Pharmacological treatment of bereavement-related distress: a systematic review

Background: With the recent addition of prolonged grief disorder into diagnostic manuals both in the United States (i.e. DSM-5-TR) and internationally (i.e. ICD-11), interest in pharmacologic treatment for grief has increased.Objective: Here, we review how bereavement-related psychological distress, including treating depression secondary to bereavement, has been addressed pharmacologically and the efficacy of these treatments.Methods: Included studies focused on (1) patients bereaved by any cause, (2) patients suffering from bereavement-related mental health problems, and (3) pharmacotherapy interventions to treat those bereavement-related mental health problems. Six databases (MEDLINE, Embase, the Cochrane Library, APA PsycInfo, Scopus, and Web of Science) were searched on 1 October 2020, and updated through 18 December 2024. Studies were selected by two independent reviewers and data were extracted and analysed qualitatively and quantitatively, with meta-analysis performed to calculate standardized mean differences (SMD) of treatment effects. Bias was assessed using the NIH Study Quality Assessment Tools.Results: Thirty-three studies (10 case series/studies, 7 cohort studies, 16 clinical trials) comprising 211,920 participants met eligibility criteria. Of nine medication classes represented, antidepressants were most commonly studied. No medications reduced grief symptomatology across any controlled studies; antidepressants and a beta blocker plus aspirin intervention appeared efficacious for depression symptomatology in bereaved individuals. SMD of effect of pharmacologic intervention on grief over control was negligible (-0.06 [95% CI, -0.31-0.19], data from three studies); SMD of effect of pharmacologic intervention on depression over control was small and not significant (-0.29 [95% CI, -0.68-0.10], data from two studies). Overall, study quality was low.Conclusions: Weak methodology and inconsistent data reporting presented challenges to synthesizing results. There is no evidence to support the use of current pharmacologic treatment for prolonged grief disorder, highlighting the need for further research to fill this gap in treatment options.