Validity of the bereavement exclusion to major depression: does the empirical evidence support the proposal to eliminate the exclusion in DSM‐5?

The DSM-5 Mood Disorders Work Group has proposed eliminating in DSM-5 the major depression criterion E, “bereavement exclusion” (BE), which recognizes that depressive symptoms are sometimes normal in recently bereaved individuals 1,2. This proposal has become one of the more contentious issues regarding the DSM-IV revision 3,4,5,6,7,8,9. Those favoring the BE's elimination argue that the empirical evidence demonstrates the BE's invalidity and supports its removal. For example, Zisook et al 10, reviewing studies “that bear on the validity of the ‘bereavement’ exclusion”, conclude that “the preponderance of available data suggests that excluding recently bereaved individuals from the diagnosis of MDE… may no longer be justified”; and Lamb et al 11 assert that, since Zisook et al's review, “four other studies have been published that provide further evidence supporting the removal of the bereavement exclusion”. In this review, we examine whether these claims are justified. We evaluate the quality of the evidence put forward in the cited reviews, and also examine some more recent evidence bearing on the validity of the BE. Based on our results, we offer some recommendations for DSM-5. Prospective studies of bereavement 12,13,14 have demonstrated what physicians have long known 15,16, that normal grief frequently includes depressive symptoms such as sadness, difficulty sleeping, decreased appetite, fatigue, diminished interest or pleasure in usual activities, and difficulty concentrating on usual tasks. A considerable number of individuals reach the 5-symptoms-for-2-weeks level that satisfies diagnostic criteria for major depressive disorder (MDD), and many experience clinically significant distress or role impairment due to their grief. Yet, their bereavement-related depression may resolve over time without treatment and may not have the chronic and recurrent course seen in MDD. The overlap of symptoms between intense normal grief and MDD creates a potential false positive problem in which depressions that are part of normal bereavement may be misdiagnosed as MDD. Excluding all bereavement-related depressions from MDD diagnosis is no solution. Severe emotional stressors such as bereavement can trigger genuine MDD 17. Consequently, the diagnostic challenge is to distinguish those bereavement-related depressions that are likely intense normal grief from those that have turned into pathological depressions. The BE, which has been in the DSM in varying forms since 1980, offers the clinician guidance in making this difficult discrimination. It excludes bereavement-related depressions from MDD diagnosis only when they are “uncomplicated”, that is, they manifest certain duration and symptom features more consistent with normal grief than with mental disorder. The BE first specifies that, to be included in MDD, a depression must “not be better accounted for by bereavement”. That is, the clinician is asked to compare two rival hypotheses regarding the patient's depressive feelings, MDD versus depressive symptoms that are part of normal grief. The BE goes on to operationalize what features would suggest the depression qualifies for the diagnosis of MDD. If the depressive episode either lasts longer than 2 months or includes at least one of a series of features that are uncharacteristic of normal grief (i.e., marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation), then the episode should be diagnosed as MDD. Conversely, if the episode resolves within 2 months and does not include any of the uncharacteristic features, then it is consistent with normal grief and is excluded from the MDD diagnosis. The “rationale” section on the DSM-5 website's major depressive episode page explains that the reason for eliminating the BE is that “evidence does not support separation of loss of loved one from other stressors” 18. The website cites only one reference as the basis for this proposal, a review paper by Zisook and Kendler 19 that claims that bereavement-related depressions are generally similar to standard depression. Zisook and Kendler ask: “Is bereavement-related depression the same or different from standard (non-bereavement-related) major depression?”. To answer this question, they compared bereavement-related depression to “standard” major depression following other triggers or no triggers. They evaluated whether the two conditions are similar or different on a variety of variables divided into antecedent, concurrent, and predictive “validators”, including demographic variables, family and past personal history of major depression, health and social support, associated clinical features, biological factors, persistence, and response to treatment, and claim they are similar on most validators. “Similarity” was not precisely defined, but seemed to be understood as having significant relationships to a variable in the same direction. Given that the bulk of standard major depression is clearly disordered, if bereavement-related depression and standard major depression share enough “validators”, this was taken to imply they are likely the same pathological condition. However, in terms of assessing the BE's validity, there is a fatal flaw to this review. Comparing all bereavement-related depressions to all standard major depressions has little to do with the evaluation of the BE. The point of the BE is to distinguish between excluded “uncomplicated” likely-normal bereavement-related depressions versus non-excluded likely-disordered ones. The BE implies at most only that excluded bereavement-related depression is different from standard major depression; the BE declares non-excluded bereavement-related depression to be pathological. Combining the two bereavement-related depression groups and finding similarity to standard major depression does not test the BE. Zisook and Kendler acknowledge the problem. They note that an evaluation of the BE must distinguish between those “who are considered by the DSM-IV-TR to be experiencing normal bereavement” and those “whose symptoms are so severe or persistent that the DSM-IV-TR recommends considering the diagnosis of a true major depressive episode rather than just normal bereavement”, and that their review largely fails to meet this requirement. In comparing all bereavement-related depressions, most of which the BE labels MDD and not normal grief, to standard major depressions, it is hardly surprising that Zisook and Kendler find similarity across a range of validators. A subsequent review attempted to overcome these difficulties and to specifically evaluate the validity of the BE. Zisook et al 10 acknowledge the weakness of the earlier review, focusing on its failure to observe the BE's duration requirement: “Since most of the studies reviewed did not describe or follow individuals with bereavement-related depression specifically within the first two months of bereavement (the period of time the DSM-IV-TR demarcates as excluding a diagnosis of major depressive episode), we were unable to draw definitive conclusions about the validity of the bereavement exclusion”. Zisook et al cite no new evidence, and conduct the same type of “similarity” analysis using the same variables as in the earlier review. However, they attempt to fix the problem with the earlier review by focusing on studies of depressive syndromes evaluated during the first two months of bereavement, referred to here as “early-phase bereavement-related depression”, which they consider directly relevant to assessment of the BE. Finding many similar relationships to validators, they conclude that the BE “is not valid because, using validating criteria, bereavement-related depression within the first two months after the death of a loved one resembles non-bereavement-related depression”. Here, as in the earlier review, the concept of similarity remains fuzzy. Does “similar” mean that correlations must be of comparable size? Sometimes it seems so, with relationships declared to be “virtually identical”. Or, does “similar” just mean that correlations must be in the same direction, even if very different? Few quantitative comparisons are made, so in effect the latter, weaker approach is taken. Despite the authors’ claims to the contrary, in fact the Zisook et al review 10 offers no more support for the BE's invalidity than did the earlier one 19. Throughout the paper, from the title (“Validity of the bereavement exclusion criterion for major depressive episode”) to the conclusion, the paper is framed as though it is reviewing studies pertinent to the BE's validity. A careful examination however reveals that not one of the cited studies actually examined cases that satisfy the BE. The BE's duration limitation, that excludes episodes which end by ≤2 months, and its requirement that excluded episodes lack the three uncharacteristic symptoms are its “core features”. Yet, not one study cited by Zisook et al applies either the duration or symptom requirements to the studied group. Consequently, they, too, examined mixed groups of BE-excluded and (mostly) non-excluded bereavement-related depressions. Again, it is unsurprising that correlations with validators are in the same direction as standard major depression. Instead of the BE's 2-month duration limitation for exclusion, the Zisook et al review substitutes the “early-phase” requirement that the bereavement-related depressions in a study must be assessed prior to 2 months post-loss, no matter what their ultimate duration. From a duration perspective, these cases satisfy the BE only provisionally. Some of these cases will resolve within two months and thus ultimately meet the BE's duration limit. Many others, however, will continue for far longer than 2 months and thus ultimately not meet BE criteria, and would be classified as true MDD cases. After all, every bereavement-related depression, excluded or non-excluded, has an early phase. Thus, including cases based on their being evaluated within the two-month window rather than resolving within two months creates a mixed group of cases, some of which (in retrospect) will meet the BE whereas others will not. The Zisook et al review thus repeats in altered form the central error of the Zisook and Kendler review of attempting to draw conclusions about the similarity of BE-excluded bereavement-related depressions to standard major depressions from studies of mixed groups of bereavement-related depressions that mostly consist of non-excluded cases classified by the BE as pathological. Zisook et al acknowledge that their samples mix together excluded and non-excluded bereavement-related depressions: “Early bereavement-related depression, as conceptualized in this paper, is likely a mixture of cases including: those with “bereavement” as defined by the DSM-IV; those that start out with DSM-IV “bereavement” and evolve into true major depressive episode”. However, they fail to recognize that this undermines any claim to showing BE invalidity. The other core BE requirement for exclusion is that the episode does not include the so-called “uncharacteristic symptoms” (i.e., suicidal ideation, a sense of worthlessness, or psychomotor retardation). The Zisook et al review completely ignores this component of the BE criterion, taking the duration requirement (in the mistaken form considered above) as an adequate approximation to the BE. Yet epidemiological evidence suggests the symptom criteria are important independently of duration as determinants of whether the BE is met. For example, in the National Comorbidity Survey, of all those who reported bereavement-related depressions that lasted a total of 2 months or less, only 50% qualified for the BE; the other 50% manifested one or more symptoms disqualifying them from exclusion (Wakefield and Schmitz, unpublished analysis). In sum, although Zisook et al claim to establish the invalidity of the BE, not one of the studies they cite applied the BE's duration or symptom criteria. The reviewed articles are essentially irrelevant to claims about the BE's validity. The Zisook et al review offers no support for the utility of the selected validators in distinguishing between normal distress and mental disorder. If excludable bereavement-related depressions and standard major depressions are similar in their correlations to a validator, that proves nothing about the disordered nature of the excluded bereavement-related depressions if the validator itself tends to correlate both with disorder and normal distress. For example, the fact that larger percentages of women than men have both standard major depressions and excluded bereavement-related depressions (assuming that would be shown in an examination of legitimate studies of excluded bereavement-related depressions) could just mean that women with more emotional both in and disorder. biological variables such as and in a variety of disordered and normal even for major and thus are not enough to standard major depression or to disorder to suggest any about whether bereavement-related depressions are some of Zisook et al's more validators of 10 are to the BE criteria in that their as validators For example, their of (i.e., of and psychomotor and of bereavement-related depressions as validators no sense because, by BE-excluded cases have suicidal of and psychomotor and past 2 the of the DSM-5 Mood Disorders Work in reviewing proposed treatment response as the reason for eliminating the BE, Zisook and Kendler who in based their claim completely on a study by Zisook et al In this bereaved individuals DSM-IV MDD criteria about 2 months were with for 2 a of on Given the and the fact that Zisook et al's study no group in a diagnostic with response the are to that studies that without treatment bereavement-related depressions have in symptoms after 2 months post-loss, the is consistent with the course of if bereavement-related depressions should to it is treatment response would be a reason for considering a that many normal conditions to Some of eliminating the BE the of in excluded bereavement-related depressions. For example, Zisook et al 10 cite a study showing an of in MDD those without et al in considering the BE, note that “bereavement may the of and the of early This was also by Zisook in a National in which is as rather the of who may not be than the diagnosis of depression, not and having that Some bereaved individuals do attempt whether or and cases can in many However, cases excluded by the BE by lack suicidal is no evidence for in excluded bereavement-related depressions, and evidence suggests the For example, those individuals who only bereavement-related depressions in the National Comorbidity not one reported a attempt (Wakefield and Schmitz, unpublished The study Zisook et al cite to establish in those without has as many pathological with prior a irrelevant to by individuals with excluded bereavement-related depressions. In a review published in Lamb et al 11 that studies published since the earlier support the BE's invalidity. Some of the studies they cite do examine BE-excluded cases. We of the cited et al the to compare MDD following bereavement versus other stressors or no They reported that bereaved did not from the other two groups on However, they did not BE-excluded cases. of the were and were to have treatment for at least a making it that many were BE-excluded cases. as be in a largely of the out of suicidal ideation, suicidal for BE In sum, the study does not examine BE-excluded cases and does not the BE's validity. et al claim to study BE-excluded cases diagnosed by but the BE was In this and other studies this group showing that BE-excluded cases are as or more severe than standard MDD and non-excluded bereavement-related depressions across a variety of features, from symptom and treatment response to impairment, that the BE should be claims the of the BE, which is to severe cases and with from earlier empirical studies comparing excluded to non-excluded bereavement-related depressions In of et al's reveals that the so-called BE-excluded cases did not in fact meet the BE The study for example, that of excluded bereavement-related depressions manifested psychomotor worthlessness, and suicidal Yet, such symptoms an episode from BE Thus, it that the of BE-excluded individuals did not for The likely for this is et al asked physicians to whether were excluded by the BE without any or then those at without validating that they were the were most likely they were by the BE's one of the frequently when for the for DSM with MDD criterion to what they Consequently, the et al are not based on a true BE-excluded and are not to any to which the BE is The thus have no for the evaluation of the BE's validity. they that the BE's is to and likely studies cited by Lamb et al do examine samples of BE-excluded cases that satisfy both core BE criteria. et al's study of depression to no significant in between the cases of bereavement-related depression and standard MDD However, the one must with et al's that “the number of DSM-IV excluded episodes was to for to may also have the of normal and disordered distress to a that true further et al compared excluded to non-excluded bereavement-related depressions in the National Comorbidity They that the on the validators of symptoms, depression, duration of symptoms, with and three the validity of the BE. However, that some validators were to the features of episodes to provide the validators with and are to the BE and Thus, the the demonstrated were due to these and in effect have some although they do not all the validators. the were actually for the can be but no study has attempted such an analysis as of this so the of the et al study for BE validity Kendler et al compared bereavement-related depressions and standard major depressions on a range of validators in a of evaluated for depression at over 10 they did BE-excluded they did not compare excludable bereavement-related depressions to bereavement-related depressions or standard major depressions in they examined the between excluded bereavement-related depressions and standard major depressions is, standard major depressions the BE's duration and symptom criteria for The for this of was that the DSM such standard major depressions as so if excluded bereavement-related depressions are similar to excluded standard major depressions which both their study and et al they are they must be they that the exclusion of bereavement-related depressions but not standard major depressions is an that must be by the BE However, the over whether the BE is valid must be from the of whether depressive to other stressors such as or loss are considered or should be excluded from MDD as To the question, the and between excludable standard major depressions and other standard major depressions would have to be a Kendler et al do not in their The of the BE was based on an evaluation of the evidence that bereavement-related depressions are sometimes not MDD, whereas the of other episodes within MDD without evaluation and is not by the BE. In any the effect of the Kendler et al was that they did not their data in a that directly bear on BE validity. In sum, three of the studies cited by Lamb et al do the BE criteria to a However, for varying of the three offer evidence for or the validity of the BE. the validator with the most validity in the between excluded bereavement-related depression and standard major depression is of depressive is a of depressive episodes in individuals from standard major depression, whereas in normal emotional one would is not a BE criterion, so it can be to compare excluded bereavement-related depression versus standard major depression without the recent using the National on and is the first to compare standard major depression in a and compared the of depression during a period in who at BE-excluded depressive those who other of depressive and those with no history of depression. that who at a bereavement-related depression were no more likely to have an MDD episode over a period than were those in the who no history of MDD at In who either standard major depressions, standard major depressions, or recurrent MDD, and than those without a depression history or those with BE-excluded that “the support the DSM-IV bereavement exclusion criterion for major depressive episodes in the and attempted to in the They compared depression at 2 in excludable bereavement-related depression; standard major depression; standard major depression; and no history of depression. The BE-excluded was not different from the in the group but and than for and standard major depression and using a different data and supporting and the for the BE's validity. The and the and studies the central for BE that there is no evidence that bereavement-related depression in course from standard major depression. the does not support the invalidity of the BE or its elimination from there are some that could its validity and its In epidemiological or when a patient's the duration of bereavement-related depressions may be known However, in clinical bereaved experiencing depressive symptoms for than 2 months must be diagnosed long the episode will The BE's duration and symptom criteria for the will the depressive symptoms 2 months, or one or more uncharacteristic symptoms a diagnosis of are in DSM-IV of diagnostic criteria on the resolving some the diagnosis if the the If a diagnosis must be that has been the diagnosis must be due to lack of whether the will resolve within the For example, to the DSM-IV-TR disorder that episode of the lasts at least but than If the symptoms longer than months, the diagnosis is For who with symptoms of more than and than the clinician is to the diagnosis as it is not known whether the symptoms will resolve within the If then the diagnosis would be from disorder to The of the section that this diagnostic applies to any which diagnosis on the duration of Thus, for example, intense are in the DSM specifies that a can be diagnosed as a only if it lasts for at least Consequently, a with intense of of 2 duration must be diagnosed as with to establish whether the past months and thus qualifies as a The diagnosis of excluded bereavement-related depressions evaluated after loss of a loved one this that the duration be or less, but the clinician must the diagnosis it is known whether the symptoms will resolve by Thus, following DSM-IV it would be to the for cases of excluded bereavement in which depressive symptoms are The of will to the clinician that a definitive diagnosis on the of more in this a of whether the depressive symptoms have by the point without of uncharacteristic This could some false that due to about the diagnosis. In the whether bereavement-related depression symptoms are better as MDD or normal grief, an in BE criteria that would genuine cases would be to into the criteria the requirement that past history of MDD a bereavement-related depression for with a past MDD history have a to MDD that be the severe of experiencing the loss of a loved The suggests that, those experiencing an bereavement-related depression, past MDD history persistence, severe symptoms, and This variable is enough that to past history For example, in Zisook and study of the course of bereavement, individuals DSM MDD criteria by 2 months post-loss, and of were at months and considered However, individuals MDD criteria at 2 months a history of prior MDD, and individuals MDD criteria at months also such a those are the same then if individuals with prior MDD been from the group to which the BE be applied at 2 months, the false based on duration would have from to We thus that a personal history of MDD should BE the studies by et al which to support the elimination of the BE, in fact the BE is to and by not specifically in its of the problem likely from the The could be to the of such a point for we offer the following of criterion E, If the episode in the of bereavement, it at least one of the following features of major depression rather than normal duration than 2 suicidal morbid preoccupation with marked psychomotor and marked functional psychotic or a history of major depressive disorder in other than depressive episodes that have of these features should be a diagnosis of bereavement-related depression, these there are many that be about to the validity of the BE. For example, should the 2-month duration for be based on recent evidence that validity may be at the uncharacteristic symptoms impairment a should similar to other stressors be within an BE to a further evidence for their However, the of whether there is empirical evidence that the BE is can be The claim that there is such evidence is based on of the and has no basis in Consequently, there is no basis for the bereavement exclusion from the DSM-5.