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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 4  |  Issue : 1  |  Page : 15-20

Complicated grief and its pharmacological management


1 Department of Psychiatry, Indira Gandhi Institute of Medical Sciences, Patna, India
2 Department of Psychiatry, All India Institute of Medical Sciences, Patna, India

Date of Web Publication10-Dec-2020

Correspondence Address:
Rajesh Kumar
Department of Psychiatry, Indira Gandhi Institute of Medical Sciences, Patna
India
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Source of Support: None, Conflict of Interest: None


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  Abstract 


Introduction : Complicated grief is a debilitating illness with millions of people suffering from this condition globally. In Indian setting, where still the majority of such patients are being seen by primary care physicians, it is imperative for clinicians to understand the phenomenology of grief and to provide evidence-based pharmacotherapy only to those who need it.
Materials and Methods : A literature search was done in Pubmed database using the keywords: complicated grief, traumatic grief, prolonged grief. Research articles of pharmacological treatment of complicated grief were also included.
Discussion : Various terms related to grief like; bereavement, traumatic grief, prolonged grief as well as the recently introduced terms Persistent complex bereavement disorder (PCBD) and prolonged grief disorder (PGD) were discussed and differentiated. The pharmacological trials targeting complicated grief were also highlighted.
Conclusion : Although psychotherapeutic options are available for complicated grief, but there is a need to study drugs of better safety and efficacy profile to be able to provide faster relief to the ever increasing population of persons with complicated grief.

Keywords: Complicated grief, Grief, Management, Pharmacotherapy


How to cite this article:
Kumar R, Jha VN. Complicated grief and its pharmacological management. J Indira Gandhi Inst Med Sci 2018;4:15-20

How to cite this URL:
Kumar R, Jha VN. Complicated grief and its pharmacological management. J Indira Gandhi Inst Med Sci [serial online] 2018 [cited 2022 Jan 20];4:15-20. Available from: http://www.jigims.co.in/text.asp?2018/4/1/15/302977




  Introduction : Top


The death of a loved one is a very stressful event in an individual’s life and death of spouse has been considered the worst ‘Life event’, being given maximum point of 100 Life change units (LCU).[1] Grief is the psychobiological response to such loss and is considered as a normal, universal experience with progression through successive stages as described by several authors.[2],[3] The most common experience has been termed ‘Normal Grief’ and it progresses from an initial phase of Acute grief to a later phase of Integrated Grief over several months.[4],[5],[6] It is said that grief never resolves completely, but most people learn to cope up with the new reality and lead a functionally productive and satisfying life. However, a subset of people fail to cope up properly and enter a phase of ‘Complicated grief’.[7] Complicated Grief (CG), which was earlier known as ‘Traumatic grief’, is a condition in which proper healing has been impaired and results in intense and prolonged phase of acute grief.[8] Complicated grief is a source of significant distress and is co-morbid with other psychiatric conditions.[9] It has negative consequences on physical health of the individual,[10],[11] including on children after parental deaths.[12] The prevalence of complicated grief has been reported to be varying from 7% to 20%.[13],[14],[15] The Indian census data of 2011 showed the crude death rate of 7 per 1000 people with a total population of 1.19 billion.[16] Hence it can be said that around 9 million people die every year in India. Antonucci et al, 2004 have estimated that each death leaves around one to five people bereaved suggesting that, in India around 5 million people can be expected to develop complicated grief each year.[17] Moreover, given the poor doctor to patient ratio in India (two psychiatrists per 10 lakh population) more patients are likely to be seen by primary care physicians.[18] Hence it is imperative for clinicians to be aware of the process of grief, to be able to differentiate similar terminologies and to understand how a ‘normal’ grief can get abnormal and complicated. We therefore present a complete understanding of complicated grief and a review of the available pharmacotherapy options.


  Materials and Methods : Top


A literature search was done in Pubmed and MEDLINE databases without keeping any time limit for published articles. The following keywords were used: grief, bereavement, complicated grief, traumatic grief, prolonged grief. The search results included review articles, drug trials, edited books etc. treatment studies targeting complicated grief were also included in the review. Additional search and citations were done using the references of selected articles.


  Discussion : Top


NORMAL GRIEF

George Engel in his seminal paper in 1961 had drawn a corollary between grief and injury or infection.[19] An injury or infection is akin to the death of someone, and the process of grief is similar to the inflammatory process which gets started in such an event. Both these processes are universal and considered normal with majority of the people returning to a previous state of health. However, there may be complications to the process of healing leading to delay in wound healing or superimposed infections. Similarly, grieving process may get complicated in terms of prolongation of the grief phase and/or morbid changes in mood, perception and cognition.[20]

At the start few terminologies related to grief need to be clarified. Bereavement refers to the experience of having lost someone. The term Grief is used to refer to the emotional, cognitive and behavioural responses to the death. Mourning is also interchangeably used to refer to the above two terms, but it usually refers more specifically to only the behavioural responses of grief and is influenced by the prevailing socio-cultural context. The normal grieving process has been traditionally described to be evolving through five successive stages: Denial, Anger, Bargaining, Depression and Acceptance.[3] However, normal grief can be seen to consisting of two forms; acute and Integrated grief. The symptomatology of acute grief was first described by Erich Lindemann in 1944 after the Coconut grove fire in Boston.[21] He described six components of acute grief: a) Intense somatic distress, b) Thoughts of the deceased preoccupy the survivor, c) guilt and self-accusations, d) irritation and anger directed at everyone, e) restlessness, agitation, lack of motivation, f) identification with the deceased. Acute grief can vary in intensity, nature and can include a mix of positive and negative emotions as well as oscillations between different states over time.[22] Although the precise duration for which this phase will last is debated, but longitudinal studies have proposed a six to twelve month period over which majority of people would have moved to a phase of Integrated grief.[23],[24],[25] In integrated grief, the deceased are easily called into mind with some sadness and longing, but these feelings become less intense. These feelings do not preoccupy the mind or disrupt the daily functioning, except during anniversaries, holidays or other reminders of the loss.


  Abnormal Grief : Top


Whenever the normal healing process gets disrupted, a condition of abnormal grief results. Over the years, this abnormal grief has been denoted by several similar terms like: chronic, delayed, atypical, distorted, traumatic, unresolved, morbid, complicated etc.[10],[26],[27] However the clinical description of each of the above terms is about the same. Singh et al,1980 had classified two categories of morbid grief reactions; pathological and complicated.[28] They proposed that pathological grief is the presentation of symptoms similar to normal grief, although in an exaggerated manner, while complicated grief is the presentation with idiosyncratic symptoms of a neurotic or psychotic illness, in addition to grief reaction.

With the arrival of Diagnostic and Statistical Manual (DSM 5) and drafting of International Classification of Diseases (ICD 11), new terms related to abnormal grief has come to attention; namely prolonged grief disorder (PGD), complicated grief (CG) and persistent complicated bereavement disorder (PCBD). Prolonged grief disorder (PGD) first proposed by Prigerson et al, 2009 is characterised by intense grief which is prolonged, lasting beyond six months post-loss.[24] In this the symptoms are not atypical, rather the symptoms remain too intense for far too long. Hence, the pathology is not in the symptoms as such but their duration. PGD is being proposed for adoption as a diagnosis in ICD 11, in a shorter version.[29] Complicated grief (CG) emerges from the concept of depression as a result of bereavement-related complication and it has been re introduced by Shear et al, 2011.[30],[31] It highlights the fact that there are complications in bereavement that needs to be addressed like, depression, trauma that hinders the successful resolution of grief. DSM 5 has introduced the term persistent complicated bereavement disorder (PCBD) which has not been given full diagnostic category status because it was evaluated as requiring further research.[32] It has not included the term ‘grief’ in its nomenclature thereby avoiding the comment on the fact whether grief is pathological or not. It emphasises the fact that the course of grief can be inherently pathological. Also the duration criterion requires symptoms to be present beyond 12 months and hence PCBD appears to lie somewhere between PGD and CG. Maciejewski et al, 2016 have compared the diagnostic specificity and predictive validity of the symptom diagnostic tests for PGD and PCBD and found that these tests identify the same diagnostic entity and the difference between them is mainly semantic.[33] Since PCBD has been recently introduced in DSM5, PGD is yet to be included in ICD-11 and majority of the research is available on ‘complicated grief’, we would be discussing CG in the following sections.

Complicated Grief

Hartz et al, 1986 first proposed CG as a diagnostic entity in DSM IV and Horowitz et al, 1997 tested its diagnostic criteria in their seminal paper.[7],[34] The prevalence of CG varied in different studies depending on the sample characteristics and applied criteria. It was 2.4% in Japan,[35] 3.7% in Germany[15] and 4.2 % in Switzerland.[36] Shear et al,2005 found the prevalence to be up to 10 % of bereaved people.[14] It is characterised by dysfunctional thoughts, maladaptive behaviours and emotional dysregulation. The individual may experience recurrent thoughts and images of the deceased, troubling ruminations about the circumstances of death and persistent feelings of shock, disbelief and hopelessnes.[37] Burton et al,2012 found less ‘forward coping’ in patients with CG, which they defined as the ability to think optimistically, maintain calm, be able to plan ahead and attend to the needs of others.[38] CG also affects the physical health of an individual as observed by reduced quality of life, increased risk of cardiovascular illness, sleep disturbance, increased risk of suicide.3[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[44]

CG may share several features with depressive episode (MDD) and post traumatic stress disorder (PTSD). Features similar to depressive episode are sadness of mood, loss of interest and guilt. Whereas, sense of shock, intrusive images and avoidance may mimic PTSD.[45] However there are several differences that make CG a distinct disorder.

Differences with depression

Yearning symptoms are at the core of CG, while depressed mood is the core feature of MDD. There is pervasive sadness of mood and complete anhedonia in MDD, while sadness is focussed on missing the deceased and the interest in the memories of the deceased is maintained in CG. A depressed person ruminates over past deeds with a pervasive sense of guilt, whereas a grieved person is preoccupied with positive thoughts of the deceased and guilt is related to the circumstances of death. The duration criteria for the two disorders also varies.[46],[47]

Differences with PTSD

PTSD is triggered by a life threatening event, while CG is triggered by a loss. The hallmark symptoms of CG are the yearning symptoms with the primary emotion being of sadness, but intrusive symptoms are at core in PTSD with fear being the chief emotion. PTSD people avoid places considered to be dangerous while people with CG avoid places or situations likely to remind the deceased.[48],[47],[48],[49],[50]

Risk Factors

The risk factors of CG can be subdivided into pre loss, loss related and peri-loss factors.

Pre loss factors that have been implicated as risk factors are; female gender, history of mood disorder, pre-existing trauma (especially childhood trauma), history of prior loss, insecure attachment, pessimistic temperament and personality traits.[51],[52],[53],[54],[55],[56],[57]

Loss related factors: nature of death being violent, acute; chronically ill and identity defining loss.[58],[59], [60,[61]

Peri-loss factors: social circumstances, low perceived support, interference with natural healing like inability to follow usual mourning process and cognitions during bereavemen[62],[63]

Screening

There are some tools for screening of CG in bereaved people. Inventory of complicated grief (ICG) is a 19 item self rated tool for screening, with scores in the range of 25 to 30 are associated with significant symptoms.[51],[64] Brief grief questionnaire is a 5 item screening test that can be used in primary care setting as well.[65]

Diagnostic Validators

There are certain diagnostic validators which can be useful in helping to differentiate complicated grievers from normal ones. On functional imaging study of brain, there is activation of nucleus accumbens on exposure to cues related to the deceased.[66] CG was associated with a MAO- A variant in patients with depression.[67] Heart rate response showed a reduction in rate when discussing about the loss in CG patients while there was a rise in heart rate in patients with PTSD.[68] Deficits in specific autobiographic memory functions is also noticed in CG.[69]


  Treatment : Top


There is a considerable debate about attempting to diagnose CG and later discussing its treatment options. However, it must be noted that bereavement causes a great risk of mortality in the survivors in the early period of grief. The mortality is primarily due to suicides, accidents, heart diseases etc.[70] Hence, providing the grievers with early intervention seems paramount. Psychotherapeutic interventions like Interpersonal therapy, Cognitive behaviour therapy have been used as a first line measure but of late various pharmacological agents have also been studied.[71] The various situations that merit starting pharmacological intervention are: persistently high symptom severity, suicidal ideations, functional impairment, and hopelessness among others. We shall be discussing only the Pharmacological options.

a. Bereavement related depression

Initial research on pharmacotherapy in bereaved people involved cases with bereavement related depression. The first research was done by Jacobs et al, 1987 which was an open label trial with tricyclic antidepressant (TCA) Desipramine (75 to 150 mg/day).[72] Ten cases (eight widows and two widowers) with age range 25-65 years were administered this drug for four weeks period. Seven out of ten (70%) cases reported improvement in depressive symptoms on Clinician Global Impression- Improvement scale (CGI-I), while about 37.5% reported improvement in grief symptoms also.

Pasternak et al, 1991 conducted another open label trial, but with another tricyclic agent Nortriptyline (mean dose 49.2 mg/day).[73] Sample included 13 bereaved spouses (61% women) with mean age 71 years and time since loss 11.9 months median. They were given nortriptyline for a median period of 6.4 weeks. There was 68 % improvement in depressive symptoms when assessed by Hamilton depression rating scale (HDRS) and Beck’s Depression Inventory (BDI), but only 9 % improvement in grief symptoms on Texas revised Inventory of grief (TRIG).[74],[75],[76]

Zisook et al, 2001 researched newer antidepressant, Bupropion (150-300 mg/day).[77] In this open label trial, recently bereaved people (time since loss 8 weeks) were given this drug for a period of 8 weeks. There were 73% women in the sample with mean age 63.5 years. The study completers (n = 14) showed 73% improvement in depressive symptoms as measured on HDRS and 22% improvement in grief symptoms as measured on Inventory for complicated grief.

In the only randomised controlled trial of medication use in bereavement related depression, Reynolds et al 1999 randomised 80 people (72% women, mean age 66 years) in to four groups.78 Nortriptyline alone (n=25), placebo alone (n=22), nortriptyline plus interpersonal therapy {IPT} (n=17) and placebo plus IPT (n=16). The mean dose of Nortriptyline given was 66mg/day. Participants were recruited within 8 months of loss and were required to have major depressive disorder (MDD) plus TRIG score of more than 45 for grief symptom severity. After the end of 16 weeks of intervention, the improvement in depressive symptoms was maximum (69%) in the nortriptyline plus IPT group, followed by nortriptyline alone (56%), placebo (45%) and placebo plus IPT (29%). However, in terms of grief symptoms no differential effect of treatment was seen.

b. Pharmacotherapy for Complicated grief

The paucity of literature on pharmacotherapy of complicated grief is due to the prevalent confusion in nomenclature. The DSM 5 has recently included persistent complex bereavement disorder (PCBD) in its diagnostic system but kept it under conditions requiring further research. ICD 11 is proposing a criterion named prolonged grief disorder (PGD). Hence following a review of the available pharmacological trials in cases of complicated grief.

Zygmont et al. 1998 conducted an open label trial for a selective serotonin reuptake inhibitor (SSRI) Paroxetine (10 to 50 mg/day) that was administered to 21 people with traumatic grief (earlier term for complicated grief).[79] 13 patients (mean age 57 years) eventually completed the full trial of 16 weeks. The improvement as measured by ICG on grief intensity was 48% and by HDRS on depression was 51%. The authors then did a post-hoc comparison of paroxetine in this study with nortriptyline in another ongoing study (n=18 for 16 weeks) and found similar reductions in severity scores of both depression and grief, although depressive symptoms responded earlier than grief symptoms.

Shear et al, 2006 in their open label trial on CG patients (mean 3.9 years after loss) used another SSRI, Escitalopram (10 to 20 mg/day).[80] 17 patients with ICG score more than 30 were treated for a period of 16 weeks and at the end a response of 24% was observed in grief symptoms.

In a recent open label trial in 2009 involving 30 patients with MDD and CG, Escitalopram was given at a dose 10 to 20 mg/day.[81] Only 14 out of these had CG in addition to MDD, rest having only MDD. The time since loss was less than 6 months in the participants and the treatment was given for 12 weeks. There was an improvement of 21% in grief symptoms as per the ICG score.

Simon et al, 2007 presented a case series involving four women (mean age 41years) with a diagnosis of CG (ICG score ≥ 30, within 6 months of loss).[82] All were given Escitalopram (10 to 20 mg/day) and at the end of 10 weeks, they had shown significant improvement (76%) in grief symptom scores.

One RCT investigated the role of benzodiazepine in the management of recent grief.[83] Participants were randomised between Diazepam (2mg/day) and placebo to be used on sos basis for 6 weeks. At the end of 7 month of follow up, no significant differences between the two groups was seen in terms of grief scores.

c. Combined psychotherapy and phamacoherapy

Reynolds et al, 1999 in their RCT, failed to show any significant change when medication (Nortriptyline) was combined with psychotherapy (IPT).[78]

Shear et al conducted a RCT in which they compared the efficacy of Complicated grief therapy (CGT) and interpersonal threrapy (IPT).[84] However, the authors allowed medications during the course of therapy on which the patient had been stable for a minimum of three months. The study concluded that the use of medication was marginally associated with better response in both the arms of therapy.

Simon et al in their follow up analysis concluded that patients with complicated grief who were on a stable dose of antidepressant medication were two times likely to be treatment responders.[85]

In all of the studies discussed above, it was evident that the depressive symptoms responded earlier than grief symptoms and the magnitude of response was also large as compared to the latter. Reynolds et al,1999 have proposed two possible explanations for this.[78] The first one being that depressive symptoms may reflect biological dysregulation which is more amenable to biological therapies, while persistent grief symptoms are due to unresolved aspects of loss. The second explanation could be that grief symptoms are not always pathological or abnormal.


  Conclusion : Top


The available trials suggest that the pharmacological interventions indeed has a good role to play in the management of complicated grief. Antidepressants use has been shown to reduce both depressive and grief related symptoms. In addition to that, use of antidepressants has been shown to make psychotherapeutic interventions more effective. In the majority of the trials SSRIs and TCAs have been used, though newer antidepressants have yet to be used. Further studies evaluating different neurotransmitters and neural pathways are needed as well as RCTs involving newer drugs. Clinicians need to acquaint themselves to the new researches going on in this field in order to provide good care to their patients.



 
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