DSM is Diagnostic and Statistical Manual

DEPRESSION AND ANXIETY 29:425–443 (2012)
Review
THE BEREAVEMENT EXCLUSION AND DSM-5
Sidney Zisook, M.D.,1,2∗ Emmanuelle Corruble, M.D., Ph.D.,3 Naihua Duan, Ph.D.,4,5 Alana Iglewicz, M.D.,1,2
Elie G Karam, M.D.,6,7 Nicole Lanuoette, M.D.,1,2 Barry Lebowitz, Ph.D.,1,8 Ronald Pies, M.D.,9,10
Charles Reynolds, M.D.,11,12 Kathryn Seay, B.S.,13 M. Katherine Shear, M.D.,14
Naomi Simon, M.D.,15 and Ilanit Tal Young, M.D.1,2
Background: Pre-DSM-III (where DSM is Diagnostic and Statistical Manual),
a series of studies demonstrated that major depressive syndromes were common
after bereavement and that these syndromes often were transient, not requiring
treatment. Largely on the basis of these studies, a decision was made to exclude the
diagnosis of a major depressive episode (MDE) if symptoms could be “better accounted for by bereavement than by MDE” unless symptoms were severe and very
impairing. Thus, since the publication of DSM-III in 1980, the official position
of American Psychiatry has been that recent bereavement may be an exclusion
criterion for the diagnosis of an MDE. This review article attempts to answer the
question, “Does the best available research favor continuing the ‘bereavement
exclusion’ (BE) in DSM-5?” We have previously discussed the proposal by the
DSM-5 Mood Disorders Work Group to remove the BE from DSM-5. Methods:
Prior reviews have evaluated the validity of the BE based on studies published
through 2006. The current review adds research studies published since 2006
and critically examines arguments for and against retaining the BE in DSM-5.
Results: The preponderance of data suggests that bereavement-related depression is not different from MDE that presents in any other context; it is equally
genetically influenced, most likely to occur in individuals with past personal and
family histories of MDE, has similar personality characteristics and patterns
1Department of Psychiatry, University of California, San Diego,
California
2Veterans Affairs San Diego Healthcare System and Veterans
Medical and Research Foundation, La Jolla, California
3INSERM U669, Department of Psychiatry, Bicetre University ˆ
Hospital, Assistance Publique–Hopitaux de Paris, France ˆ
4Departments of Biostatistics and Psychiatry, Columbia University, New York, New York
5Division of Biostatistics and Data Coordination at New York
State Psychiatric Institute, New York, New York
6Department of Psychiatry and Clinical Psychology, St. George
Hospital University Medical Center, Balamand University,
Beirut Lebanon
7Faculty of Medicine, Medical Institute for Neuropsychological Disorders (MIND) and Institute for Development, Research,
Advocacy & Applied Care (IDRAAC), Beirut Lebanon
8Departments of Biostatistics and Psychiatry, Columbia University, New York, New York
9Department of Psychiatry, SUNY Upstate Medical University,
Syracuse, New York
10Department of Psychiatry, Tufts University School of
Medicine, Boston, Massachusetts
11Department of Psychiatry, University of Pittsburgh School of
Medicine, Pittsburgh, Pennsylvania
12Department of Community and Behavioral Health Science, University of Pittsburgh Graduate School of Public
Health, Western Psychiatric Institute and Clinic, Pittsburgh,
Pennsylvania
13University of California and San Diego State Joint Doctoral
Program in Clinical Psychology and Veterans Medical, Education and Research Foundation, La Jolla, California
14Complicated Grief Treatment Research Program, Columbia
University School of Social Work and Department of Psychiatry, Columbia University College of Physicians and Surgeons,
New York, New York
15Center for Anxiety and Traumatic Stress Disorders and
Complicated Grief Program, Massachusetts General Hospital,
Boston, Massachusetts
∗Correspondence to: Sidney Zisook, Department of Psychiatry, University of California, 9500 Gilman Dr. #9116A, La Jolla, San Diego,
CA 92093. E-mail: [email protected]
Received for publication 03 October 2011; Revised 24 January
2012; Accepted 28 January 2012
DOI 10.1002/da.21927
Published online in Wiley Online Library (wileyonlinelibrary.com).
C 2012 Wiley Periodicals, Inc.
426 Zisook et al.
of comorbidity, is as likely to be chronic and/or recurrent, and responds to antidepressant medications. Conclusions: We conclude that the BE should not be
retained in DSM-5. Depression and Anxiety 29:425–443, 2012. C 2012 Wiley
Periodicals, Inc.
Key words: bereavement; grief; major depressive disorder; psychiatric diagnosis;
nosology; DSM-5
INTRODUCTION
BACKGROUND
Episodes of major depression often occur in the aftermath of stressful life events, especially those that are associated with loss or humiliation.[1] Thus, it is no surprise
that the death of a loved one, one of the most stressful
life events of ordinary life,[2] is a robust risk factor for
the onset or persistence of a major depressive episode
(MDE).[3] Yet, bereavement is the one life event that
has been singled out by recent editions of the Diagnostic and Statistical Manual (DSM-III, IV, and IV-TR)
to negate the diagnosis of MDE. Thus, since its first
appearance in DSM-III in 1980, the syndromal criteria
for MDE included a criterion admonishing the clinician not to diagnose MDE if the symptoms “are better accounted for by bereavement,” called the “bereavement exclusion” (BE). However, the empirical validity
of this exclusion has not been well established. This
unique stature afforded bereavement, compared to all
other adverse life events, is rational only if major depressive syndromes following bereavement are substantially different than MDEs occurring spontaneously or
following other stressful events. As DSM-5 is now being
planned, it is timely to reexamine the BE, particularly in
the light of new evidence since the last reviews of this
subject.[4, 5] This review assesses studies published after
the previously published reports that address similarities
and differences between bereavement-related depressive
syndromes (BRD) and nonbereavement-related major
depressive episodes (NBRD) to answer the question of
whether the best available research favors continuing the
BE in DSM-5.
The BE is not part of the International Diagnostic
Classification of diseases (ICD). Nor was it part of DSMI or DSM-II. In the 1960s and early 1970s, Paula Clayton and colleagues completed a series of studies[6–10] on
bereaved (mostly) widows and widowers that yielded important data on what to expect in the bereavement period. Her work showed that in the first month of bereavement it is not unusual to experience depressed mood,
sleep disturbance, crying, anorexia/weight loss, and difficulty concentrating/poor memory. By the end of the first
year, most somatic symptoms have improved, although
insomnia, restlessness, and periodic low mood often persist. They reported that a full depressive syndrome was
present in 35–42% of the bereaved at 1 month, decreasing to 16% at 1 year. The 1 year incidence of a full depressive syndrome was 47% in the bereaved versus 8% in
the nonbereaved controls.[11] It was largely on the basis
of this work that the DSM-III added the BE. The goal
of this exclusion was to prevent “medicalizing” a normal
phenomenon, grief, and the subsequent overdiagnosis
of MDE in situations where depressive symptoms were
common, normal, and perhaps even adaptive.[12, 13]
DSM-III AND DSM-III-R
In DSM-III, “uncomplicated bereavement” was both
a V-Code (clinical condition that is not a mental disorder) and an exclusionary criterion for the diagnosis of
MDE. According to DSM-III, “uncomplicated bereavement” “can be used when a focus of attention or treatment is a normal reaction to the death of a loved one
(bereavement). A full depressive syndrome is a normal
reaction to such a loss, with feelings of depression and
such associated symptoms as poor appetite, weight loss,
and insomnia. The reaction to the loss may not be immediate, but rarely occurs after the first 2 or 3 months.
The duration of normal bereavement varies considerably
among different subculture groups.[14]
To help distinguish “uncomplicated bereavement”
from MDE, DSM-III identified several features more
characteristic of one than the other: (1) a bereaved individual typically regards the depressed mood as “normal,”
although the person may seek professional help for relief
of associated symptoms such as insomnia or anorexia; (2)
the diagnosis of MDE is generally not given unless the
symptoms are still present 2–3 months after the loss; and
(3) MDE should be considered in the presence of certain symptoms that are not characteristic of a “normal”
grief reaction, such as guilt about things other than actions taken or not taken by the survivor at the time of
the death, thoughts of death other than the survivor feeling that he or she would be better off dead or should
have died with the deceased person, morbid preoccupation with worthlessness, marked psychomotor retardation,
prolonged and marked functional impairment, and hallucinatory experiences other than thinking that he or she
hears the voice of, or transiently sees the image of, the
deceased person.
DSM-IV AND DSM-IV-TR
In DSM-IV, “uncomplicated bereavement” was replaced by “bereavement.” The time frame for bereavement was more sharply delineated to be 2 months
Depression and Anxiety
The Bereavement Exclusion and DSM-5 427
after the death. Subtle wording changes allowed any
one “severe” feature (i.e. marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation) to be sufficient for a diagnosis of MDE.[15]
Bereavement remained the only life event that excludes
the diagnosis of MDE and MDE is the only psychiatric
disorder superseded by bereavement.
HYPOTHESES
Although the diagnostic conventions described above
were based on the best data available when DSM-III
was first being crafted, newer data generated over the
ensuing 3+ decades allows us to reexamine the validity of maintaining bereavement as an exclusion criterion
for the diagnosis of MDE.[4, 5] Although there has not
been a definitive study to test the validity of the BE,
the preponderance of the available data does not support continuing the BE in DSM-5. Two prior reviews
critically examined the BE,[4, 5] and found that depressive syndromes occurring in the context of bereavement,
BRDs, are similar to NBRDs on almost all MDE validators: demographic features, past personal and family histories of MDE, severity and duration of episodes,
biological features, symptomatic patterns, responses to
antidepressant medications, and long-term outcome.
Subsequently, several newer studies that more directly
address the validity of the BE have been published[16–24]
and are the focus of this review. As in previous reviews,
to answer the question of whether the best available research favors continuing the BE in DSM-5, this review
evaluates the relative validity of two competing hypotheses as follows:
1. BRD is fundamentally different than NBRD; and
2. BRD is not fundamentally different than NBRD.
To the extent that research supports Hypothesis 1, especially if the differences are in the direction of BRD being less severe, chronic, and treatment-responsive, maintaining the BE in DSM-5 is warranted. To the extent the
data support Hypothesis 2, the BE should be dropped
from DSM-5. Wherever possible, this review focuses on
the subset of individuals who, within 2 months after the
loss of a loved one, develop symptoms that technically
meet the broad heterogeneous criteria for MDE (i.e. at
least 5 of 9 symptoms lasting at least 2 weeks); but who—
because of the duration, severity, and impairment features described above—are considered by the DSM-IV
to be experiencing “normal bereavement” rather than
MDE.
METHODS
This review focuses on studies published from January 2007 through
November 2011. Using diagnostic validators as originally proposed by
Robins and Guze[25 ] and expanded by Kendler,[26 ] this review evaluates whether key characteristics that define and characterize MDE
also characterize BRD, and especially those instances of BRD that are
excluded from the diagnosis of MDE based on the DSM-IV BE. If
the predominant weight of the evidence suggests that they do, BRD
may be best conceptualized as a form of MDE rather than an extension of “normal” bereavement. As described previously,[4, 5 ] we
examined three classes of potential validators with subclasses as follows: (1) antecedent validators (e.g. age, gender, familial aggregation
and/or coaggregation, prior history of MDE, and age of onset first
MDE); (2) concurrent validators (e.g. severity and duration of depression, specific symptoms, patterns of comorbidity, emotional, temperamental and personality correlates, functional and cognitive impairment, and associated clinical features); and (3) predictive validators
(e.g. response to treatment and course of illness). The previous reviews included only studies published through 2006; therefore, this
report comprises studies published since then, each of which focuses
more directly on examining the validity of the BE than most previous studies. In addition, this review provides a more explicit discussion of the main arguments for and against the removal of the BE in
DSM-5.
Only English language articles were located with Medline searches
from January 2007 through November 2011. Exploded searches, using “grief or bereavement” and “depression” in the title or abstract
or as key words, were employed. Bibliographies of located articles
were searched for additional studies. Publications were selected for
inclusion if they contained original data; included adults with a recent bereavement who were diagnosed with syndromal depression or
threshold levels for clinically significant depression based on validated
depression interviews or scales; and included one or more nonbereaved
comparison groups. The literature search was conducted by the first
author (SZ) and other authors were invited to add relevant studies that
might have been missed. Although it would have been ideal to conduct a formal meta-analysis of the literature, this was not feasible as
very few primary reports provided confidence intervals (or standard errors) of the estimates or primary data (i.e. contingency or correlations;
Fig. 1).
Each validator was scored in terms of whether it provided more support for Hypothesis 1 (BRD does not resemble NBRD and continuing
the BE in DSM-5 is warranted) or for Hypothesis 2 (BRD resembles
NBRD and continuing the BE in DSM-5 is not warranted). The initial
judgment was made by the first author (SZ) subject to discussion and a
consensus decision if any of the coauthors disagreed. If BRD was statistically and clinically similar to NBRD, it was scored as H.2. (favoring
Hypothesis 2) for the corresponding validator. If the BRD was unlike
NBRD on a given validator, it was generally scored as H.1. (favoring
Hypothesis 1). However, in those instances when BRD was different
than NBMR but the difference was in the direction of being consistent
with well-known characteristics of MDE, such as having more previous episodes of depression than the NBRD control group, the validator
was scored as H.1./H.2. (not favoring either Hypothesis). H.1./H.2.
was also used for results that were equivocal or not clearly favoring
either hypothesis, such as when “uncomplicated” BRD resembled “uncomplicated” NBRD, but neither resembled “complicated” depressive
syndromes[16 ].
To conserve space, studies that were previously reported in
comprehensive reviews of the BE[4, 5 ] are not included in this
report.
RESULTS
Nine informative studies from four countries published since the last comprehensive reviews on the validity of the BE are reviewed: five large populationbased studies[16–18,23, 24] and four studies of clinical
Depression and Anxiety
428 Zisook et al.
Figure 1. Selection of studies for review.
populations[19–22]. The text below briefly summarizes
results from each of the nine studies. Table 1 provides
a detailed summary of each key study and Tables 2–4
tabulate results related to each validator. The last three
columns in Tables 2–4 provide summary judgments of
whether the data best supports Hypothesis 1 (noted as
H.1), Hypothesis 2 (noted as H.2.), or is too close to call
(H.1./H.2.).
In the first of these studies, Wakefield et al.[16] provided a secondary analysis from the National Comorbidity Survey of 8,089 persons representative of the United
States population and identified 157 individuals whose
major depressive syndromes were triggered by bereavement (BRD) and 710 triggered by other losses (NBRD).
They further divided the sample into uncomplicated
and complicated cases based on an approximation of
the DSM-IIIR duration, severity, and impairment criteria for the BE. Wakefield et al. defined a “complicated
case” as a depressive syndrome that satisfies at least two
of the following features: morbid feelings of worthlessness, psychomotor retardation, suicidal ideation, suicide
attempts, marked functional impairment, and duration
>12 weeks. The use of this terminology is unfortunate
as it invites confusion with the term “complicated grief,”
which is a bereavement-related syndrome distinct from
MDE.[27] However, using this terminology, Wakefield
et al. identified four groups as follows: (1) uncomplicated BRD (n = 56), (2) complicated BRD (n = 101),
(3) uncomplicated NBRD (n = 174), and (4) complicated NBRD (n = 536). The main findings were that
uncomplicated BRD resembled uncomplicated NBRD
on almost all features measured (e.g. age, gender, race,
Depression and Anxiety
The Bereavement Exclusion and DSM-5 429
TABLE 1. Overview of studies published 2007–2011
Type of Comparison Type of Depression Life events Time since
Author study Sample group comparison assessment assessment death
Wakefield
et al.[16 ]
Community-based
epidemiologic study from
the NCS involving 8,098
persons ages 15–54
157 (1.9%) with BRD
56/157 “uncomplicated”
BRD (<12 weeks and not
impaired AND
<2 of the
following symptoms:
worthlessness,
psychomotor retardation,
suicidal ideation, or suicide
attempt)
101/157 “complicated” BRD
(>12 weeks or impaired
OR
≥2 of the following
symptoms: worthlessness,
psychomotor retardation,
suicidal ideation or suicidal
attempt)
710 (8.8%) with NBRD
triggered by other loss
174/710 “uncomplicated”
other loss-related depression
(>12 weeks and not
impaired AND
<2 of the
following symptoms:
worthlessness,
psychomotor retardation,
suicidal ideation, or suicide
attempt)
536/710 “complicated” other
loss-related depression (>12
weeks OR impaired OR
≥2 of the following
symptoms: worthlessness,
psychomotor retardation,
suicidal ideation, or
suicidal attempt)
BRD versus NBRD Structured
interview—
DSM-III-R
criteria for
MDD
Structured interview
<3 months
and
>3
months
Kendler
et al.[17 ]
Community-based
epidemiologic study of
twins from the VATS
PSUD involving 266,409
person–months of data
from 9,242 individuals
83 (1%) with BRD
23/82 (28%) with BRD were
excluded by DSM BE
criteria (duration
<2
months, no psychomotor
retardation, suicidal
ideation, or severe
functional impairment.
(uncomplicated BRD group)
167 (1.8%) with NBRD
related to other stressful
life events
55/167 (25%) also had
episodes lasting
<2
months. and no
psychomotor retardation,
suicidal ideation, or severe
mood impairment.
(uncomplicated NBRD
group)
BRD versus NBRD SCID At each interview (four
times over 10 years)
participants provided
information on life
events in each of the 12
preceding months
<2 months
and 2–12
months
Kessing
et al.[20 ]
Clinical sample: 301 first
episode MDE (ICD-10)
inpatients or outpatients in
East Denmark
26 (8.6%) with BRD 275 (91.4%) with NBRD
163/275 (54.2%) experienced
other stressful life events
within 6 months prior to
the onset MDE
112/275 (37.2%)—no
bereavement or other
stressful life event within 6
months onset of NBRD
BRD versus NBRD SCAN IRLE
<6 months
Depression and Anxiety
430 Zisook et al. TABLE 1. Continued Type of Comparison Type of Depression Life events Time since Author study Sample group comparison assessment assessment death Corruble et al.[19 ] Case-control, cross sectional study of 17,988 self-referred patients seeking treatment for depression (DSM-IV MDE symptoms criteria) 1,521 (8.5%) patients assessed as “bereaved” rather than MDE based on clinician’s assessment of DSM-IV criteria and BE made up the BE group 1,521 patients from the remaining 16,467 patients matched for age, gender, educational level, and number of previous MDEs made up the MDE control group
—292/1,521 (19.2%) also
recently bereaved
—1,229/1,521 (80.8%) not
recently bereaved
BRD versus NBRD MINI LEI for events
occurring in the 3
months preceding
the current
depressive episode
<2 months for
the BE group
<3 months for
the MDE
control group
with recent
bereavement
Corruble
et al.[21, 22 ]
Case-control study of 12,615
patients seeking treatment
for depression assessed
before and 6 weeks after
antidepressant treatment
1,138 (9%) patients assessed
as “bereaved” rather than
MDE based on clinician’s
assessment of DSM-IV
criteria and BE made up
the BE group
1,138 from the remaining
11,477 patients matched
for age, gender,
educational level, and
number of previous MDEs
made up the MDE control
group
BRD versus NBRD Clinical
diagnosis
MDE
N/A
< 2 months for
BE group
Karam
et al.[18 ]
Prospective community
household survey of 658
adults in Lebanon in two
phases: 1989 and 1991
—193 subjects with
depression at phase 1 (365
episodes)
95/365 (26%) episodes
related to bereavement
(BRD)
12/95 (12.6%) excluded from
diagnosis of MDE (BRD
+duration 2–8 weeks
+ no
psychomotor retardation,
worthlessness, or suicidal
ideation or attempts)
270/365 (74%) episodes not
related to bereavement
(NBRD)
35/270 (13%) with duration
2–8 weeks
+ no
psychomotor retardation,
worthlessness or suicidal
ideation or attempts
BRD versus NBRD DIS Structured interview 2 months and
life-time
Depression and Anxiety
The Bereavement Exclusion and DSM-5 431
TABLE 1. Continued
Type of Comparison Type of Depression Life events Time since
Author study Sample group comparison assessment assessment death
Mojtabai[23 ] Longitudinal
community-based
epidemiological study
from the NESARC
involving 43,093 adults
446/43,093 (1.1%) lifetime,
single, brief BRD
162/446 (36.3%) BRD
without marked
impairment or
psychomotor slowing or
feelings of worthlessness or
suicidal ideation (DSM-IV
BRD)
753/43,093 (1.7%) lifetime,
single, brief NBRD
No lifetime MDE
Nonbrief (
>2 months single
episode
Multiple depressive episodes
Lifetime, single, brief
BRD versus lifetime,
single, brief NBRD
versus no lifetime MDE
versus nonbrief (
>2
months single episode
versus multiple
depressive episodes
AND DSM-IV BRD
versus all other single
episode MDE
AUDADIS AUDADIS
<2 months for
the DSM-IV
BRD group
and all other
“brief”
depressive
episodes
Gilman
et al.[24 ]
Longitudinal
community-based
epidemiological study
from the NESARC
involving 43,093 adults
8,626/43,093 (20%) with
lifetime prevalence of
MDE or
bereavement-excluded
depression
196/8,626 (2.3%)
Bereavement-excluded
BRD—excluded from
diagnosis of MDE by DSM
BE criteria (BRD and
duration
<2 months, no
psychomotor retardation,
suicidal ideation, or severe
functional impairment)
566/8,626 (6.2%)
“Complicated” BRD
(episodes lasting
>2
months and/or marked
functional impairment,
feelings of worthlessness,
psychomotor retardation,
suicidal ideation, or
psychotic features
7,864/8,626 (91.5%) with
NBRD
Excluded BRD versus
nonexcluded BRD
(“complicated
bereavement”) versus
NBRD
AUDADIS AUDADIS
<2 months for
the BE group
BRD, bereavement-related depression; NBRD, nonbereavement-related depression; MDE, major depressive episode; NCS, National Comorbidity Survey; VATS PSUD, Virginia Twin study
of Psychiatric and Substance Use Disorders; SCID, structured clinical interview for DSM-III-R axis I disorders; SCAN, schedule for clinical assessment in neuropsychiatry; IRLE, interview of
recent life events; MINI, mini-international neuropsychiatric inventory; LEI, life events inventory; DIS, diagnostic interview schedule; NESARC, National Epidemiologic Survey on Alcohol
and Related Conditions; AUDADIS, alcohol use disorder and associated disabilities interview schedule-IV.
Depression and Anxiety
432 Zisook et al. TABLE 2. MDE validators: antecedent Author Age Gender Family history MDE Past history MDE Age of onset 1st MDE Wakefield et al.[16 ] “B triggered” depression = “other loss triggered”‘ depression H.2.** Uncomplicated “B triggered” depression = uncomplicated “other loss triggered” depression H.2.** “B triggered” depression = “other loss triggered” depression H.2.** Uncomplicated “B triggered” depression = uncomplicated “other loss triggered” depression H.2.** “B triggered” depression = “other loss triggered” depression on mean number recurrent episodes MDE H.2.** Uncomplicated B and other loss triggered depression < complicated depressions on mean number recurrent episodes MDE H.1./H.2.** Kendler BRD = NBRD BRD = NBRD BRD = NBRD BRD = NBRD BRD = NBRD et al.[17 ] H.2.** H.2.** H.2.** H.2.** H.2.** ‘Uncomplicated NBRD = ‘uncomplicated’ NBRD H.2.** More men met criteria for “uncomplicated BRD” than for uncomplicated NBRD H.1.** BRD = NBRD in percentage of co-twins with MDE H.2.** BRD = NBRD in number of previous of MDE H.2.** Kessing et al.[20 ] BRD = other life event-related NBRD (but older than no life event-related NBRD) H.2.** BRD = other life event-related NBRD = no life event-related NBRD H.2.** BRD = other life event-related NBRD = no life event-related NBRD H.2.** Corruble et al.[21, 22 ] BE older than the entire MDE group (before matching) H.1.** BE had more previous episodes than the entire MDE group (before matching) H.1./H.2.**
Karam
et al.[18 ]
BRD = NBRD
H.2.**
BRD without conditional
symptoms = NBRD
without conditional
symptoms
H.2.**
Mojtabai[23 ] Single, brief BRD = single, brief
NBRD
H.2.**
DSM-IV BRD > all other BRD +
NBRD to be age 50+ years
H.1.**
Single, brief BRD = single, brief
NBRD
H.2.**
Single, brief BRD = single, brief
NBRD
H.2.**
Single, brief BRD >
single, brief NBRD on
age of onset of episode
after age 50 years
H.1.**
Gilman
et al.[24 ]
B excluded BRD = “complicated
BRD”
H.2.**
B excluded BRD = “complicated BRD”
H.2.**
B excluded BRD < NBRD B excluded BRD < NBRD
H.1.** H.1.**
B, bereavement; BRD, bereavement-related depression; NBRD, nonbereavement-related depression; MDE, major depressive episode.
**H.1. = favors Hypothesis 1; **H.2. = favors Hypothesis 2; H.1./H.2. = equivocal.
Depression and Anxiety
The Bereavement Exclusion and DSM-5 433
TABLE 3. MDE validators: concurrent
Author
Severity of
depression Duration
Prevalence of
“conditional”
symptoms
(psychomotor
retardation,
worthlessness,
suicidal
ideation/attempt) Comorbidity
Temperament and
personality
Functional
impairment and
cognitive function Receiving treatment
Other clinical
features
Wakefield
et al.[16 ]
Uncomplicated B
triggered
depression
=
uncomplicated
other loss
triggered
depression
H.2.**
Uncomplicated B
and other loss
triggered
depression
<
complicated
depressions
H.1./H.2.**
Uncomplicated B
triggered
depression
=
uncomplicated
other loss
triggered
depression on
duration longest
episode
H.2.**
Uncomplicated B
and other loss
triggered
depression
<
complicated
depressions on
duration longest
episode
H.1./H.2.**
Uncomplicated B
triggered depression
= uncomplicated
other loss triggered
depression on
suicide attempts
H.2.**
Uncomplicated B
and other loss
triggered depression
< complicated
depressions on
suicide attempts
H.1./H.2.**
Uncomplicated B
triggered depression
= uncomplicated
other loss triggered
depression
H.2.**
Uncomplicated B
and other loss
triggered depression
< complicated
depressions
H.1./H.2.**
Uncomplicated B
triggered depression
= uncomplicated
other loss triggered
depression any
treatment,
antidepressant
medications and
hospitalization for
depression
H.2.**
Uncomplicated B
and other loss
triggered depression
< complicated
depressions on
treatment or
antidepressant
medications
H.1./H.2.**
Uncomplicated B
triggered depression
= uncomplicated
other loss triggered
depression on
melancholic feature
and 8/9 depressive
symptoms
H.2.**
Uncomplicated B
and other loss
triggered depression
< complicated
depressions on
melancholic features
H.1./H.2.**
Kendler
et al.[17 ]
BRD
= NBRD on
mean duration of
episode
H.2.
No significant
interaction
between
depression group
(BRD versus
NBRD) and
“uncomplicated”
features
H.2.**
BRD
= NBRD on
comorbidity with
any anxiety disorder
and/or substance use
disorder
H.2.**
No significant
interaction between
depression group
(BRD versus
NBRD) and
“uncomplicated”
features
H.2.**
BRD
= NMRD on
personality traits of
extraversion
H.2.**
BRD lower rates of
neuroticism than
NBRD
H.1.**
No significant
interaction between
depression group
(BRD versus
NBRD) and
“uncomplicated”
features
H.2.**
Fewer BRD patients
sought treatment
(27% versus 36%)
H.1.**
BRD
= NBRD on
number of
symptoms endorsed
H.2.**
No significant
interaction between
depression group
(BRD versus
NBRD) and
“uncomplicated”
features
H.2.**
Depression and Anxiety
434 Zisook et al. TABLE 3. Continued Author Severity of depression Duration Prevalence of “conditional” symptoms (psychomotor retardation, worthlessness, suicidal ideation/attempt) Comorbidity Temperament and personality Functional impairment and cognitive function Receiving treatment Other clinical features Kessing et al.[20 ] BRD = other life event-related NBRD = no life event-related NBRD H.2.** BRD = other life event-related NBRD = no life event-related NBRD H.2.** BRD = other life event-related NBRD = no life event-related NBRD on suicidal ideation H.2.** BRD = other life event-related NBRD = no life event-related NBRD on psychiatric comorbidity including anxiety symptoms and alcohol/drug abuse H.2.** BRD = other life event-related NBRD = no life event-related NBRD on neuroticism and personality disorders H.2.** BRD = other life event-related NBRD = no life event-related NBRD on inpatient or outpatient treatment H.2.** BRD = other life event-related NBRD = no life event-related NBRD on melancholic and psychotic features H.2.** Corruble et al.[19 ] BE group = matched MDE controls with B on severity of
symptoms
H.2.**
BE group had
more severe
symptoms and
more symptoms
than MDE
controls without
B
H.1./H.2**
BE group =
matched MDE
controls with B on
suicidal ideation,
psychomotor
retardation, and
worthlessness
H.2**
BE group had more
suicidal ideation and
worthlessness than
MDE controls
without B
H.1./H.2**
BE group had more
sadness, reduced
sleep and appetite,
numbness and
pessimism than
matched MDE
group with and
without B
H.1./H.2**
Corruble
et al.[21, 22 ]
BE group =
matched MDE
controls on
baseline severity
of depression
H.2
BE group =
matched MDE
controls on
psychomotor
retardation and
worthlessness but
had more suicidal
ideation at baseline
H.2
BE group = MDE
control group on
both immediate and
delayed recall at
baseline and at
follow-up after
treatment
H.2.**
Depression and Anxiety
The Bereavement Exclusion and DSM-5 435
TABLE 3. Continued
Author
Severity of
depression Duration
Prevalence of
“conditional”
symptoms
(psychomotor
retardation,
worthlessness,
suicidal
ideation/attempt) Comorbidity
Temperament and
personality
Functional
impairment and
cognitive function Receiving treatment
Other clinical
features
Karam
et al.[18 ]
BRD
> NBRD on
duration
> 8 weeks
(71% versus 55%)
H.1./H.2.**
B excluded group
= NBRD group of
similar duration
and severity on
duration
H.2.**
Mean duration of
depressive episode
in BRD 29.2 weeks
compared to 28.8
weeks in NBRD
H.2.**
BRD
= NBRD on
prevalence of
“conditional”
symptoms
(psychomotor
retardation,
worthlessness and
suicidal
ideation/attempts)
H.2.**
BRD
= NBRD on
marked dysfunction
H.2.**
B excluded group
=
NBRD group of
similar duration and
severity on marked
dysfunction
H.2.**
BRD
= NBRD on
treatment
H.2.**
B excluded group
=
NBRD group of
similar duration and
severity on
treatment
H.2.**
BRD
= NBRD on
prevalence of
sadness, disturbed
sleep, problems
concentration,
changes in weight
and fatigue
H.2.**
Mojtabai[23 ] Single, brief BRD
<
single, brief NBRD
to have
worthlessness and
suicidal ideation
H.1.**
DSM-IV BRD
< all
other BRD
+
NBRD to have
worthlessness and
suicidal
H.1.**
Single, brief BRD
=
single, brief NBRD
on dysthymia and
alcohol abuse but
single, brief BRD
<
single, brief NBRD
on anxiety disorder
comorbidity
H.1./H.2.**
Single, brief BRD
<
single, brief NBRD
on role functioning
H.1.**
Single, brief BRD
<
single, brief NBRD
to receive treatment
H.1.**
DSM-IV BRD
< all
other BRD
+
NBRD to receive
treatment
H.1.**
Single, brief BRD
<
single, brief NBRD
to have increased
sleep or fatigue but
more likely to have
decreased sleep
H.1./H.2.**
DSM-IV BRD
< all
other BRD
+
NBRD to have
increased sleep and
more likely to have
decreased sleep
H.1./H.2.**
Depression and Anxiety
436 Zisook et al. TABLE 3. Continued Author Severity of depression Duration Prevalence of “conditional” symptoms (psychomotor retardation, worthlessness, suicidal ideation/attempt) Comorbidity Temperament and personality Functional impairment and cognitive function Receiving treatment Other clinical features Gilman et al.[24 ] Bereavement- excluded BRD = “Complicated BRD” on previous history of panic disorder, generalized anxiety
disorder, social
phobia, and alcohol
dependence but
both bereavementexcluded BRD and
“complicated BRD”
< NBRD on social
phobia
H.1./H.2.**
Bereavementexcluded BRD =
“complicated BRD”
on all personality
disorders but both
bereavementexcluded BRD and
“Complicated
BRD” < NBRD on
avoidant, obsessive
compulsive,
paranoid, and
schizoid
personalities
H.1./H.2.**
Bereavementexcluded BRD =
“complicated BRD”
on psychosocial
impairment but
both bereavementexcluded BRD and
“complicated BRD”
< NBRD on
psychosocial
impairment
H.1./H.2.**
Bereavementexcluded BRD =
“complicated BRD”
treatment received
but both
bereavementexcluded BRD and
“complicated BRD”
< NBRD on
treatment received
H.1./H.2.**
B, bereavement; BRD, bereavement-related depression; NBRD, nonbereavement-related depression; MDE, major depressive episode.
**H.1. = favors Hypothesis 1; **H.2. = favors Hypothesis 2; H.1./H.2. = equivocal.
Depression and Anxiety
The Bereavement Exclusion and DSM-5 437
TABLE 4. MDE validators: predictive
Author Outcome Future episodes
Kendler et al.[17 ] BRD = NBRD in percent with subsequent episodes
H.2.**
Kessing et al.[20 ] BRD = NBRD on remission with first time
treatment
H.2.**
Corruble et al.[19 ] BE group = MDE control group on risk of
recurrence
H.2.**
Corruble et al.[21, 22 ] BE group = MDE control group in percentage
responding to treatment (38% versus 40%) and no
longer meeting DSM-IV symptom criteria for
MDE (80% versus 82%) at 6 weeks
H.2.**
Karam et al.[18 ] BRD = NBRD in risk of recurrence
H.2.**
Risk of recurrence for BRD the same in those whose
1st depressions were BRD (18.8%) as those whose
1st depressions were not related to bereavement
(19.1%); risk of recurrence for NBRD the same in
those whose 1st depressions were BRD (43.8%) as
those whose 1st depression was not related to
bereavement (47.3%)
H.2.**
B excluded group = NBRD group of similar duration
and severity (duration 2–8 weeks + no
psychomotor retardation, worthlessness, or
suicidal ideation or attempts) on risk of recurrence
H.2.**
Mojtabai[23 ] Single, brief BRD < single, brief NBRD on risk of
recurrence
H.1.**
DSM-IV BRD < all other BRD + NBRD on risk of
recurrence
H.1.**
DSM-IV BRD = no history of MDD group on risk
of recurrence
H.1.**
Gilman et al.[24 ] Bereavement-excluded BRD = “Complicated BRD”
for risk of recurrence over 3-year follow-up but
both bereavement-excluded BRD and
“complicated BRD” < NBRD on risk of
recurrence
H.1./H.2.
B, bereavement; BRD, bereavement-related depression; NBRD, nonbereavement-related depression; MDE, major depressive episode.
**H.1. = favors Hypothesis 1; **H.2. = favors Hypothesis 2; H.1./H.2. = equivocal.
8/9 depressive symptoms, severity, melancholic features,
suicide attempts, treatment, and medications); and that
uncomplicated cases (whether BRD or NBRD) were different than complicated cases on severity, melancholic
features, suicide attempts, interference with life, treatment, and medications. The results of this study could
lead to either of two conclusions as follows: (1) since uncomplicated BRD resembles uncomplicated NBRD, the
BE should be eliminated (i.e. there is nothing distinctive about depressive syndromes following bereavement
compared to depressive syndromes following other, nonbereavement adverse life events) or (2) since uncomplicated cases of both BRD and NBRD are less severe than
complicated cases, all uncomplicated cases should be excluded from the diagnosis of MDE (i.e. the BE should
be extended to all uncomplicated case of depressive syndromes related to loss. The investigators of this study
favored the latter conclusion: “The DSM Major Depressive Disorder (MDD) BE likely should be reconsidered
in DSM-5, with equal attention to bereavement and nonbereavement triggers of intense sadness.” (p. 439).[16]
In contrast, a similar secondary analysis of a large
population-based study, finding comparable results,
came to the opposite conclusion. To determine the
Depression and Anxiety
438 Zisook et al.
similarities and differences of BRD and NBRD related
to other stressful life events, Kendler et al.[17] identified
and compared individuals on a range of MDD validators
from the Virginia Twin Registry. They also evaluated
whether cases of BRD that also met DSM-IIIR criteria for “normal grief” were qualitatively distinct from
other depressive cases. Kendler et al. identified 82 cases
of BRD and 224 with NBRD related to other stressful
life events. The two groups did not differ in age at onset
of MDD, number of prior episodes, duration of index
episode, number of endorsed “A criteria,” risk for future
episodes, pattern of comorbidity, levels of extraversion,
risk for MDD in their co-twin, or the proportion meeting criteria for “normal grief.” However, individuals with
BRD were slightly older, more likely to be female, had
lower levels of neuroticism, treatment seeking and guilt,
and higher levels of fatigue and loss of interest. Interaction analyses failed to find unique features of people
meeting criteria for both BRD and normal grief compared to those whose depression was related to other life
stressors. Given the marked similarities between BRD
and NBRD, and the failure to find differences between
cases of BRD and NBRD meeting or not meeting “normal grief criteria,” the investigators concluded that the
results argue against the continued use of the “BE rule”
in DSM-5. An exchange of Letters to the Editor between
Wakefield et al.[28] and Kendler et al.[29] did not resolve
the different interpretations of similar results between
the two groups of investigators.
The third study[18] is an update with new analyses relevant to the BE from a previously published study.[30]
Comparing BRD to NBRD in a large, population-based,
prospective study in Lebanon, Karam et al.[18] reported
that the prevalence of the DSM-IV “conditional criteria”
(psychomotor retardation, worthlessness, suicidal ideas
or attempts, and less than 8 weeks duration) was substantial in the total sample (N = 685) and did not differ
between bereaved and nonbereaved groups with the exception of more individuals with BRD having a duration
of depressive symptoms>8 weeks. In addition, the global
symptom profile of depressive symptoms and their risk
for recurrence was similar in bereaved and nonbereaved
subjects. Compared to the bereaved subgroup who did
not meet any of the “conditional” symptom criteria (N =
34), the nonbereaved group who also did not endorse
any of the conditional symptoms (N = 78), had similar
duration of depressive episodes, treatment, and marked
dysfunction. Finally, the group who would have been
excluded from the diagnosis of MDE based on duration
and conditional symptoms were no different than the
group of nonbereaved persons with a similar duration
and symptom profile on age of onset or risk or recurrence. The investigators conclude that BRDs similarity
to NBRD in symptom profile, course, dysfunction, and
treatment does not support the validity of the DSM-IV
BE.
Fourth, in a French national case-control, crosssectional study of self-referred individuals seeking treatment for depressive symptoms, 17,988 adults met DSMIV symptom criteria for MDE.[19] However, 1,521 were
considered “not depressed” by their evaluating physicians on the basis of the BE (the “BE excluded group”).
The control group was 1,521 demographically matched
patients who were diagnosed with MDE (the “MDE
group”), of whom 292 had a recent (within 3 months)
bereavement. Interestingly, the BE excluded group did
not differ from the 292 recently bereaved patients who
were diagnosed with MDE on the total number of
symptoms, severity of depression, or on any of the
three symptoms identified by the DSM as designating
MDE—worthlessness, psychomotor retardation, or suicidal ideation. These results directly question the reliability of the DSM-IV BE criteria. In addition, the BE
excluded group had more MDE symptoms, including
worthlessness and suicidal thoughts, and greater severity of depression than the MDE control group. This
study suggests that the BE criteria often are misapplied and may inadvertently lead to some severely depressed patients failing to be diagnosed; thus, bereaved
and seriously depressed patients may be at risk for prolonged and unnecessary suffering and not receiving appropriate treatment. In a Letter to the Editor discussing
this study, Clayton states that it is not surprising that
a bereaved person with MDE may have more symptoms than a depressed person without a significant stress
such as bereavement. She concludes that “if the criteria are confusing and relegate people seeking treatment
after bereavement to a V code, it may be that the instructions are poorly written and that Criteria E for
MDE should be deleted, but the V code should remain”
(p. 359).[31] Shear et al. also recommended retaining the
V code and provided suggestions for how it could be
maximally useful.[27]
The fifth and sixth studies comprises two reports
from an additional French national case-control study
of 11,510 adult outpatients seeking treatment for
depression.[21, 22] One thousand one hundred thirtyeight (9.9%) individuals met criteria for DSM-IV MDE
BE criteria (BE group). This BE group was matched
for age, gender, educational level, and number of previous depressive episodes with 1.138 MDE patients (MDE
group). In one report,[22] the groups were compared
for the delayed paragraph recall index from the Wechsler Memory Scale—revised at baseline and at 6-week
follow-up. The groups did not differ in terms of immediate or delayed recall at baseline or follow-up. In
a second report,[21] the groups were prospectively accessed for outcome after 6 weeks of antidepressant treatment. The BE group had higher levels of baseline MDE
symptoms and self-rated severity than MDE controls,
but were equally likely to respond to treatment. Corruble et al. concluded that bereavement, just as any other
stressful event, can be noted, but should not influence
diagnostic or treatment decisions.
In the seventh study, Kessing et al.[20] explored the
Danish Psychiatric Central Research Register of discharged inpatient or outpatients to compare characteristics associated with first onset MDE following
Depression and Anxiety
The Bereavement Exclusion and DSM-5 439
bereavement (N = 26) to MDE following other stressful
life events (N = 163), as well as to MDE occurring in
the absence of life adversity (N = 112). They reported
that patients who had experienced bereavement did not
differ from patients with other stressful life events or
from patients without stressful life events with respect
to: sociodemographic variables; family history; severity of depression; specific symptoms or the prevalence
of melancholic, atypical, or psychotic features; psychiatric comorbidity; or response to antidepressant treatment. Their conclusion was that first-episode MDD following bereavement is not substantially different from
other kinds of first-episode depression. This study did
not separately analyze specific DSM “conditional” criteria used for the BE and did not focus specifically
on the 2-month period following loss of a loved one;
rather, the study extended this period up to 6 months.
However, the results were strikingly consistent with the
others reviewed above, indicating that BRD resembles
NBRD on most antecedent, concurrent, and predictive
validators.
The eighth and ninth studies comprise from the two
reports from 43,093 participants of the National Epidemiologic Survey on Alcohol and Related Conditions
(NESARC). In the first of these, Mojtabai[23] compared
sociodemographic features, clinical characteristics, and
risk of new depressive episodes in a 3-year follow-up
of individuals with a lifetime, single, brief (<2 months)
BRD (N = 446) with those with a lifetime, single, brief
NBRD (N = 753). Compared to participants with single,
brief NBRD, those with single, brief BRD were somewhat older and more likely to be black. There was no
difference in family history of MDE, lifetime dysthymia,
or alcohol dependence. They were equally likely to report impairment in work functioning, but less likely to
recall impairment in social functioning, comorbid anxiety disorders, or treatment history for the index episode.
Participants with lifetime, single, brief BRD were less
likely than those with lifetime, single, brief NMRD to
experience fatigue, increased sleep, feelings of worthlessness, and suicidal ideation, but more likely to report
decreased sleep. The risk of new depressive episodes during the 3-year follow-up among participants with single,
brief BRD was significantly lower than among participants with single, brief NBRD (8.2% versus 14.7%); but
similar to participants with no lifetime history of MDE
(8.2% versus 7.5%). In a further analysis of a subset of
162 of the single, brief BRD group who also did not have
marked impairment or any of the DSM-IV conditional
symptoms of psychomotor slowing, feelings of worthlessness or suicidal ideation (called the DSM-IV BRD
group) compared to all other 1,037 individuals with single, brief MDE (including those with NBRD and those
with BRD who had marked impairment and/or one of
the conditional symptoms), the former group was found
to be older, less likely to receive treatment, and less likely
to experience increased sleep, but more likely to experience decreased sleep and new depressive episodes in
follow-up. No comparisons were reported between the
DSM-IV BRD group and the NBRD group with similar conditions (i.e. no marked impairment, psychomotor
slowing, feelings of worthlessness, or suicidal ideation).
Mojtabai’s conclusions stand in contrast to those of previous reviews of Zisook et al.[4, 5] or of most of the studies
reviewed above.[17–21,32] He concludes that because single, brief BRD has distinct sociodemographic and symptomatic profiles, and the risk of new episodes of MDE in
individuals with BRD is more like the risk in the nondepressed members of the general population than in other
depressed populations, his data support preserving the
DSM-IV BE for MDE in the DSM-5.
Finally, Gilman et al.[24] also used data from two
waves of the NESARC (n = 43,093) to compare lifetime
bereavement-excluded depression (N = 196) and “complicated bereavement” (N = 566) to MDE (N = 7,864)
with respect to antecedent validators (e.g. past and family history), concurrent validators (e.g. depression severity and treatment), and predictive validators (recurrence
during 3 years follow-up). Again, inviting confusion with
complicated grief,[27] this group defined complicated bereavement as depression beginning just after someone
close died but persisting for more than 2 months or
exhibiting marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychomotor retardation, or psychotic symptoms. There
were no differences between groups in family history of depression or alcoholism; past panic disorder,
generalized anxiety disorder, or alcoholism. However,
compared to individuals with MDE, individuals with
bereavement-excluded depression had fewer lifetime depressive episodes, lower risks of past social phobia and
certain personality disorders, less psychosocial impairment (P < .001), a lower odds of seeking treatment, and a
lower risk of psychiatric disorders during a 3-year followup period. This same pattern of differences was observed
between individuals with “complicated bereavement”
and MDE. The investigators caution against interpreting the differences between bereavement-excluded depression and MDE as supporting the validity of the BE,
as: (1) there also were several similarities, (2) many of
the individuals with bereavement-excluded depressions
still had a clinically significant depressive episode, and (3)
bereavement-excluded depression was rated similarly to
“complicated bereavement” on all antecedent, concurrent, and predictive validators. They also noted that the
prevalence of bereavement-excluded depression was low,
0.5% of the overall population and only 2.3% of individuals meeting criteria for depression, and therefore did
not support the concern that has been raised regarding
a “massive pathologization” of normal sadness—should
the BE be removed in DSM-5.
DISCUSSION
Grief hurts. The permanent loss of a loved one can be
gut wrenching and feelings of sadness and yearning may
rival the most intense experiences of emotional pain the
individual has ever experienced. Although the dysphoria
Depression and Anxiety
440 Zisook et al.
associated with grief may resemble that of MDE, grief
has a different character: more likely decreasing in intensity over days to weeks; occurring in waves, or so called
“pangs” of grief associated with thoughts or reminders
of the deceased rather than the more persistent, pervasive sadness of MDE; often accompanied by positive
emotions and humor so uncharacteristic of MDE; and
featuring preoccupation with thoughts and memories of
the deceased rather than the self-critical or pessimistic
ruminations seen in MDE.[33, 34] Few would argue that
the sadness and longing of ordinary grief should be labeled or medicalized, diagnosed, or treated. The vast
majority of bereaved individuals—who hurt, grieve, feel
sad—do not require professional help even if they have
some trouble sleeping, eating, or concentrating. Indeed,
most bereaved individuals, despite their acute anguish
and distress, do not meet DSM-IV criteria for MDE
and regain their emotional footing without professional
attention.
But when a full depressive syndrome is present, meaning symptoms are present most of the day, nearly every
day for at least 2 weeks, during the period 2–12 weeks
following bereavement, and associated with significant
distress or impairment, should that depression be diagnosed and potentially treated? The focus of this paper is
on whether the data supports the ICD’s answer (depression is diagnosed regardless of the precipitating stressor) or the DSM’s (depression is diagnosed only when
psychomotor retardation, morbid preoccupation with
worthlessness, psychotic symptoms, suicidal ideation, or
marked functional impairment are present). Although
none of the studies to date provide a definitive answer,
the preponderance of data previously reviewed[4, 5] as
well as data from the newer studies reported here support
the ICD.
The validity of the BE has received attention in the lay press, and has been debated by
grief and bereavement experts, and by the APA’s
DSM-5 Mood Disorders Taskforce, with the latter
proposing elimination of the bereavement exclusion
from DSM-5, (http://www.dsm5.org/proposedrevision/
Pages/DepressiveDisorders.aspx.). But the issue is not
simple and intelligent, compassionate, competent clinicians and investigators have argued for each side of the
debate.[13] Below, we list several of the arguments against
removing the BE and our responses:
1. There would be an explosion of the numbers of persons diagnosed with mental disorders. We are not aware of any
data to suggest that, prior to 1980, when the BE was
first introduced, or in parts of the world that use the
ICD system for diagnosis, MDE is diagnosed more
or treated more than in those parts of the world that
rely on the DSM. On the contrary, European studies generally find similar depression prevalence rates
when DSM-IV and ICD-10 criteria are compared[35].
Results of epidemiologic population studies suggest
relatively manageable numbers. Using the National
Comorbidity Study (NCS), for example, 1,308 (16%)
of the 8,099 participants sampled met DSM-III-R criteria for MDE, including those who would be excluded by the BE[16]. One hundred fifty-seven of the
1,308 (12% of those with MDE and 2% of the total) experienced at least one BRD. Fifty-six of the
157 (4% of those with MDE and <1% of the total population) had DSM-III-R defined BRD. Even
fewer would meet DSM-IV criteria for BRD which
is more restrictive[15]. Similarly, Kendler et al.[17] reported only 23 participants out of a total sample of
9,242 individuals (0.25% of the total) in the Virginia
Twin Study of Psychiatric and Substance Use Disorders (VATSPSUD) had confirmed cases of BRD
that would be excluded by the DSM-III-R BE. Similarly, Gilman et al.[24] reported that only 0.5% of
the overall sample in NESARC data base met criteria for “bereavement-excluded depression,” hardly
suggesting an “explosion of the numbers of persons
diagnosed with mental disorders.”
2. Many BRDs are transient and remit on their own. Thus,
they should not be considered psychiatric disorders.[15] Although some BRDs do remit on their own, most of
the available data suggest similar rates of chronicity
and recurrence in BRD as in NBRD.[4, 18,30] Similar to other instances of MDE, BRD is often recurrent, genetically influenced, impairing, and treatment
responsive[4, 17]. These are all characteristics we associate more with MDD than with “normal sadness.”
The main issue here is whether one can identify which
depressive syndromes, early in their course, will become severe, chronic, or recurrent; and which will
spontaneously remit without complications. If those
depressive syndromes that occur in the context of bereavement are found to be more likely than NBRD
to be mild and self-limited, there would be some justification for the BE. However, we are not aware of
any clinical studies that compare the duration, course,
and consequences of BRD having all other features
of the BE (mild symptoms, minimal impairment, or
distress) with NBRD having the same features. It is
likely that many such depressions, whether or not occurring in the context of bereavement, are relatively
short-lived. Indeed, Posternak et al.[36] reported high
rates of recovery (40% within 8 weeks) in individuals
with recurrent MDD (presumably NBRD) even in
the absence of somatic treatment, and Perlis et al.[37]
found that 22% of patients with recurrent MDD
have episodes that last less than 3 months. There are
no clinical studies demonstrating that BRDs are any
more transient or benign than any other instances of
NBRD.
3. Since BRDs that are brief (≤2 months) and mild (no severe
dysfunction, morbid feelings of worthlessness, psychomotor
retardation, suicidal ideation) are similar to NBRDs that
are brief and mild on most validating features, all such
depressive syndromes should be excluded from the diagnosis
of MDE.[16] This is a separate issue and not germane
to the BE (see the discussion below regarding “mild”
conditions).
Depression and Anxiety
The Bereavement Exclusion and DSM-5 441
4. Severe depressions following bereavement already may
be diagnosed as MDE; it is only the mild conditions
that the BE disallows. Although that argument may
be partly true, it is largely irrelevant to the validity of the BE. Currently, MDE is a broad and heterogeneous category that includes a full spectrum of
episodes along several dimensions, including, but not
limited to, severity and duration, and also including a variety of subtypes.[38] Where on the spectra
of duration and severity the best cutoffs to define
“caseness” should lie is an important question, but
largely tangential to the issue of whether to continue the BE in DSM-5. In addition, the BE has
been with us for several years but remains a source
of confusion[12] and has not been reliably applied in
clinical settings. As presently applied, the BE appears
to exclude individuals from diagnosis and treatment
who may be at risk for serious consequences of untreated MDE.[19] This is because the DSM-IV allows
the BE to be “overridden” only if certain features indicating severity are present: marked functional impairment, morbid feelings of worthlessness, severe
psychomotor retardation, psychosis, and suicidality,
which are not empirically validated. However, there
are many other ways in which a recently bereaved
person’s BRD may be severe: for example, profound
anhedonia, unrelenting fatigue, or pronounced agitation. Bereaved individuals with these features would
not be given a diagnosis ofMDE under current DSMIV guidelines and could be deprived of much needed
treatment.
5. Removing the BE medicalizes a normal condition,
grief.[39, 40] This is not true. MDE and grief are fundamentally different constructs. The former is a medical
condition that is life threatening and often requires
treatment; the latter is thought to be an adaptive, instinctual response to loss that generally does not require treatment[27, 41]. Although bereaved individuals
may feel terribly sad and like “a piece of themselves” is
missing, most do not experience MDE. But just as in
the context of any number of other serious life adversities, some bereaved individuals do experience MDE.
When that happens, the individual may simultaneously experience grief and MDE. But acknowledging
that bereavement can be a severe stressor that may
trigger an MDE in a vulnerable person does NOT
medicalize or pathologize grief![42] Rather, it prevents MDE from being overlooked or ignored and
facilitates the possibility of appropriate treatment.[34]
Furthermore, removing the BE does NOT imply that
grief should end in 2 months. Indeed, for many individuals, grief lasts for months, years, or even a lifetime
in its various manifestations,[27, 43] whether or not it
is accompanied by MDE.
6. Because criteria for “complicated” or “prolonged” grief require a longer time period for diagnosis than MDE (6
months versus 2 weeks), it may be that someone early in
the process of “complicated grief disorder” would be mistakenly diagnosed with an MDE were the exclusion removed. This would put them at risk to receive inappropriate treatment. Research has shown that “complicated
grief” can be distinguished from MDE.[27, 44] The
core symptoms of complicated grief—yearning and
preoccupation with the deceased—are not typically
seen with MDE. People with complicated grief get
lost in reveries; engage in compulsive proximity seeking related to the deceased; and strive to avoid experiences that trigger reminders of the loss. None of these
are symptoms of MDE. Nor are pervasive dysphoria and other depressive symptoms characteristic of
MDE core components of complicated (prolonged)
grief. However, about 30% of community samples
with complicated grief have co-occurring MDE, and
as many as 80% of clinical populations of individuals
with complicated grief may have current or past histories of MDE.[33, 45] In addition, MDE is a risk factor
for the development and/or persistence of complicated grief,[27] and treating MDE relatively early in
the course of bereavement has been shown to facilitate a “normal” grief process,[46] perhaps also protecting against the later development of complicated
grief.[47] Thus, it is important for clinicians to diagnose MDE, even (or maybe especially) in the context
of bereavement, so that informed decisions regarding
treatment may follow.[33]
7. Since there is so much symptomatic overlap between grief
and MDD, it is virtually impossible to make an accurate
diagnosis of MDD in someone who is acutely bereaved.
Regardless of whether a depressive syndrome is triggered by bereavement or by other life events, differential diagnosis can be a challenge, particularly if the
depressive syndrome is relatively mild and brief, but
that does not mean that it should not or cannot be
made.[34, 41,42] The challenge is no less important or
manageable than the challenges of diagnosis in persons with depressive symptoms and dementia[48] or
physical illness.[49]
8. Removing the BE will “provide fodder to a skeptical public who suspects that a main goal of the DSM-5 is to
increase business for mental health professionals and provide increased profits for the pharmaceutical industry.”[13]
There will no doubt be skeptics who make that
claim. However, that misperception is best addressed
by educating mental health providers, primary care
physicians, and the general public about depression
and its treatment.[12, 42] Decisions about criteria for
mental illness should be based on the best available research data. It also is important to note that the diagnosis of MDE does not necessarily lead to a prescription for antidepressants. Rather, each unique person
and situation should be assessed. As in other circumstances, factors that go into the decision of whether,
when, and how to treat include past history of depression, current support and resources, severity and
duration of symptoms, suicide risk, comorbidity, past
responses to treatment, and patient preferences—
whether or not the person is recently bereaved is but
one very small factor in the treatment algorithm.
Depression and Anxiety
442 Zisook et al.
The major limitation of this review is that so few studies have been designed to systematically examine depressive syndromes restricted to the first 2 months after bereavement, the period identified by the DSM to exclude
the diagnosis of MDE, who do and do not meet the
specific criteria for BE outlined by the DSM. The ideal
study to test the validity of the BE would be a prospectivestudy simultaneously comparing individuals who: (1)
meet symptomatic criteria for MDE beginning less than
2 months after the death of a loved one, who do, and do
not, have the severity and impairment features specified
by the DSM-IV BE criteria; and (2) MDEs of similar
duration, severity, and impairment whose onset is unrelated to the recent death of a loved one, who do, and do not,
meet the same criteria. Unfortunately, we found no such
studies in the literature. A second limitation is that the
ratings of whether each validator favors one or the other
hypothesis were made by one investigator (SZ) and are
inherently subjective. Although most of the decisions are
obvious, such as when the validators are equally likely to
occur in BRD and NBRD or when the difference is in
the direction or BRD being milder, less likely to recur,
or more benign than NBRD, some of the ratings are
more complex and subject to rater bias. For example,
Corruble et al. found the group that was excluded from
the diagnosis of MDE on the basis of the BE had more
previous episodes of MDE than participants diagnosed
with MDE[19] and also had more severe episodes with
more suicidal ideation than those diagnosed with MDE
without bereavement[21]. In each of these instances, the
rating was H.1./H.2., reflecting that the validator did not
clearly support one hypothesis over the other.
SUMMARY AND CONCLUSION
After the death of a loved one, grief almost always
occurs, and with it, sadness and other depression-like
symptoms are common. Less common, the death of a
loved one may precipitate a full MDE. When this happens, the MDE generally appears soon after the loss as
an unwelcome companion to the bereaved’s grief and the
individual faces the double burden of grief and MDE.
This review addresses the question of whether a full
MDE in the context of bereavement-related grief is substantially different fromMDE unrelated to bereavement.
Most of the data we reviewed suggest the answer is no.
BRD and MDE occurring in any other context
(NBRD) share several clinically relevant characteristics.
Both are genetically influenced and most likely to occur in individuals with past personal and family histories of MDE. Both share similar personality characteristics, patterns of comorbidity, and, at least in some
studies, the likelihood of chronicity and/or recurrence.
Furthermore, compared to bereaved persons who may
be in great pain but who do not meet MDE criteria, bereaved persons with MDE suffer more; are more likely
to feel worthless and have suicidal ideation for months
to years; have poorer general medical health and worse
interpersonal and work function; experience biological
perturbations associated with MDE; have a worse prognosis; and may be at risk for particularly intense and
prolonged grief reaction.[27, 50,51] Finally, the major depressive syndromes associated with bereavement—like
MDE in other contexts—often respond to antidepressant medications.[4, 20,21, 52]
In short, BRD is not like normal grief, but is like any
other MDE in most important respects. Thus, the predominance of data previously reported[4, 5] along with
the newer data reviewed here supports Hypothesis 2—
BRD is not fundamentally different than NBRD—and
suggests that the BE should not be carried over to DSM5. Eliminating the BE is not meant to “medicalize” grief;
but rather to facilitate accurate diagnosis and appropriate treatment for those bereaved individuals who also are
suffering from an episode of major depression.
Acknowledgments. This work was supported
by National Institute of Mental Health grant
R01MH085297 and a grant from the American
Foundation of Suicide Prevention.
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Depression and Anxiety
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