Sidney Zisook, MD

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. 

Articles

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.

 Pies R, Zisook S. DSM5 criteria won’t “medicalize” grief, if clinicians understand grief. 

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

Disentangling Grief and Depression: Rejoinder to Dr Frances
Ronald Pies, MD And Sidney Zisook, MD

We appreciate Dr Frances’ thoughtful rejoinder to our essay, and we recognize that his disagreements with us are motivated by goals we all share-ensuring the well-being of those who seek our help and reducing the suffering and incapacity of seriously depressed patients.

The last thing we would want to do is pathologize “normal grief”-just as we know that Dr Frances would not want to “normalize” bona fide Major Depression. We all agree that finding the specific line demarcating “normal” depressive feelings and thoughts (depression with a small “d”) from clinically meaningful Depression (with a big “D”) is often challenging, even for the most astute and experienced clinicians. We also agree that the ideal research studies defining the full spectrum of normal depression through pathological Depression and demarcating the boundaries of these conditions have not been done. Thus, the best we can do is to be guided by the best available data.

However, we respectfully disagree with Dr Frances on what the “best available evidence” tells us. We stand by our previous review

 of the most pertinent recent data, which informs us that continuing the bereavement exclusion (BE) for the diagnosis of major depression does more harm than good. The BE ignores much of this recent evidence,

 and we agree with the DSM committee’s pithy but astute rationale for discontinuing the BE-that there is no credible evidence that bereavement-related depression is different (in severity, course, morbidity, comorbidity, consequences, or treatment response) from other, non–bereavement-related instances of major depressive episodes.

Notably, the International Classification of Diseases (ICD-10) also omits the BE. While rates of clinically serious depression may be somewhat higher when ICD-10 (vs DSM-IV) criteria are used, we are not aware of any evidence demonstrating an “epidemic of psychiatric grief” resulting from the use of ICD depression criteria.

We agree with Dr Frances that the honored maxim “First, do no harm” should be one important guiding principle behind the DSM5’s categories. However, we may differ with Dr Frances on how “harm” ought to be defined and assessed in this context. We believe that the harm that may ensue if ordinary grief is “overdiagnosed” as major depression pales in comparison with the harm that may follow a missed diagnosis of major depression.

If a patient with ordinary grief or bereavement is (mistakenly) given a diagnosis of major depressive disorder (MDD), the attendant “risks” are mainly those of entering the mental health system and receiving treatment-whether psychotherapy or medication. Both “talk therapy” and medication may entail risk, and we are well aware of the unpleasant and sometimes harmful side effects antidepressants may produce in a minority of patients. However, given that completed suicide is the outcome in roughly 4% of patients with MDD-averaged for outpatients (2%) and inpatients (6%)6-we believe that far greater harm will befall our patients if the BE is retained. This would encourage practitioners to “extrude” from the category of MDD many patients whose symptoms of major depression occur within 2 months of a recent loss-for which, we believe, there is insufficient scientific basis. Some evidence even suggests that use of the BE may “backfire”-identifying more severely depressed individuals than controls with major depression but without bereavement.

 Zisook S, Kendler KS. Is bereavement-related depression different than non-bereavement-related depression? 

 Zisook S, Shear K, Kendler KS. Validity of the bereavement exclusion criterion for the diagnosis of major depressive episode. 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219913

 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. 

 Guerra M, Ferri CP, Sosa AL, et al. Late-life depression in Peru, Mexico and Venezuela: the 10/66 population-based study. 

 US Dept of Health and Human Services. Lifetime risk for suicide in depression. 

http://mentalhealth.samhsa.gov/suicideprevention/risks.asp

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

 Pies R. The anatomy of sorrow: a spiritual, phenomenological, and neurological perspective. 

 Ani C, Bazargan M, Hindman D, et al. Depression symptomatology and diagnosis: discordance between patients and physicians in primary care settings. 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2254627/?tool=pubmed

DSM5 and the Medicalization of Grief: Two Perspectives

“The exclusion of symptoms judged better accounted for by Bereavement is removed because evidence does not support separation [or] loss of loved one from other stressors.”

With this simple rationale, the framers of DSM5 would, according to 

,  “…reverse 30 years of diagnostic practice and allow the diagnosis of Major Depression to be made for individuals whose grief reaction symptomatically resembles a Major Depressive episode.”

We respect Dr Frances’s numerous attempts to improve the DSM5 process and acknowledge that he has raised important questions about several proposed DSM5 diagnoses.

 However, we support the proposal to eliminate the bereavement exclusion from the criteria for Major Depressive Episode (MDE) and disagree that this amounts to “medicalizing normal grief.”

Indeed, we believe it begs the question-that is, assumes as true precisely what is in dispute-to suggest that someone who meets full symptom and duration criteria for MDE after a major loss merely “resembles” someone with a MDE. Nor do we believe that “grief reaction” is necessarily the right term for someone who meets full symptom and duration criteria for MDE, but who happens to present within two months of a major loss, including but not limited to the death of a loved one. 

And, while we take Dr Frances’s point that “…grief would become an extremely inviting target for the drug companies”

, we believe that DSM5 criteria sets should be based on the best available science, not on predications regarding the behavior of pharmaceutical companies. Furthermore, by eliminating the bereavement exclusion, the DSM5 would bring its criteria for MDE in line with those of the International Classification of Disease, 10th edition (ICD-10). In the ICD-10, if Mr Jones meets criteria for a depressive episode-- notwithstanding the recent death of his wife-- he gets the diagnosis of depressive episode, subtyped as mild, moderate, or severe.

We fully expect that this paradigm will continue in the ICD-11, now anticipated in 2014.  Harmonizing the DSM and ICD criteria is consistent with a goal advocated by Dr Frances himself.

So what, in our view, does the best available science show? While acknowledging that definitive studies have yet to be done, we believe the best studies to date 

 lead to the following conclusions:
1.      There are no convincing data that show depression in the context of loss to be fundamentally different than any other kind of depression, when full DSM symptom and duration MDD criteria are met.
2.    In contrast, there is evidence demonstrating that Bereavement-Related Depression (BRD) is similar to other instances of  depression occurring in the context of other major losses (job loss, divorce, etc.) in terms of risk factors, severity, associated features, patterns of co-morbidity, biology, course and treatment response.
3.      The current (DSM-IV) differentiating features for bereavement are not predictive of lower depression severity or risk.
4.   There are no convincing data showing that the bereavement exclusion for the diagnosis of major depression protects against “pathologizing” normal grief, or against over-diagnosing major depression.
5.     In contrast, it is not unlikely that the bereavement exclusion may lead, paradoxically, to keeping some severely depressed individuals who happen to be bereaved, or whose depressive episode was precipitated by death of a love one, from receiving much- needed treatment.
 
As we stated previously, we believe “…that continuing the bereavement exclusion in DSM5 would be a serious error. It would encourage bereaved individuals, their families, and health care providers to ignore signs and symptoms of a potentially debilitating, life-threatening, yet treatable disorder. Extending this exclusion to still other loss events could create a public health disaster.”

For example, in ordinary or “productive” grief

 and bereavement, the individual typically maintains her emotional connection with others; believes that the grief will end some day; maintains her self-esteem; and experiences positive feelings and memories along with painful ones. Guilt, if present, is focused on “letting down” the deceased person, rather than on being “worthless” or useless. In ordinary grief, loss of pleasure is related to longing for the deceased loved one, as opposed to the pervasive anhedonia often seen in severe depressions; and suicidal feelings are more related to longing for 

 with the deceased than to thoughts of not deserving to live.  Moreover, as Dr Kay R. Jamison has noted, in ordinary grief, an individual is capable of being “consoled” by friends, family, music, literature, etc.

In contrast to all this, in severe depression-particularly in the melancholic subtype-the individual tends to be extremely “self-focused”; feels outcast or alienated from friends and loved ones; has the sense that the depression will “never end”; experiences profound self-loathing and guilt; experiences few if any positive feelings or memories; and is often “inconsolable.” 

We acknowledge that careful empirical investigation is required to confirm these largely observational findings; but we believe that the DSM5 text should include such phenomenological descriptors, even if the official criteria sets do not. In the mean time, we urge further investigation into both the biology and phenomenology of uncomplicated grief, complicated (pathological) grief, and MDD.

In conclusion, we do not believe that elimination of the bereavement exclusion by itself will lead to the “medicalization” of grief; rather, we believe it will encourage those with potentially serious depressive illness, after recent loss, to seek help. Nor do we believe that elimination of the bereavement exclusion by itself will lead to over-medication, so long as clinicians are trained to apply DSM-5 criteria for MDE; to avoid premature prescription of antidepressants (eg, within the first week of depression); and to consider psychotherapy as the first-line treatment for short-lived, mild-to-moderate depression. To be sure, all this will require stepped-up training of both psychiatric and (especially) primary care physicians. 

Finally, we believe  it is time for the DSM to look more carefully at phenomenology-the contents of the patient’s felt experience-rather than relying almost entirely on behavioral and symptomatic check-lists.

 1.http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=427#

2.Frances A:   Opening Pandora’s Box: The 19 Worst Suggestions For DSM5. http://www.psychiatrictimes.com/home/content/article/10168/1522341?pageNumber=2&verify=0

3.Frances A: A Warning Sign on the Road to DSM-V http://www.searchmedica.com/resource.html?rurl=http%3A%2F%2Fwww.psychiatrictimes.com%

2Fdsm%2Fcontent%2Farticle%2F10168%2F1425378%3FpageNumber%3D2&q=Frances+A.+A+Warning+Sign+on+the+Road+to+DSM-V%3A+Beware+of+Its+Unintended+Consequences.&c=ps&ss=psychTimesLink&p=Convera&fr=true&ds=0&srid=2

4.Zisook S, Kendler KS: Is bereavement-related depression different than non-bereavement-related depression.  Psychological Medicine: 1-31, 2007

5. Zisook S, Shear K, Kendler K. Validity of the bereavement exclusion criterion for the diagnosis of major depressive episode. World Psychiatry. 2007 June; 6(2): 102â107. Accessed at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219913/

6. 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 Aug;70(8):1091-7. 

7. Zisook S, Pies R. Letter, Psychiatric Times (response to Wakefield and Horwitz)http://www.psychiatrictimes.com/display/article/10168/1413394

8. Pies R. The anatomy of sorrow: a spiritual, phenomenological, and neurological perspective. Philos Ethics Humanit Med. 2008; 3: 17. Accessed at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442112/

9. Ghaemi SN. Feeling and time: the phenomenology of mood disorders, depressive realism, and existential psychotherapy. Schizophr Bull. 2007;33:122â30.  10. Zisook S, Shear K. Grief and bereavement: what psychiatrists need to know.  World Psychiatry. 2009 June; 8(2): 67â74. Accessed at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2691160/

11.Jamison KR. Nothing Was the Same. New York, Knopf, 2009. 

“The exclusion of symptoms judged better accounted for by Bereavement is removed because evidence does not support separation [or] loss of loved one from other stressors.”1

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

“It is not enough to add years to one’s life . . . one must also add life to those years.” -John F. Kennedy

We are growing older. In ancient Greece, the expected life span was 20 years. In Medieval Europe, it went up to 30 years. In 1900, people reasonably could expect to live to the ripe old age of 47 years, and 39% of those born at that time survived to age 65 years in the United States. Currently, the average life span in the United States is 78 years, and 86% of those born will survive to age 65 years. The very old-people older than 85 years-are the fastest-growing population group in the country, and there are 120,000 Americans over the age of 100 years. And the trend continues.

According to the US Census Bureau, by 2020, 58% of all those born will survive to age 85 years, and by 2050, almost a quarter of the US population will be older than 65 years. Nor is the graying of our population just a local phenomenon. In 2006, for example, Japan became the first country to have 20% of the population reach age 65 years-plus. As our population grows older, physicians may anticipate seeing a greater proportion of their friends, relatives, and patients with late-life mental illness, bereavement, and perhaps even vulnerability to elder abuse. Like it or not, specialty-trained in geriatric psychiatry or not, most psychiatrists of adults will be “geriatric psychiatrists.”

Mental illnesses, at any age, are common and often long-term, and people with these chronic conditions now live longer. To compound the problem, the percentage of the population with mental illness is expected to increase as more illnesses have progressed to earlier ages of onset, resulting in a higher incidence of mental illness than in previous generations.

As physical problems increase, as family and friends die or drift away, as finances decline or other age-related stresses appear, mental health problems become more overwhelming. In addition, as people live longer, they have more opportunities for new mental disorders to develop that are sometimes linked to chronic physical conditions such as diabetes or hypertension or other brain disorders such as Alzheimer or Parkinson disease. Indeed, late-onset mental disorders account for about 25% of the cases in older adults. In addition, in a large percentage of people with degenerative or other types of dementia disorders, new-onset psychosis, agitation, anxiety, or depression also develop; this can be the cause of behavioral problems that lead to institutionalization when caregivers can no longer manage the patient at home.

Older persons with mental illness may be the most heavily burdened age group of any population, with the dual millstones of being old and mentally ill. Thus, it is no surprise that the suicide rate among the elderly is higher than in any other age group.

With this as background, the collection of articles found in this Special Report could not be more timely. They represent a broad array of many of the most common and clinically vexing mental health challenges facing older persons. Each contribution provides a scholarly review of what is known and offers clinical pearls pertinent to any clinician treating the elderly.

Three of the most common disorders throughout the adult life cycle are mood, anxiety, and substance use disorders. While most clinicians recognize how prevalent and disabling late-life depression can be, fewer are familiar with the particular manifestations and treatment requirements of late-life bipolar, general anxiety, or substance use disorders.

Anxiety disorders tend to be more prominent in the lives of older adults than many clinicians realize. Little has been written about the treatment of late-life anxiety disorders, and 
clinicians often are at a loss where to begin. Calleo and Stanley address this problem and provide some answers about how to manage anxiety in older adults.

Substance use disorders, including the misuse and abuse of prescribed medications, are public health crises in the elderly that are often overlooked and thus untreated or inadequately treated. Trevisan reviews the implications of the aging of the baby boomer population and the rise in the prevalence of substance abuse among older persons.

Lavretsky provides an up-to-date primer on the unique clinical characteristics, epidemiology, differential diagnosis, etiology, and treatment of a full spectrum of mood disorders in late life.

Next, Hensley and Clayton discuss a universal and ubiquitous problem for the elderly-bereavement. One of the most painful of all the common experiences of growing old is the fact of death, frequently that of our closest and often life-long friends and relatives.

When is the depression following such a loss “just grief” and when is it a clinically significant depres-sion begging for treatment? Few areas in clinical medicine are less well understood.

The article by Kyomen and Whitfield provides a comprehensive and pragmatic review of agitation in the elderly. The causes of agitation in this vulnerable population are myriad and associated with a number of physical and mental conditions.

This outstanding collection of articles thus serves as an update and refresher course that covers key topics in geriatric psychiatry. It is an honor to present them here, and I hope you get as much out of reading them as I did.

Dr Zisook reports that he has received research support from PAMLAB, ASPECT, and NIMH; he has received honoraria from GlaxoSmithKline, Wyeth, Forest, and AstraZeneca.

Current Knowledge and Future Direction

Everyone would probably agree that the practice of clinical psychiatry has changed profoundly over the second half of the past century. One of the most remarkable changes has been the rapid development and expansion of clinical psychopharmacology, which has become, like it or not, a dominant part of the clinical practice of most psychiatrists. Available treatments for mental disorders changed and our armamentarium broadened. We have numerous medications for psychiatric disorders. We even use medications for disorders traditionally considered only amenable to and suitable for psychotherapy.

Clinical psychopharmacology, after its growing pains, has become a full-fledged, complicated discipline. New medications appear all the time that have various, at times complicated and serious, adverse-effect profiles. Drug-drug interactions have become an important issue. Clinical studies comparing psychotropic medications and reports on their benefits or dangers appear each month in psychiatric journals. The evidence base of clinical psychopharmacology keeps growing at an amazing rate. Pharmacoeconomics is already changing our practice, and new pharmacogenetic technologies seem to be on the verge of changing it even more.




The knowledge base of clinical psychopharmacology is clearly growing and becoming increasingly complex. It is obvious that because of information overload, any one person's expertise in all aspects of clinical psychopharmacology has to be decreasing. Nevertheless, clinical psychiatrists need to be educated and skilled in all aspects of clinical psychopharmacology. Thus, because of the growing complexity of psychopharmacology there is a need for creating some kind of "collective expertise and wisdom" by the experts in the field, which needs to be taught to physicians by using innovative teaching methods.

As Glick and colleagues noted, "psychopharmacology was taught using an apprenticeship model, with trainees expected to learn about medications by shadowing their mentors, reading in libraries, and applying that knowledge to the cases they saw."

 While using the apprenticeship model in clinical psychopharmacology may be practical and useful, this educational practice cannot embrace all the intricacies and complexities of the field. Furthermore, this model raises the important issue of whether the mentors themselves are keeping up with the developments in the field and, if so, how they do it. The "amount of material needing to be taught has expanded, [while] the resources available to do the job have contracted."



The 2 traditional sources of information for clinicians and experts, journals and psychopharmacology textbooks, have their own strengths and weaknesses. The number of journal articles and the complexity of their interpretation are increasing. Publication bias may be difficult to untangle at times. Textbooks usually bring a huge, comprehensive volume of information that may be somewhat difficult to digest, and they may be somewhat outdated because of the publication delay of books. Thus, there is a great need for a summary of information that:

• Is generated by experts.
• Is up-to-date.
• Is comprehensive yet relatively easy to understand.
• Is easy to use for teaching purposes by those who may not be experts in every aspect of the field. 
• Is easy to update, revise, and adapt to local needs ("portable").
• Uses new technologies.
• Is unbiased and not influenced by the pharmaceutical industry.



Everyone would probably agree that the practice of clinical psychiatry has changed profoundly over the second half of the past century. One of the most remarkable changes has been the rapid development and expansion of clinical psychopharmacology, which has become, like it or not, a dominant part of the clinical practice of most psychiatrists. Available treatments for mental disorders changed  and our armamentarium broadened. We have numerous medications for psychiatric disorders. We even use medications for disorders traditionally considered only amenable to and suitable for psychotherapy.

Sidney Zisook, MD

Articles

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

Current Knowledge and Future Direction

A New Tool for Teaching Psychopharmacology