Clinical implications of co‐occurring prolonged grief disorder in patients with treatment‐resistant major depressive disorder

Prolonged grief disorder (PGD) is now an official diagnosis in both the ICD‐11 and the DSM‐5‐TR ¹ . It is a distressing and disruptive condition that often occurs concomitantly with depressive and other psychiatric disorders, yet the consequences of this comorbidity are not fully understood ² . We examined the importance of co‐occurring PGD in a large sample of patients with treatment‐resistant major depressive disorder (TRD).

The VA Augmentation and Switching Treatments for Depression (VAST‐D) Cooperative Study included 1,522 psychiatric outpatients with TRD (85.2% males; 69.2% White, 25.6% African American; mean age 54.4±12.2 years) who were randomized to switch the index antidepressant to bupropion SR, combine the index antidepressant with bupropion SR, or augment with aripiprazole ³ . Of these patients, 1,416 (93.0%) had experienced the death of a loved one in their lifetime. The mean time since the death was 11.9 years, yet 600 (42.4% of the bereaved) felt that their grief still interfered, at least somewhat, with their lives.

The study's primary outcome, remission, was operationalized as a 16‐item Quick Inventory of Depressive Symptomatology‐Clinician Rated (QIDS‐C₁₆) ⁴ score of ≤5 at two consecutive visits during the 12‐week acute treatment phase. Suicide risk was assessed with the Columbia‐Suicide Severity Rating Scale (C‐SSRS) ⁵ both at baseline and at the end of the acute treatment phase. For this report, we utilized the number and percentage of participants who endorsed recent (within the past 3 months) passive suicidal ideation (e.g., wish to be dead) and active suicidal ideation (actual intent and/or plan).

At the baseline visit, bereaved VAST‐D participants completed the 5‐item self‐rated Brief Grief Questionnaire ⁶ (difficulty accepting the death, grief interfering with life, intrusive thoughts of the person or the death, avoiding reminders of the loss, and feeling cut off or distant from others) and two additional items for yearning and grief intensity. Each of the seven items was rated on a 3‐point scale: 0 = not at all, 1 = somewhat, 2 = a lot.

According to the ICD‐11 ⁷ , a PGD diagnosis was assigned when a participant indicated all of the following: a) time since death of the loved one ≥6 months; b) endorsed “a lot” on at least one of the following: grief intensity or yearning for the deceased; c) endorsed “a lot” on at least one of the following: trouble accepting the death, troublesome images of the lost person or his/her death, avoiding reminders, feeling cut off or distant from others; d) endorsed “somewhat” or “a lot” on “grief continues to interfere with life”. Participants fulfilling these requirements were 276 (19.5% of the bereaved). Patients bereaved >6 months without PGD were categorized as “ordinary long‐term grief” (N=1,041, 73.5%). Those bereaved less than 6 months were categorized as “acute grief” (N=99, 7.0%).

PGD was significantly more common among African American bereaved participants (96/343, 28.0%) than White ones (145/948, 15.3%) (X²=37.26, p<0.0001). There were no differences between bereaved participants with and without PGD on age, gender, employment, age of first treatment for depression, or duration of current episode. Time since the death of the loved one was not significantly different between those with PGD and those with ordinary grief.

Among participants bereaved >6 months, those with PGD were more likely to feel that their depression was related to their grief. They had at baseline significantly more severe depression on the QIDS‐C₁₆ (p<0.0001), more anxiety on the Beck Anxiety Scale (p<0.0001), worse quality of life on the Quality of Life Enjoyment and Satisfaction Questionnaire (p<0.0001), more passive and active suicidal ideation on the C‐SSRS (p<0.05), and more post‐traumatic stress disorder on the Mini International Neuropsychiatric Interview (p<0.0001). In addition, they had experienced more early childhood life adversity as assessed by Adverse Childhood Experiences Survey (ACES) (p<0.0001).

Remission of depression at the end of the treatment period was significantly less likely in patients with PGD (N=50, 18.1%) than in those with ordinary long‐term grief (N=296, 28.4%) and those with acute grief (N=20, 20.2%) (X²=13.9, p<0.001). Also, with or without depression remission, active suicidal plans and/or intent at the end of the treatment period were more frequently reported in patients with PGD (N=13, 4.7%) than in those with ordinary long‐term grief (N=15, 1.4%) and those with acute grief (N=3, 3.0%) (X²=11.2, p<0.01).

To our awareness, this is the first study to systematically assess the effects of co‐occurring grief in a large sample of patients with treatment‐resistant depression. We found that patients with co‐occurring PGD were less likely to remit from their depressive episode than patients with ordinary long‐term grief. Those with acute grief were somewhere in between the two other groups. The same pattern was true for active suicidal ideation.

These findings underscore the importance of an accurate diagnosis of PGD in patients with treatment‐resistant depression, so that targeted clinical attention can ensue. The only study assessing the effects of antidepressants in depressed patients with or without PGD found that medications relieved depressive symptoms in those with PGD, but only if they were also receiving a grief‐targeted psychotherapy ⁸ . This suggests that patients with treatment‐resistant depression who also have PGD would greatly benefit from a grief‐focused intervention in addition to the depression‐focused treatment.