the presence of a control group and the use of DSM-criteria or criteria resembling DSM in a reasonable way or by a validated and reliable depression questionnaire in the diagnosis of depression. Results: Twenty-four studies were included in our review. Of the 19 studies reporting data on males and females together, nine reported a significant positive association. The majority of studies showed a positive non-significant association between depression and mortality. No significant negative associations were reported. Overall the summary estimated relative risk was 1.56 (1.31-1.85). Conclusions: Our results support the hypothesis of depression being a risk factor for increased total mortality.
This article describes updates of the meta-analysis command metan and options that have been added since the command's original publication (Bradburn, Deeks, and Altman, metan – an alternative meta-analysis command, Stata Technical Bulletin Reprints, vol. 8, pp. 86–100). These include version 9 graphics with flexible display options, the ability to meta-analyze precalculated effect estimates, and the ability to analyze subgroups by using the by() option. Changes to the output, saved variables, and saved results are also described.
The association between cannabis and depression has received less attention than the links between cannabis use and psychosis (Degenhardt et al., 2003; Degenhardt and Hall, 2006; Di Forti et al., 2007). Over past decades, however, rising rates of cannabis use (Donnelly and Hall, 1994; Hall et al., 1999; Degenhardt et al., 2000; Johns, 2001), depression (Andrews et al., 1998; Cicchetti and Toth, 1998) and suicide (Diekstra et al., 1995; Lynskey et al., 2000) among young adults have increased public concern about the possible role of drug use, including cannabis, in depression and other non-psychotic mental disorders. There has also been increasing advocacy for interventions to prevent and treat problematic cannabis use and depressed mood among young people. This chapter evaluates the nature of the relationship between cannabis use and depression by addressing the following questions: Is there evidence of an association between cannabis use and depression? If there is, what are the potential explanations for the association? What evidence is needed to test these different explanations? What are the public health implications of the evidence to date? Comorbidity between cannabis use and depression Within psychiatry, comorbidity is commonly used to refer to the overlap of two or more psychiatric disorders (Boyd et al., 1984). However, as shall become apparent in the following review, much of the research examining associations between cannabis use and depression has studied relatively infrequent, low-level cannabis use.
• A 16-year prospective study of a general population sample indicates that those who had reported a depression and/or anxiety disorder at baseline experienced 1.5 times the number of deaths expected on the basis of rates for a large reference population. As part of the Stirling County Study (Canada), the information was gathered from 1003 adults through structured interviews and was analyzed by means of a diagnostic computer program. The risk for mortality was assessed using external and internal standards, controlling for the effects of age and sex as well as for the presence of self-reported physical disorders at baseline. Increased risk was found to be significantly associated with affective but not physical disorders and with depression but not generalized anxiety. When this evidence about mortality was combined with information about subsequent psychiatric morbidity among survivors, 82% of those who were depressed at baseline had a poor outcome.
THE past half century has witnessed a marked expansion of mental health facilities in most countries of the world. These trends have been particularly evident in the United States, crystallizing in the current community mental health movement. Both quantitative and qualitative changes are under way in the patterns of mental health facilities. Quantitatively, more clinics and inpatient units have opened and there are increased numbers of psychiatrists and other mental health professionals. Qualitatively, there have been significant shifts in the patterns of mental health care. New types of treatment facilities have been created, ie, day hospitals, family treatment clinics, community mental health centers, and emergency units. These new developments have had, as a major goal, the creation of community alternatives to the large mental hospitals which prior to the turn of the century were the major facilities for the treatment of the mentally ill. For
• Comparison of age-adjusted death rates for inpatient and general populations from three pre-drug era and one post-drug era samples revealed a progressive decline in mortality that was most marked among elderly men. When length of stay was considered, the post-drug era sample showed a 30% reduction in mortality among patients hospitalized less than one year and a 50% reduction among longer-stay patients. The findings fail to support an increased mortality risk associated with the use of psychotropic drugs but dramatize the increased need for psychiatric services resulting from the increased survival of patients, especially those with long-term hospital stays.
• A mortality study was performed on 1190 patients with schizophrenia discharged from hospitals in Stockholm County during 1971. By means of a linkage between the Stockholm County inpatient register and the national causeof-death register, all deaths through 1981 were identified. Compared with the general population, the schizophrenics had an approximately twofold increase in overall mortality. The excess mortality was found in all causes of death but was particularly high in "unnatural death." The suicide mortality was approximately ten times higher among male schizophrenics and 18 times higher among female schizophrenics than in the general population. The methodologic problems with register studies are numerous, but the medical information system used in the study is of great value for psychiatric epidemiologic research.