Sidney Zisook, MD

“The risk of love is loss and the price of loss is grief. But the pain of grief is only a shadow when compared with the pain of never risking love.” — Hilary Stanton Zunin

The figurative and literal losses associated with the COVID-19 pandemic are profound. These losses highlight the need for mental health professionals to gain sophistication in understanding, recognizing, and approaching grief in all its myriad forms in the clinical setting. The term “grief” describes the emotional, cognitive, functional, and behavioral responses to a meaningful loss. Throughout life, individuals face a number of losses capable of triggering grief. These include, but are not limited to, loss of their youth, opportunities, functional abilities, health, jobs, and meaningful relationships.

Bereavement is a nearly universal phenomenon, often experienced many times throughout life. Of all the events and stressors in ordinary life, bereavement may have the most powerful impact. Yet, bereaved individuals, their family and friends, and even mental health clinicians often are perplexed about its nature, course, and prognosis. In this article, we describe key characteristics of the acute grief response, the natural transition to integrated grief, and 2 related conditions that often require clinical attention: prolonged grief disorder (PGD) and major depressive disorder (MDD). PGD is a condition that occurs when the transition from acute to integrated grief is derailed. Meanwhile, MDD, a mood disorder that is not necessarily linked to grief, may be precipitated or exacerbated by meaningful losses, including bereavement.

. Bereavement usually triggers an acute grief response. Although not unique in all respects, some aspects of grief following bereavement are distinctive. As death is final and irreversible, bereaved individuals often experience their grief with a sense of helplessness and disconnection. The hallmark of acute grief is the intense focus on thoughts and memories of the deceased individual, accompanied by sadness, yearning, and longing. Acute grief is not a linear process with concrete stages or boundaries. Rather, it is a composite of overlapping and fluid cognitions, emotions, and behaviors that vary across individuals and even in the same person after different losses and over time.

 The experience of grief is influenced by social, religious, and cultural norms as well as by age, health, ethnic identity, coping style, attachment style, circumstances of the death, prior losses, and available social support and material resources.2 Yet, despite the variation and individual nuances, there are some common features and challenges of acute grief that many bereaved individuals face.

First are frequent strong feelings of yearning and sorrow. These are powerful feeling states, generally occurring in periodic waves of intense emotional distress that are often accompanied by somatic discomfort. These feelings may include a wrenching of the gut, shortness of breath, chest pain, lightheadedness, weakness, rapid welling up of tears, and uncontrollable crying. During the early days and weeks, these responses tend to erupt often, suddenly, and unexpectedly. Over time, their occurrences tend to be increasingly tied to specific thoughts and reminders of the deceased. As a result, their frequency and intensity diminish.

Second is a mixture of other feelings (positive and negative). Some common challenging thoughts, emotions, and experiences include: a sense of disbelief; intrusive thoughts and images focused on the deceased; decreased interest in ongoing life; feelings of insecurity, emptiness, loss, anger, guilt, anxiety, and loneliness; feeling overwhelmed or helpless; and varying degrees of distractibility, poor concentration, confusion, forgetfulness, or lack of clarity and coherence. Yet, even during acute grief, these painful experiences often are intermingled with positive feelings. For example, a grieving individual may experience warmth, amusement, or pride when thinking about their loved one and recollecting tender and/or humorous memories. There can be a sense of relief at the end of suffering. Depending upon the grieving individuals’ beliefs about death and the afterlife, they may feel joy, peace, and contentedness alongside the more painful feelings and thoughts.

. Although grief following bereavement is painful and associated with emotional and somatic distress, most individuals adapt to their loss, find a way through the acute grief period, and ultimately continue with their lives without professional assistance. Mourning is the process of adapting to loss, and this process can transform acute grief into what we call 

 Adaptation entails coming to grips with the reality, permanence, and consequences of the loss; establishing a new relationship with the deceased through memory and deeds; and looking forward to a future where life can be meaningful and joyful, even without the deceased. When mourning is successful, the painful and disruptive experience of acute grief transforms into an experience of integrated grief that is bittersweet but no longer all consuming. In integrated grief, individuals who are bereaved recognize what the loss has meant to them and that they are once again capable of experiencing happiness and meaning. They are thus able to shift attention from their loss to the world around them.

ICD-11 and DSM-5-TR Criteria for Prolonged Grief Disorder

. For a meaningful minority of grieving individuals, perhaps as high as 7% to 10%, the natural transition from acute to integrated grief is forestalled.

 For these individuals, maladaptive thoughts, feelings, and/or behaviors derail both adaptation to the loss and restoration of a life with meaning, joy, and purpose.

 Instead, the agony, yearning, and preoccupation with the loss remains intense and debilitating. This state has been formally recognized by both the ICD-11 and DSM-5-TR as “Prolonged Grief Disorder” 

); in the past it was often called complicated grief (CG), and it was called persistent complex bereavement disorder in the DSM-5.

 The distinguishing characteristics are persistent and intense grief that lasts well beyond the period expected by social and cultural norms (6 months in ICD-11 and 1 year in DSM-5-TR) and results in impairments in daily functioning. Many of the features noted in the acute grief section above, in a heightened state, characterize PGD, with the key difference being their persistent intensity without a substantial trajectory toward adaptation to the loss. In brief, healing is stalled and bereaved individuals who have PGD appear figuratively frozen in grief.

PGD may follow the loss of any close relationship but occurs more often in parents who have lost a child and after the death of a spouse or romantic partner.

 It is more likely when the death is unexpected, sudden, or violent, such as after suicide, homicide, or an accident.

 Multiple factors appear to increase the risk of PGD, including depression, anxiety disorders, current substance use/abuse, multiple losses, particularly stressful circumstances surrounding the death, lack of social supports, uncertainty about the death, and the unavailability of usual mourning rituals.

Psychotherapy is the treatment of choice for PGD. A focused, manualized form of psychotherapy has been found to be robustly effective in 3 separate randomized trials.

 The primary goals of this grief focused therapy are to identify and resolve processes that derail adaptation and thereby get in the way of acute grief transforming into integrated grief. In our experience, PGD often remains undiagnosed and/or is misdiagnosed as MDD. However, in each of the studies noted above, participants treated with psychotherapy more specific to depression

 or antidepressant pharmacotherapy3 did not respond nearly as well as those treated with the grief focused therapy. In the latter study, antidepressant medication, either alone or in combination with psychotherapy, was not found to alleviate grief, but antidepressant medication demonstrated some promise for decreasing depressive symptoms when given along with the therapy.

When formal therapy for PGD is not available, there is still much the clinician can do. The first step is to include an inquiry about bereavement as part of all initial evaluations and to have an open ear for issues related to grief in ongoing clinical management. Questions to help identify and guide the inquiry include: Has anyone close to you died? If so, have you been able to grieve and adjust to life without him/her? Are you still struggling with your loss in any way? Do you mind if I ask you more about it?

If the answers suggest an issue with grief, the next step is to invite an open inquiry into the relationship, death, mourning process, and impact of the loss. Supportive, nonjudgmental, empathic communication can let patients know they are not alone and can aid in the healing process. Other components of grief-informed clinical management include monitoring symptoms, letting the patients know you are there for them, and providing gentle encouragement for re-engaging in daily activities.

 In addition, optimizing treatment of cooccurring conditions and providing information about available support resources, such as the Center for Complicated Grief website and the American Foundation for Suicide Prevention website for suicide-loss survivors, can be invaluable. Left untreated, PGD is a debilitating and often chronic condition. Recognition and proper intervention can be life promoting and, in some cases, life saving.

The relationship between depression and bereavement is complicated and often perplexing to even the most seasoned clinicians. Based largely on Clayton’s pioneering studies on the relationships between grief and depression,

 the DSM-III introduced the Bereavement Exclusion (BE) for the diagnosis of MDD.

 This was meant to protect against grief being mistaken for depression, mislabeled as an illness, pathologized, and/or inappropriately treated. The BE disallowed the diagnosis of MDD during the first 2 months of bereavement unless the depressive symptoms and dysfunction were particularly severe, defined by symptoms of morbid worthlessness, psychomotor retardation, suicidal ideation, psychotic features, or marked disability.

The BE was subsequently eliminated in the DSM-5, as the DSM-5 mood disorders task force concluded it had become a roadblock to the diagnosis and treatment of MDD.

 Instead, the revised diagnostic criteria for MDD included a note that promoted the use of clinical judgment “based on the individual’s history of the cultural norms for the expression of distress in the context of loss” and provided guidelines to help differentiate MDD from grief that is not complicated by co-occurring MDD.

For example, in grief the predominant affect is emptiness and loss as opposed to the persistent depressed mood and anhedonia of MDD. In grief, the dysphoria decreases in intensity over days to weeks and occurs in waves that are associated with thoughts or reminders of the deceased. In contrast, with MDD, the dysphoria tends to be persistent and is not tied to specific thoughts or images. Grief is characterized by a preoccupation with thoughts and memories of the deceased, whereas in MDD the preoccupation is with self-critical or pessimistic ruminations. Similarly, self esteem is preserved in grief, while feelings of worthlessness predominate one’s self-view in MDD. Thoughts of death and dying in grief are generally focused on the deceased and possibly about joining or reuniting with the deceased loved one, while thoughts about dying in MDD more often are focused on ending one’s life in the setting of feeling worthless, undeserving of life, or unable to cope with the pain and misery of depression.

 In contrast to the experiences of those with MDD, bereaved individuals often retain the capacity to laugh, to appreciate the comfort and support of relatives and neighbors, to be consoled, and to recognize that what they are going through will lessen in time (

But the key question may not be one of either/or. Rather, knowing that bereavement triggers grief in most, and MDD in some, changes the question from whether a bereaved individual is grieving or depressed, to whether they are grieving and experiencing cooccurring MDD. Changing the question in this way may open the door to prompt diagnosis and treatment when indicated.

The importance of appreciating both the uniqueness and confluence of these conditions is underscored by several factors. MDD is a risk factor for developing PGD as well as a potential consequence of the death of a loved one in an individual already predisposed to MDD. Studies have confirmed high rates of both past and current MDD in bereaved individuals with PGD.

 While research on the influence of MDD on the severity or treatment outcome of PGD is sparse, the collective clinical experiences of the authors of this article suggest an adverse effect on intensity, duration, function, and treatment response of PGD in direct proportion to the severity of the cooccurring depression. Furthermore, while the only systematic, large, randomized controlled study on the effects of antidepressant medications for PGD did not demonstrate an effect of antidepressants on grief symptoms, it did suggest antidepressants relieved symptoms of depression in participants who also received grief-focused psychotherapy, and only in those.

More is known about the effects of PGD on MDD. In a large multisite study of treatment resistant MDD, a surprisingly large proportion of the patients had symptoms of PGD, which had not been noted in the clinical charts and had not been the focus of any treatments. Importantly, those with symptoms of PGD had more severe depression, increased suicide risk, and were significantly less likely to respond or remit to treatment.

Clinicians must carefully distinguish between grief, PGD, and MDD. A disorder that can occur when the natural grieving process is derailed, PGD is a painful and debilitating condition that can last for years in the absence of PGD-focused treatment. For PGD, the treatment of choice is either providing evidence-based PGD therapy or making a referral to a grief specialist. The aim is to provide support for healthy lifestyle and activities while also treating potential co-occuring conditions. If a bereavement specialist is not available, grief-informed clinical management can be enormously helpful. It is the authors’ hope that the guidance delineated in this article allows for a more refined, therapeutic approach to grief in various clinical settings—an approach that is especially relevant during this unique time in history when themes of loss and grief are so salient and pervasive.

is a resident in psychiatry at the University of California, San Diego.

 is an associate clinical professor in the department of psychiatry at the University of California, San Diego.

 is distinguished professor in the department of psychiatry at the University of California, San Diego.

Learn more about grief from Dr Iglewicz or mood disorders from Dr Zisook, please join us for the 

Annual Psychiatric Times World CME Conference

 September 30, 2021 through October 2, 2021. 

1. Shear K, Reynolds C, Simon N, Zisook S. Grief and bereavement in adults: clinical features. UpToDate. 2017. Accessed August 27, 2021. 

https://www.uptodate.com/contents/grief-and-bereavement-in-adults-clinical-features

2. Zisook S, Simon NM, Reynolds C, et al. Phenomenology of acute and persistent grief. In: Simon N, Hollander E, Rothbaum BO, & Stein D J, eds. 

The American Psychiatric Association Publishing Textbook of Anxiety, Trauma, and OCD-Related Disorders

, 3rd ed. American Psychiatric Association Publishing; 2020:557-570.

3. Shear MK, Reynolds CF 3rd, Simon NM, et al. Optimizing treatment of complicated grief: a randomized clinical trial. 

4. Zisook S, Shear K. Grief and bereavement: what psychiatrists need to know. 

5. Kersting A, Brähler E, Glaesmer H, Wagner B. Prevalence of complicated grief in a representative population-based sample. 

6. Lundorff M, Holmgren H, Zachariae R, et al. Prevalence of prolonged grief disorder in adult bereavement: a systematic review and meta-analysis. 

7. Prigerson HG, Bierhals AJ, Kasl SV, et al. Traumatic grief as a risk factor for mental and physical morbidity. 

8. Shear MK. Clinical practice. Complicated grief. 

Diagnostic and Statistical Manual of Mental Disorders

, 5th ed. American Psychiatric Association Publishing; 2013.

10. International statistical classification of diseases and related health problems (11th ed.) World Health Organization. 2019. Accessed August 18, 2021. 

11. Meert KL, Shear K, Newth CJ, et al. Follow-up study of complicated grief among parents eighteen months after a child's death in the pediatric intensive care unit. 

12. Kristensen P, Weisæth L, Heir T. Bereavement and mental health after sudden and violent losses: a review. 

13. Tal I, Mauro C, Reynolds CF 3rd, et al. Complicated grief after suicide bereavement and other causes of death. 

14. Zisook S, Reynolds CF 3rd. Complicated grief. 

15. Shear K, Frank E, Houck PR, Reynolds CF 3rd. Treatment of complicated grief: a randomized controlled trial. 

16. Shear MK, Wang Y, Skritskaya N, et al. Treatment of complicated grief in elderly persons: a randomized clinical trial. 

17. Iglewicz A, Shear MK, Reynolds CF 3rd, et al. Complicated grief therapy for clinicians: an evidence-based protocol for mental health practice. 

18. Clayton P, Desmarais L, Winokur G. A study of normal bereavement. 

19. Clayton PJ, Halikes JA, Maurice WL. The bereavement of the widowed. 

20. Clayton PJ, Darvish HS. Course of depressive symptoms following the stress of bereavement. 

, 3rd ed. American Psychiatric Association Publishing; 1980.

22. Zisook S, Corruble E, Duan N, et al. The bereavement exclusion and DSM-5. 

23. Iglewicz A, Seay K, Zetumer SD, Zisook S. The removal of the bereavement exclusion in the DSM-5: exploring the evidence. 

24. Zisook S, DeVaul RA. Grief, unresolved grief, and depression. 

25. Zisook S, Mohamad S, Johnson G, et al. Clinical implications of co-occurring prolonged grief disorder in patients with treatment-resistant major depressive disorder. 

26. Stroebe M, Schut H. Bereavement in times of COVID-19: a review and theoretical framework. 

27. Kokou-Kpolou CK, Fernández-Alcántara M, Cénat JM. Prolonged grief related to COVID-19 deaths: do we have to fear a steep rise in traumatic and disenfranchised griefs? 

Articles

How can clinicians distinguish between ordinary grief, depression, and prolonged grief disorder? 

Bereavement and Depression

We thank Dr Allen Frances for his thoughtful exploration of some common ground with our position on the bereavement exclusion (BE).

 Clearly, we all share the goals of respecting-not “medicalizing”-ordinary grief; as well as recognizing and treating clinically significant depression. We differ with Dr Frances in how to achieve these goals,

 while remaining faithful to the best available scientific data.

 In this piece, we try to clarify what is actually being proposed for DSM-5; how we differ or agree with Dr Frances’s most recent  proposals; and how arguments against eliminating the BE from DSM-V are ill-founded.

First, we need to highlight some myths and misunderstandings as regards elimination of the BE from DSM-5. No one who favors this change wants to imply that 

should be “over” within 2 weeks, 2 months, or even longer, after the death of a loved one. Rather, we argue that grief and major depression are 

, although there is some symptomatic overlap-a point we will explicate shortly. Moreover, many bereaved individuals grieve intensely for protracted periods, if not for a life time, whether or not they also meet criteria for a major depression episode (MDE). Furthermore, ordinary grief does not become pathological or mysteriously transformed into major depression after 2 months, 6 months, or 

number of months.  Rather, “normal” grief may last, in its various forms, for months to years .

 These points are not adequately explained in the DSM-IV, and need to be clarified in DSM-5.

At the same time, it is critical to note that for some vulnerable individuals, the death of a loved one may precipitate a MDE, and that in no sense is the person “immunized” against clinically meaningful depression by the recent loss-nor should our diagnostic classification imply otherwise. Moreover, when MDE develops in the context of bereavement, grief may be even more severe and protracted than otherwise. (Technically, “MDE” is not a formal DSM diagnosis, and the term major depressive 

 [MDD] should be used; however, to remain consistent with Dr Frances’s terminology, we will retain the term “MDE.”)

Now to some specific statements in Dr Frances’s piece that require comment:

“We [Zisook, Frances, and Pies] agree that the problem is the fuzzy boundary between normal grief and Major Depressive Episode (MDE).” 

Actually, we don’t quite agree with that formulation. To view the problem merely as one of “fuzzy boundaries” is to misapprehend the qualitative and categorical differences between ordinary grief and MDD, notwithstanding their symptomatic overlap (sadness, tearfulness, disturbed sleep, etc). Ordinary grief is not an “illness” at all, but a universal, adaptive 

If pressed to identify the “problem” with the present diagnostic system, we would point to its predilection for 

nullifying or undermining the diagnosis of MDD

, even when all symptom and duration criteria are met, solely on the basis of bereavement within the past 2 months.

“…severe depressive symptoms during bereavement are already meant to be diagnosed as MDE using the current guidelines in DSM-IV-TR. . .  If the grief symptoms are severe

DSM-IV-TR insists that MDE be diagnosed.” 

Dr Frances here argues that there is no need to eliminate the BE, because the current DSM framework already guards against missing MDE when it is “severe.” As we interpret the DSM-IV, this characterization is only partly correct. Within the current DSM framework, a clinician is justified in over-riding the BE 

only if certain “conditional” features of the depression are present

, such as severe psychomotor retardation, marked functional impairment, psychosis, and suicidality. However, there are many ways in which a bereaved person’s depression may be “severe” but not conform to DSM's over-ride criteria. Thus, a recently (less than 2 months) bereaved patient meeting symptom and duration criteria for MDE may have 

profound loss of pleasure, markedly decreased appetite, severely impaired concentration, and severe sleep disturbance

, and may score very high on the Hamilton or Beck Depression Inventory scales. All other things being equal, this patient would probably

receive a diagnosis of MDE using current DSM-IV-TR guidelines governing the bereavement exclusion

“…the test case is someone who has lost a spouse or child and has just two weeks of sadness and loss of interest, appetite, sleep, and energy. Such a person would have to be diagnosed with MDE if we were to follow the DSM 5 suggestion to simply remove the Bereavement exclusion.” 

We respectfully disagree. By DSM-IV’s-and almost certainly, DSM-5’s-rules, one can’t receive a diagnosis of MDE unless there is “… clinically significant distress or impairment in social, occupational, or other important areas of functioning.” So, in the “test case” Dr Frances describes, there would be no requirement-indeed, 

-for diagnosing MDE, absent “clinically significant distress or impairment” (admittedly, a judgment call). In the absence of such distress or impairment, we believe the clinician would be justified in simply using the current “V code” of bereavement. 

 In effect, we don’t need the bereavement exclusion to avert a diagnosis of MDD, so long as there is no finding of clinically significant distress or impairment. 

clinically significant distress and impairment accompanying the symptoms in Dr Frances’s test case, we would not want to preclude diagnosing an incipient bout of MDE-though, as Dr Frances would agree, the 2-week minimum duration (likely to be retained in DSM-5) may be too short a period to diagnose anything with confidence. In ambiguous cases of bereavement with depression, in which the “clinically significant distress or impairment” criterion is questionable, the clinician could diagnose 

Adjustment Disorder with depressed features

automatically compel clinicians to diagnose MDE in very recently bereaved individuals who meet mild symptomatic criteria for MDE, as in Dr Frances’s “test case.”

“. . . There is no research suggesting that the distinction between normal grief and mild MDE can be reliably and validly made so early after the loss of a loved one [ie, within 2 weeks].” 

Here we both agree and disagree with Dr Frances. The main problem with the 2-week minimum duration is not that it impairs our ability to distinguish ordinary grief per se from major depression. Rather, the 2-week minimum exacerbates the inherent difficulties of distinguishing mild MDE of short duration from any kind of non-pathological sadness, 

A 2-week period is also too short, in our view, to gauge adequately the “trajectory” of the patient’s symptoms; eg, whether they are waxing or waning. In our table, we suggest using additional data, such as personal and familial history of MDE, as well as phenomenological data, to make these difficult diagnostic calls.  Nonetheless, our position is generally in agreement with that of Dr Frances, when he writes that “…there is no need to medicate this griever having mild and completely expectable symptoms for so short a period [2 weeks or fewer]. We would both instead recommend a combination of commiseration, empathy, support, and watchful waiting…”.  However, if the depressive symptoms persist or intensify, more active treatment strategies become paramount.

“The diagnosis of MDE may be inappropriate if the individual's culture calls for a more profound expression of grief.” 

We agree that clinicians should remain aware of and sensitive to specific, culturally-based mourning rituals, such as “sitting shivah” (7-day mourning period) in the Jewish faith, or the 3-day funeral characteristic of Hmong culture.

However, we are not aware of any clinical studies showing that the standard DSM-IV criteria for MDE-including, it must be repeated, that of 

or incapacity-- are invalidated as a consequence of such cultural variations in grief and mourning. Indeed, since we believe that grief is a distinct construct from MDE, we would not expect any substantial confusion to arise in this regard, even when the person’s expression of grief is “profound” and intense.

“…to remove the Bereavement exclusion for MDE would disastrously open the floodgates to the misdiagnosis and overtreatment of normal grief  (especially by hurried primary care physicians who do much of the prescribing)… We can assume that drug advertising to patients and marketing to doctors will result in a flood of treatment that they would also question.” 

In contrast to the DSM-IV, the ICD-10 does not use or recognize a “bereavement exclusion” for  major depression. If Dr Frances is correct, we should be able to detect a signal of the “floodgates” opening in Europe and other parts of the world where the ICD-10 criteria for major depression are widely used. Yet we are not aware of data showing that the ICD-10 system leads to a vast increase in the prevalence of MDE, or to inappropriate treatment of depression.  On the contrary, European studies generally find similar depression prevalence rates when ICD-10 and DSM-IV criteria are compared.

Moreover, the actual percentage of patients presenting with bereavement-related depression is likely to be small, in comparison with the total number of depressed patients; eg, Corruble et al

found that, of their total sample of patients with depression, 8.5% would have been “excluded” by virtue of bereavement, using the DSM-IV BE exclusion rules. This is not a trivial number, but it does not suggest to us that the “floodgates” would open in the US if the BE were dropped from DSM-5. Furthermore, we would expect only a small fraction of this percentage to present to a clinician 

, based on our clinical experience; hence, Dr Frances’s “test case” would probably be an exceedingly rare occurrence in the psychiatrist’s office. Rather, depressed and grieving patients presenting only 2 weeks after bereavement would likely be limited to a few hospitalized patients who had developed a psychotic depression or who had made a frank suicide attempt-in which cases the BE would not apply anyway. With respect to “over-treatment of normal grief” by harried PCPs, we regard this hypothetical outcome as a matter best addressed through medical education and consultation with our PCP colleagues-not by retaining a diagnostic scheme that flies in the face of the best available data. More important: most studies of primary care have pointed to high rates of 

treatment of major depression-a problem we regard as far more serious than the hypothetical risk of PCPs “over-calling” grief as major depression. Indeed, in primary care settings, up to 50% of MDE cases go unrecognized, and treatment is often inadequate.

We would invite  Dr Frances to cite contrary studies showing that PCPs frequently over-diagnose “normal grief” as MDE, as we are unaware of such findings.

“It is an unproven and unlikely red herring that the DSM 5 change will save lives (or for that matter have any beneficial effect at all)…”

 We have never claimed that eliminating the BE from DSM-5 will “save lives.” What we have said is that

creates a completely unnecessary and avoidable risk; ie, that potentially serious MDE will be misperceived and misdiagnosed as “just normal grieving.” In principle, this could lead to potentially suicidal individuals being sent home with nothing more than a, “There, there-you just need time to grieve,” from the misguided clinician. What we believe is an “unproven and unlikely red herring” is Dr Frances’s “open floodgates” scenario. It will of course require empirical studies, after DSM-5 is operationalized, to determine the actual effects of eliminating the BE, if that is what the DSM-5 work group decides.

“There is no proven efficacy for medication treatment given after just 2 weeks of mild symptoms in grievers….” 

Of course, we agree, and we would never advocate antidepressant treatment for uncomplicated, “normal” grief of 

. Indeed, even for mild-to-moderate cases of MDE, we would usually opt for psychotherapy as the treatment of first choice. That said, we would point out that when grief is part of 

, there is preliminary evidence that antidepressants may be of benefit and do not interfere with the grieving process.

“Reasonable people can disagree about the precise duration requirement before grief can be considered mild depression… Pies/Zisook suggest 1 month. I am OK with the DSM-IV-TR 2 months…”

 We believe Dr Frances is conflating several different time frames and conditions. First, we must again note that grief does not somehow metamorphose into depression-mild or otherwise-

, nor are we advocating a “time limit” on ordinary grief. Grief is grief; depression is depression (Table). Our “1 month” proposal refers to the minimal duration we would like to see applied, in most cases, to the 

(we allow for shorter duration when melancholic, psychotic, or suicidal features are present). Further research and field trials will be needed to determine the most useful “cut-offs” for these types of depression. The “2 months” Dr Frances alludes to has nothing directly to do with when “grief can be considered mild depression”; rather, the 2 month criterion is simply the 

 ie, when MDD symptoms occur beyond 2 months after bereavement, DSM-IV implies that use of the BE (all other things being equal) is not warranted. We believe all these issues could be set aside if the DSM-5:
•Drops the BE
•Increases the minimal duration to 1 month, for most cases of first episode, nonpsychotic  MDE
•Clearly describes the phenomenology and symptom picture for ordinary grief and bereavement.

To conclude: We believe that the BE is simply unsupportable by the best available data, and that eliminating it from the DSM-5 will remove a confusing and potentially harmful distraction from the clinician’s deliberations. We do not anticipate that any “floodgates” will open by eliminating the BE, nor do we think our recently-bereaved patients who meet MDE criteria will feel disrespected by our honest and empathic judgment that they are also clinically depressed and merit our professional care. 

Major Depressive Episode (moderate to severe) with or without bereavement/ recent loss

Uncomplicated (“Normal”, “Productive”, “Adaptive”) Grief

Sadness, tearfulness, sleep disturbance, decreased socialization, decreased appetite

Usually, prolonged, persistent impairment in ability to carry out most activities of daily living (ADLs); pronounced, persistent social/vocational impairment; social relations often poorly maintained; pronounced psychomotor slowing or agitation; consistent early a.m. awakening, pronounced weight loss are common.   

Variable, but often able to carry out most ADLs after first 1-2 weeks of bereavement; often able to maintain most social/vocational role responsibilities and relations after first 1-2 weeks; no consistent or prolonged psychomotor impairment; initial insomnia more common than consistent early a.m. awakening; weight loss usually mild/ moderate.

 (contents & structure of  person’s experience, “world-view”) *

Mood depressed all day, nearly every day; depression is autonomous (not mitigated by positive stimuli); commonly: pronounced pathological guilt, self-loathing, markedly lower self-esteem, feels “worthless”; hopelessness, suicidal intentions or plans common; delusional beliefs may be present, often of nihilistic nature.

Person feels depression will never end; sense of bleak future, feeling “trapped”, imprisoned; thoughts constantly negative, self-focused; even with support, often feels “outcast”, alienated from others; inconsolable even with distraction, music, etc.  May feel like “sinner”, “condemned by God,” “rotting away” , “deserve to die”, etc. (psychotic MDE)

Sadness comes in “waves” most days but bereaved also has “good” days; waves of sadness brought on by thoughts/images of the deceased; bereaved not pathologically guilt-ridden (guilt confined to wishing they had “done more” for deceased or been more compassionate); self-esteem preserved, no self-loathing. Hopelessness uncommon; thoughts of death, suicidal ideas confined to reunion fantasies, not frank suicidal urges or plans; not delusional (but visual/auditory hallucinations of deceased are common).

 Bereaved usually believes life will someday get back to normal, he/she will again feel like “old self”;  positive thoughts & memories interspersed with painful recollections of deceased; with appropriate support, bereaved does not feel “outcast”, alienated; often able to make use of and appreciate love, support; often able to be consoled by family & friends, music, literature, etc; does not feel like “sinner”, “condemned”, deserving of death; no nihilistic delusions but may feel “like part of me is missing” or “I lost the best part of me.”

Past mood disorder history/psychiatric comorbidity

Often positive for previous bout of major depression; co-morbid psychiatric disorders (anxiety, OCD, etc) common

May or may not have any history of mood disorder or other psychiatric disorders

Often positive for depression in first-degree relatives

May or may not have family history of mood disorder

Melancholic cases frequently associated with abnormal HPA axis activity, elevated cortisol; PET studies often show abnormal frontal lobe activity (↑
or ↓)

Insufficient data but no consistent evidence to date of major biological disturbances in the absence of concurrent mood disorder

Moderate to severe cases show response to antidepressants > placebo; severe/melancholic,
psychotic depression highly responsive to ECT

Insufficient data, but no evidence that somatic treatment is needed; most episodes resolve with time and support. In cases with concurrent MDE, antidepressants do not appear to interfere with grief work

Responsive to CBT, IPT and other psychotherapies

Support groups and grief counseling may be useful in some cases, but no evidence that psychotherapy is required for resolution of ordinary grief

Good for acute episode, though up to 1/3 cases may be treatment-resistant; major depression sometimes chronic and usually recurrent.  

Excellent unless “complicated” by concurrent MDE or other psychiatric disorder or psychopathology.

 *There is considerable variability in both MDE and uncomplicated grief, and these differentiating features are intended only as general guidelines. While the majority of individuals with these conditions tend to show the differences indicated, exceptions are often seen in clinical practice, and the first few weeks after bereavement may be particularly intense and distressing, leading to diagnostic confusion. In 

 of MDD, if symptoms are mild and distress equivocal, we generally recommend waiting a month after symptom onset before making a firm diagnosis.  In 

in cases when the distress or impairment is obvious;  when the index depressive presentation is characterized by melancholic or psychotic features or suicidality; or when the presentation is  similar to that of a previous, well-documented major depressive episode, we do not feel that waiting even as long as 2 weeks is necessary for making a diagnosis of MDE or instituting treatment.   

1. Zisook S, Shear K. Grief and bereavement: what psychiatrists need to know. World Psychiatry. 2009;8(2):67-74.

2. Lee K. Rituals, Roles, And Responsibilities Included In A Hmong Funeral: A Guidebook For Teachers To Better Understand The Process Their Hmong Students Experience In A Time Of Family Loss. Doctoral dissertation. Available at: csuchico-dspace.calstate.edu/...4/.../11%2029%202009%20Kirk%20Lee.pdf. Accessed Sept. 24, 2010.

3. Ayuso-Mateos JL, Vazquez-Barquero JL. Depressive disorders in Europe: prevalence figures from the ODIN study. British J Psych. 2001;179:308-316.

4. Corruble E, Chouinard VA, Letierce A, et al. Is DSM-IV bereavement exclusion for major depressive episode relevant to severity and pattern of symptoms? A case-control, cross-sectional study. J Clin Psychiatry. 2009;70(8):1091-1097. Epub 2009 Jun 30.

5. Saver BG, Van-Nguyen V, Keppel G, et al: A qualitative study of depression in primary care: missed opportunities for diagnosis and education. J Am Board Family Med. 2007;20:28-35.

6. Zisook S, Shuchter SR, Pedrelli P, et al. Bupropion sustained release for bereavement: results of an open trial. Clin Psychiatry. 2001;62(4):227-230.

7. Hensley PL, Slonimski CK, Uhlenhuth EH, et al. Escitalopram: an open-label study of bereavement-related depression and grief. J Affect Disord. 2009;113(1-2):142-149. Epub 2008 Jul 2. 

Clearly, we all share the goals of respecting-not “medicalizing”-ordinary grief; as well as recognizing and treating clinically significant depression. We differ with Dr Frances in how to achieve these goals, while remaining faithful to the best available scientific data. 

Grief and Depression Redux: Response to Dr Frances’s “Compromise”

Disentangling Grief and Depression
By Allen Frances, MD

The recently posted draft of DSM5 makes a seemingly small suggestion that would profoundly affect how grief is handled by psychiatry. It would allow the diagnosis of Major Depression even if the person is grieving immediately after the loss of a loved one. Many people now considered to be experiencing a variation of normal grief would instead get a mental disorder label.

Undoubtedly, this would be helpful for some people who would receive much needed treatment earlier than would otherwise be the case. But for many others, an inaccurate and unnecessary psychiatric diagnosis could have many harmful effects. Medicalizing normal grief stigmatizes and reduces the normalcy and dignity of the pain, short-circuits the expected existential processing of the loss, reduces reliance on the many well-established cultural rituals for consoling grief, and would subject many people to unnecessary and potentially harmful medication treatment.

Grief is an inescapable part of the mammalian experience and a necessary correlate of our ability to attach so strongly to other people. Although grief is universal, there is no one right way to grieve. Different cultures prescribe a wide variety of different behavioral and emotional reactions and rituals. Psychiatry needs to tread lightly and have compelling reasons before encroaching with its own rituals on such time-honored and usually effective practices.

Within a given culture, normal individuals also vary enormously in the content, symptoms, duration, and impairment of their grief and in their ability to draw consolation and sustenance from others. There is no bright line separating those who are experiencing loss in their own necessary and particular way from those who will stay stuck in a depression unless they receive specialized psychiatric help.

The numbers on each side of the normal/mental disorder divide are probably very lopsided. Ever since the origin of our species, every human has had frequent occasions to grieve. Almost all of us come to terms with the loss and the altered conditions of a new life without the benefits of psychiatry-and do just fine on our own. The change in DSM5 would attempt to identify the very small percentage of people who have a complicated grief that goes beyond the average expectable in severity, symptom pattern, and duration -those who would not remit as part of the natural evolution of their grief. But when you use a big shovel to capture a small needle in the haystack, what you mostly get is hay. Any change in the way DSM5 defines grief may gather a very large proportion of false positives who would do better avoiding psychiatric help.

The rationale given by DSM5 for its radical proposal is brief, cryptic, and fails to provide anything like a risk-benefit analysis of potential effects. DSM5 states that there is no evidence that the stress of losing a loved one is different from other stressors and thus no justification to withhold the diagnosis of major depression after a loss. This rationale places the burden of proof in the wrong direction. DSM5 should make so consequential a change only after a careful and considered evaluation proves with compelling evidence that it will do more good than harm.

Such evidence is simply not available. The research in this area is interesting but in very early development and we don’t know many essential things. We have no idea how any proposed criteria set would work in the general population. What percentage of grieving individuals would be given the diagnosis (especially once drug companies raise awareness of it)? Among these individuals, we don’t know what percentage truly need psychiatric help and what percentage would do better without it.

In a recent commentary, Drs Ron Pies and Sidney Zisook

 have gone far beyond the meager DSM5 rationale to present the strongest possible case for allowing the diagnosis of Major Depression in grief situations. They cite several lines of argument:

1. There is a clinical need-some individuals have severe, complicated grief that looks just like severe Major Depression and that does not get better spontaneously. The longer that diagnosis and treatment are delayed, the greater their suffering, impairment, and risks (eg, job loss, injured relationships, lowered treatment response, suicide).

2. The loss of a loved one is not essentially different from the many other serious stressors that abound in life.

3. It is impossible to predict the future misuse of the DSM5 system, so we should make decisions based only on the best possible science.

4. The criteria for complicated grief could be tightened to reduce false positives. (They suggest 2 useful ways described below and I add 2 others).

5. Education can solve the problem of false-positive diagnosis and the risk of providing medicine in milder cases when time, support, and/or psychotherapy would be more indicated.

The excellent proposal made by Pies and Zisook to reduce false positives could be strengthened even further if 2 additional exclusions were added (see 1 and 2 below). The entire package differentiating grief from depression would require:

2. A particularly severe presentation that includes some combination of unreasonable guilt, worthlessness, hopelessness, self-loathing, anhedonia, a focus on negative memories of the departed, alienation from others, and inability to be consoled.

3. To recognize the different cultural expressions, the diagnosis of depression would not be made if the person’s grief is within cultural norms.

4. An exclusion could be added that would take into account the person’s own past experience of grief and its previous outcomes. If the individual previously had severe grief symptoms but recovered spontaneously (without going on to a major depression), this would suggest they are now grieving their own way and do not require diagnosis or treatment.

DSM5 has made many poorly thought-through suggestions that can be fairly easily dismissed. Although I continue to disagree with the Pies/Zisook proposal, it is reasonable and deserves serious consideration. Here are the opposing points:

• Re clinical need: In appropriate cases displaying clinically significant impairment, distress, or risk, the diagnosis Depression Not Otherwise Specified covers their false-negative problem.

• I believe there is a difference between losing a loved one and most other life stressors.

This explains why grief is the universal target of communal healing rituals. It would be unfortunate for psychiatry to prematurely roam into problems usually better handled by family and other cultural institutions. Cultural biases would be very hard to surmount in making this diagnosis.

My disagreement with Pies and Zisook is strongest on this point. All decisions for DSM5 should follow the injunction-“First Do No Harm.” Although it is impossible to predict precisely how any DSM5 change will eventually play out once the manual is in general use, that doesn’t reduce DSM’s responsibility for the problems that occur-even if they are unintended. All potential risks have to be thought through and factored into a thorough risk-benefit analysis. The argument that we should just go to where the science takes us ignores the fact that the science is (as they point out) not definitive, is subject to different interpretations, and is not readily generalizable from research to real-world settings. Once the genie is out of the bottle and DSM5 makes it easy to diagnose depression in grief situations, this could easily become an industry-propelled fad diagnosis.

• The tightened criteria would help reduce, but certainly not eliminate, the grave potential harm caused by the massive misidentification of false positives. False positives and excessive treatment are not a problem for skilled and cautious clinicians (like Pies and Zisook), but in the real world, most of the prescriptions will be written by primary care physicians who have 6 minutes with each patient, don’t know the fine points of the criteria sets, and want the fastest solution. The false-positive problem is too unknown and potentially far too large to ignore. At a minimum, there would need to be field trials to determine prevalence, reliability, false-positive, and false-negative rates. I doubt that DSM5 has the time, money, and skill to pull this off.

• It would be naive and unwise to rest our hopes that any educational program would reduce overdiagnosis and the overprescription of medication in grief situations. To the contrary, most of the education would go the other way. The drug companies devote enormous resources to “educating” physicians to be quick on the draw in prescribing medication.

I respect the arguments made by Pies and Zisook and believe they work well when applied by experts like themselves. My worry is the misuse of even reasonable ideas in the real-world situations where most diagnosis and treatment is done. Loose diagnostic and treating habits could lead to the widespread medicalization of grief well beyond what Pies and Zisook would themselves recommend.

• The first is to keep things as they are and not to diagnose major depressive disorder in the first 2 months after the loss of a loved one.

• The second is for DSM5 to allow for the diagnosis of complicated grief but with a criteria threshold set high and including all 4 protections against false positives outlined above. As recommended by Pies and Zisook, there should also be a physician and public education campaign normalizing normal grief and sharply delimiting the small group of grievers who need psychiatric help.

Weighing the pluses and minuses, my call is to keep things as they are and not to risk an “epidemic” of psychiatric grief.

The recently posted draft of DSM5 makes a seemingly small suggestion that would profoundly affect how grief is handled by psychiatry.

Sidney Zisook, MD

Articles

Bereavement and Depression

Grief and Depression Redux: Response to Dr Frances’s “Compromise”

DSM5 and the Medicalization of Grief: Two Perspectives

DSM5 Criteria Won’t “Medicalize” Grief, if Clinicians Understand Grief

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