Naltrexone treatment for prolonged grief disorder: study protocol for a randomized, triple-blinded, placebo-controlled trial

BACKGROUND: There is a lack of effective pharmacotherapy for prolonged grief disorder (PGD). Evidence suggests that the neurobiology of PGD involves the same circuitry as the reward pathway. Based upon this evidence, we hypothesize that PGD can be conceptualized as a disorder of addiction and therefore could benefit from being treated with medications that are currently used to treat such disorders. One such medication is naltrexone, which is currently used to treat alcohol and opioid dependence. Oral naltrexone was chosen for its mechanism of action, safety, and convenience. The primary aim of this study is to establish the efficacy of using oral naltrexone as a pharmacological treatment for PGD. Specifically, we hypothesize that participants receiving naltrexone will demonstrate reduced PGD symptoms when compared to placebo. METHODS/DESIGN: This is a randomized, placebo-controlled, triple-blinded (to healthcare professionals/study staff, participants, and data analysts) study in which we propose to enroll 48 participants who meet criteria for Prolonged Grief Disorder (PGD). Participants will be randomly assigned to the naltrexone 50 mg oral arm or placebo arm; medications will be over-encapsulated to appear identical. Participants will take their assigned medication for 8 weeks, with clinic visits every 4 weeks to assess symptom severity, social closeness, and adverse reactions. Weekly surveys of Prolonged Grief-13-Revised (PG-13-R) will be used to relate naltrexone use to changes in PGD symptom severity. Follow-up 4 weeks after their last visit will assess the longevity of treatment, as well as any lingering adverse reactions. DISCUSSION: This study is the first to investigate the use of oral naltrexone as pharmacological treatment for PGD. The acute and debilitating nature of the disorder, in addition to the increased risk of comorbidities, highlights the need for pharmacological treatment like naltrexone that can act more rapidly, may help those for whom psychotherapy may not be effective, and/or may augment psychotherapy to promote PGD symptom grief resolution. TRIAL REGISTRATION: ClinicalTrials.govNCT04547985. Registered on 8/31/2020.