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Prolonged grief disorder is a stress syndrome after the death of a loved one, in which the person feels persistent, intense grief for longer than expected by social, cultural, or religious practices. About 3 to 10 percent of people develop prolonged grief disorder after the natural death of a loved one, but the incidence is higher when a child or partner dies, or when a loved one dies unexpectedly. Depression, anxiety and post-traumatic stress disorder should be examined in clinical evaluation. Evidence-based psychotherapy for grief is the primary treatment. The goal is to help patients accept that their loved ones are gone forever, to lead meaningful and fulfilling lives without the deceased, and to gradually dissolve their memories of the deceased

A case
A 55-year-old widowed woman visited her physician 18 months after her husband’s sudden cardiac death. In the time since her husband’s death, her grief has not eased at all. She couldn’t stop thinking about her husband and couldn’t believe he was gone. Even when she recently celebrated her daughter’s college graduation, her loneliness and longing for her husband did not go away. She stopped socializing with other couples because it made her very sad to remember that her husband was no longer around. She cried herself to sleep every night, thinking over and over how she should have foreseen his death, and how she wished she had died. She had a history of diabetes and two bouts of major depression. Further assessment revealed a slight increase in blood sugar levels and a 4.5kg (10lb) weight gain. How should the patient’s grief be assessed and treated?

Clinical problem
Clinicians who treat grieving patients have an opportunity to help, but often fail to take it. Some of these patients suffer from prolonged grief disorder. Their grief is pervasive and intense, and lasts longer than most bereaved people normally begin to reengage in life and the grief subsides. People with prolonged grief disorder may show severe emotional pain associated with the death of a loved one, and have difficulty envisioning any future meaning after the person is gone. They may experience difficulties in daily life and may have suicidal ideation or behavior. Some people believe that the death of someone close to them means their own life is over, and there is little they can do about it. They may be hard on themselves and think they should hide their sadness. Friends and family are also distressed because the patient has been thinking only about the deceased and has little interest in current relationships and activities, and they may tell the patient to “forget it” and move on.
Prolonged grief disorder is a new categorical diagnosis, and information about its symptoms and treatment is not yet widely known. Clinicians may not be trained to recognize prolonged grief disorder and may not know how to provide effective treatment or evidence-based support. The COVID-19 pandemic and the growing literature on the diagnosis of prolonged grief disorder have increased attention to how clinicians should recognize and respond to grief and other emotional problems associated with the death of a loved one.
In the 11th Revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11) in 2019, the World Health Organization (WHO) and the American Psychiatric Association (American Psychiatric Association)
In 2022, the Fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) separately added the formal diagnostic criteria for prolonged grief disorder. Previously used terms include complex grief, persistent complex bereavement, and traumatic, pathological, or unresolved grief. Symptoms of prolonged grief disorder include intense nostalgia, pining for, or haunting the deceased, accompanied by other persistent, intense, and pervasive manifestations of grief.
Symptoms of prolonged grief disorder must persist for a period of time (≥6 months according to ICD-11 criteria and ≥12 months according to DSM-5 criteria), cause clinically significant distress or impairment of function, and exceed the expectations of the patient’s cultural, religious, or social group for grief. ICD-11 provides examples of the main symptoms of emotional distress, such as sadness, guilt, anger, inability to feel positive emotions, emotional numbness, denial or difficulty accepting the death of a loved one, feeling a loss of a part of yourself, and reduced participation in social or other activities. The DSM-5 diagnostic criteria for prolonged grief disorder require at least three of the following eight symptoms: intense emotional pain, numbness, intense loneliness, loss of self-awareness (destruction of identity), disbelief, avoidance of things that remind them of loved ones who are gone forever, difficulty reengaging in activities and relationships, and a feeling that life is meaningless.
Studies suggest that an average of 3% to 10% of people who have had a relative die of natural causes suffer from prolonged grief disorder, and the rate is several times higher in people who have had a relative die from suicide, homicide, accidents, natural disasters, or other sudden unexpected causes. In the study of internal medicine and mental health clinic data, the rate reported was more than double the rate reported in the above survey. Table 1 lists the risk factors for prolonged grief disorder and possible indications for the disorder.

Losing someone with whom one is deeply attached forever can be extremely stressful and create a series of devastating psychological and social changes to which the bereaved must adapt. Grief is a common reaction to the death of a loved one, but there is no universal way to grieve or accept the reality of the death. Over time, most bereaved people find a way to accept this new reality and move on with their lives. As people adjust to life changes, they often vacillate between confronting emotional pain and temporarily putting it behind them. As they do so, the intensity of grief diminishes, but it still intermittently intensifies and sometimes becomes intense, especially on anniversaries and other occasions that remind people of the deceased.
For people with prolonged grief disorder, however, the process of adaptation can be derailed, and grief remains intense and pervasive. Excessive avoidance of things that remind them that their loved ones are gone forever, and turning over and over to imagine a different scenario are common obstacles, as are self-blame and anger, difficulty regulating emotions, and constant stress. Prolonged grief disorder is associated with an increase in a range of physical and mental illnesses. Prolonged grief disorder can put a person’s life on hold, make it difficult to form or maintain meaningful relationships, affect social and professional functioning, produce feelings of hopelessness, and suicidal ideation and behavior.

Strategy and evidence

Information about the recent death of a relative and its impact should be part of the clinical history collection. Searching medical records for the death of a loved one and asking how the patient is doing after the death can open up a conversation about grief and its frequency, duration, intensity, pervasiveness, and impact on the patient’s ability to function. Clinical evaluation should include a review of the patient’s physical and emotional symptoms after the death of a loved one, current and past psychiatric and medical conditions, alcohol and substance use, suicidal thoughts and behaviors, current social support and functioning, treatment history, and mental status examination. Prolonged grief disorder should be considered if six months after the death of a loved one, the person’s grief is still severely affecting their daily life.
There are simple, well-validated, patient-scored tools available for brief screening for prolonged grief disorder. The simplest is the five-item Brief Grief Questionnaire (Brief Grief Questionnaire; Range, 0 to 10, with a higher overall score indicating the need for further evaluation of prolonged grief disorder) Score higher than 4 (see supplementary appendix, available with the full text of this article at NEJM.org). In addition, if there are 13 items of Prolonged grief -13-R (Prolonged
Grief-13-R; A score of ≥30 indicates symptoms of prolonged grief disorder as defined by the DSM-5. However, clinical interviews are still needed to confirm the disease. If the 19-item Inventory of Complicated Grief (Inventory of Complicated Grief; The range is 0 to 76, with a higher score indicating more severe prolonged grief symptoms.) Scores above 25 are likely to be the distress causing the problem, and the tool is proven to monitor changes over time. The Clinical Global Impression Scale, which is rated by clinicians and focuses on symptoms associated with grief, is a simple and effective way to assess the severity of grief over time.
Clinical interviews with patients are recommended to make a final diagnosis of prolonged grief disorder, including differential diagnosis and treatment plan (see Table 2 for clinical guidance on the history of death of relatives and friends and clinical interviews for symptoms of prolonged grief disorder). The differential diagnosis of prolonged grief disorder includes normal persistent grief as well as other diagnosable mental disorders. Prolonged grief disorder may be associated with other disorders, especially major depression, post-traumatic stress disorder (PTSD), and anxiety disorders; Comorbidities may also predate the onset of prolonged grief disorder, and they may increase susceptibility to prolonged grief disorder. Patient questionnaires can screen for comorbidities, including suicidal tendencies. One recommended and widely used measure of suicidal ideation and behavior is the Columbia Suicide Severity Rating Scale (which asks questions such as “Have you ever wished you were dead, or that you would fall asleep and never wake up?”). And “Have you really had suicidal thoughts?” ).

There is confusion in media reports and among some health care professionals about the difference between prolonged grief disorder and normal persistent grief. This confusion is understandable because grief and nostalgia for a loved one after their death can persist for a long time, and any of the symptoms of prolonged grief disorder listed in ICD-11 or DSM-5 can persist. Heightened grief often occurs on anniversaries, family holidays, or reminders of the death of a loved one. When the patient is asked about the deceased, emotions may be aroused, including tears.
Clinicians should note that not all persistent grief is indicative of a diagnosis of prolonged grief disorder. In prolonged grief disorder, thoughts and emotions about the deceased and the emotional distress associated with grief can occupy the brain, persist, be so intense and pervasive that they interfere with the person’s ability to participate in meaningful relationships and activities, even with people they know and love.

The basic goal of treatment for prolonged grief disorder is to help patients learn to accept that their loved ones are gone forever, so that they can live a meaningful and fulfilling life without the person who died, and let the memories and thoughts of the person who died subside. Evidence from multiple randomized controlled trials comparing active intervention groups and wait-list controls (i.e., patients randomly assigned to receive active intervention or be placed on a waiting list) supports the efficacy of short-term, targeted psychotherapy interventions and strongly recommends treatment for patients. A meta-analysis of 22 trials with 2,952 participants showed that grid-focused cognitive behavioral therapy had a moderate to large effect on reducing grief symptoms (standardized effect sizes measured using Hedges ‘G were 0.65 at the end of the intervention and 0.9 at follow-up).
Treatment for prolonged grief disorder focuses on helping patients accept the death of a loved one and regain the ability to lead a meaningful life. Prolonged grief Disorder therapy is a comprehensive approach that emphasizes active mindful listening and includes motivational interviews, interactive psychoeducation, and a series of experiential activities in a planned sequence over 16 sessions, once a week. The therapy is the first treatment developed for prolonged grief disorder and currently has the strongest evidence base. Several cognitive-behavioral therapies that take a similar approach and focus on grief have also shown efficacy.
Interventions for prolonged grief disorder focus on helping patients come to terms with the death of a loved one and address the obstacles they encounter. Most interventions also involve helping patients regain their ability to lead a happy life (such as discovering strong interests or core values and supporting their participation in related activities). Table 3 lists the contents and objectives of these therapies.

Three randomized controlled trials evaluating prolongation of grief disorder therapy compared with effective treatment for depression showed that prolongation of grief disorder therapy was significantly superior. Pilot trial results suggested that prolongation of grief disorder therapy was superior to interpersonal therapy for depression, and the first subsequent randomized trial confirmed this finding, showing a clinical response rate of 51% for prolongation of grief disorder therapy. The clinical response rate for interpersonal therapy was 28% (P=0.02) (clinical response defined as “significantly improved” or “very significantly improved” on the Clinical Composite Impression Scale). A second trial validated these results in older adults (mean age, 66 years), in which 71% of patients receiving prolonged grief disorder therapy and 32% receiving interpersonal therapy achieved a clinical response (P<0.001).
The third trial, a study conducted at four trial centers, compared the antidepressant citalopram with placebo in combination with prolonged grief disorder therapy or mourn-focused clinical therapy; The results showed that the response rate of prolonged grief disorder therapy combined with placebo (83%) was higher than that of mournfocused clinical therapy combined with citalopram (69%) (P=0.05) and placebo (54%) (P<0.01). In addition, there was no difference in efficacy between citalopram and placebo when used in combination with mourn-focused clinical therapy or with prolonged grief disorder therapy. However, citalopram combined with prolonged grief disorder therapy significantly reduced concomitant depressive symptoms, whereas citalopram combined with mourn-focused clinical therapy did not.
Prolonged grief Disorder therapy incorporates the extended exposure therapy strategy used for PTSD (which encourages the patient to process the death of a loved one and reduce avoidance) into a model that treats prolonged grief as a post-death stress disorder. Interventions also include strengthening relationships, working within the confines of personal values and personal goals, and enhancing a sense of connection with the deceased. Some data suggest that cognitive-behavioral therapy for PTSD may be less effective if it does not focus on grief, and that PTSD-like exposure strategies may work through different mechanisms in prolonging grief disorder. There are several sadness-focused therapies that employ similar cognitive behavioral therapy and are effective for individuals and groups as well as for prolonged grief disorder in children.
For clinicians who are unable to provide evidence-based care, we recommend that they refer patients whenever possible and follow up with patients weekly or every other week, as needed, using simple supportive measures focused on grief (Table 4). Telemedicine and patient self-directed online therapy may also be effective ways to improve access to care, but asynchronous support from therapists is needed in studies of self-directed therapy approaches, which may be necessary to optimize treatment outcomes. For patients who do not respond to evidence-based psychotherapy for prolonged grief disorder, a re-evaluation should be conducted to identify the physical or mental illness that may be causing the symptoms, especially those that can be successfully addressed with targeted interventions, such as PTSD, depression, anxiety, sleep disorders, and substance use disorders.

For patients with mild symptoms or who do not meet the threshold, and who do not currently have access to evidence-based treatment for prolonged grief disorder, clinicians can help with supportive grief management. Table 4 lists simple ways to use these therapies.
Listening and normalizing grief are core fundamentals. Psycho-education that explains prolonged grief disorder, its relationship to general grief, and what can help often gives patients peace of mind and can help them feel less lonely and more hopeful that help is available. Involving family members or close friends in psychological education about prolonged grief disorder can improve their ability to provide support and empathy for the sufferer.
Making it clear to patients that our goal is to advance the natural process, help them learn to live without the deceased, and address issues that interfere with this process may help patients participate in their treatment. Clinicians can encourage patients and their families to accept grief as a natural response to the death of a loved one, and not to suggest that the grief is over. It is important that patients do not fear that they will be asked to abandon treatment by forgetting, moving on or leaving behind loved ones. Clinicians can help patients realize that trying to adjust to the fact that a loved one has died can lessen their grief and create a more satisfying sense of continuing connection with the deceased.

Domain of uncertainty
There are currently no adequate neurobiological studies that clarify the pathogenesis of prolonged grief disorder, no drugs or other neurophysiological therapies that have been shown to be effective for prolonged grief disorder symptoms in prospective clinical trials, and no fully tested drugs. Only one prospective, randomized, placebo-controlled study of the drug was found in the literature, and as mentioned earlier, this study did not prove that citalopram was effective in prolonging symptoms of grief disorder, but when combined with prolonging grief disorder therapy, it did have a greater effect on combined depressive symptoms. Clearly, more research is needed.
In order to determine the efficacy of digital therapy, it is necessary to conduct trials with appropriate control groups and sufficient statistical power. In addition, the diagnosis rate of prolonged grief disorder remains uncertain due to the lack of uniform epidemiological studies and the wide variation in diagnosis rates due to different circumstances of death.