Journal Article Annotations
2024, 3rd Quarter

Transplant Psychiatry

Annotations by Sarah R. Andrews, MD, Gregory Nikogosyan, DO
October, 2024

Safety of acamprosate for alcohol use disorder Post-Liver transplant: a pilot randomized controlled trial.
Association between psychosocial factors and left ventricular assist device implant outcomes: A systematic review.

PUBLICATION #1 — Transplant Psychiatry

Safety of acamprosate for alcohol use disorder Post-Liver transplant: a pilot randomized controlled trial.

Divya Ayyala-Somayajula, Thomas Bottyan, Suhail Shaikh, Brian P Lee, Stephanie H Cho, Jennifer L Dodge, Norah A Terrault, Hyosun Han.

Abstract: Liver Transpl. 2024 Sep 3. doi: 10.1097/LVT.0000000000000475. Online ahead of print.

Introduction:
Acamprosate is a therapy for alcohol use disorder but data on feasibility and safety in liver transplant (LT) recipients are lacking.

Methods:
This was a single-center unblinded prospective pilot randomized controlled trial of adults (≥18 years) with LT for ALD enrolled between 2021-2023 who were randomized 2:1 to the intervention of acamprosate (666mg dose three times daily) or standard of care (SOC) over 14 weeks. Outcomes included safety [prevalence of adverse events (AE)], feasibility (weekly survey response rate >60%), adherence (self-reported acamprosate use>60%), and efficacy (reduction in Penn Alcohol Craving Scale [PACS]) and relapse-blood phosphatidylethanol≥20ng/mL/reported alcohol use) evaluated by standardized weekly surveys. The efficacy analysis was done in both the intention to treat (ITT) (excluding withdrawals before medication administration) and per-protocol (PP) population (excluding withdrawals/<4 weeks participation).

Results:
Of 78 participants approached, 30 enrolled (19 acamprosate, 11 SOC) with similar baseline characteristics. Eight participants withdrew (6 acamprosate prior to medication administration and 2 SOC). AEs were similar between acamprosate and SOC groups (92.3% vs. 90.0%, p>0.99), including Grade 3 AEs (53.9% vs. 60.0%, p>0.99) with no reported grade 4/5 AEs. Survey response rates were similar in acamprosate vs SOC groups (61.0% vs. 76.0%, p=0.19), and 69.0% were acamprosate adherent. Baseline PACS values were low with no difference by group in median absolute change in PACS for ITT (0, IQR:-4-0 vs. 0, IQR:0-0, p=0.32) and PP analyses (-1, IQR:-6-0 vs. 0, IQR:0-0, p=0.36). There were no reported or biochemical evidence of alcohol relapse.

Conclusion:
In this pilot study, preliminary data suggests that acamprosate may be safe and feasible. These data can inform larger studies and clinician efforts to address alcohol use disorder in post-LT care. (ClinicalTrials.gov, Number: NCT06471686).

Annotation

The finding:
This was a feasibility study examining the use of acamprosate for treating alcohol use disorder in liver transplant patients. During this unblinded prospective pilot project, no significant differences were observed in median AST, ALT, ALP, total bilirubin, BUN, and creatinine levels. Additionally, adverse effects did not significantly differ between patients on acamprosate and those receiving standard care. One individual was discontinued from acamprosate due to diarrhea. The study did not find differences in the efficacy of acamprosate in the post-transplant setting. Survey responses were lower in the acamprosate group, which also demonstrated an adherence rate of 69%.

Strengths and weaknesses:
The strength of this study lies in demonstrating that it is possible to maintain a cohort of liver transplant patients on acamprosate without significant dropouts due to medication side effects or severe events. However, as it was designed as a feasibility study and not powered to assess secondary outcomes, the efficacy of the medication remains unclear.

Relevance:
This study provides further evidence supporting the known clinical understanding that acamprosate is liver-safe, although, according to the package insert, safety is not defined in Child-Pugh Class C patients. This study does not help in determining the superiority of this treatment over other options, given that it is underpowered for determining efficacy as a feasibility study. Considering that liver transplant patients are already on medications contributing to GI side effects, this pilot did show that the GI side effect considerations of acamprosate may impact the initiation of treatment and possibly adherence.

PUBLICATION #2 — Transplant Psychiatry

Association between psychosocial factors and left ventricular assist device implant outcomes: A systematic review.

Joy J Choi, Shreya Bhasin, Johannes Levstik, Patrick Walsh, Mark A Oldham, Hochang Benjamin Lee.

Abstract: Gen Hosp Psychiatry. 2024 Sep-Oct:90:132-140. doi: 10.1016/j.genhosppsych.2024.08.007. Epub 2024 Aug 20.

Abstract

Background:
Psychosocial assessment is a core component of the multidisciplinary evaluation for left ventricular assist device (LVAD) implantation. The degree to which psychosocial conditions are considered a contraindication to LVAD implantation continues to be debated. This systematic review examines modifiable psychosocial factors as predictors of outcomes in patients undergoing LVAD implantation.

Methods:
We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The search resulted in 2509 articles. After deduplication, abstract and full-text review, 20 relevant articles were identified.

Results:
Included studies evaluated socioeconomic status (n = 6), caregiver characteristics (n = 6), non-adherence (n = 6), substance use (n = 13), and psychiatric disorder (n = 8). The most commonly measured outcomes were all-cause death, readmission rate, and adverse events. Studies varied widely in definition of each psychosocial factor and selected outcomes. No psychosocial factor was consistently associated with a specific outcome in all studies. Socioeconomic status was generally not associated with outcomes. Non-adherence, psychiatric disorder, and substance use were associated with higher risks of mortality, adverse events, and/or readmission. Findings on caregiver characteristics were mixed.

Conclusion:
Of the psychosocial factors studied, non-adherence, psychiatric disorder, and substance use were the most consistently associated with an increased risk of mortality, readmission, and/or adverse events. Heterogeneity in research methodology and study quality across studies precludes firm conclusions regarding the impact of psychosocial factors on long-term patient outcomes. The results of this review reveal a need for adequately powered studies that use uniform definitions of psychosocial factors to clarify relationships between these factors and outcomes after LVAD implantation.

Annotation

The finding:
This systematic review assessed how modifiable psychosocial factors affect outcomes for patients receiving left ventricular assist device (LVAD) implants. Following PRISMA guidelines, the review initially considered 2509 articles, eventually focusing on 20 studies that examined factors like socioeconomic status, caregiver characteristics, non-adherence, substance use, and psychiatric disorders in relation to mortality, readmission, and adverse events. The findings indicated that socioeconomic status rarely affected patient outcomes. In contrast, non-adherence, psychiatric disorders, and substance use were often linked to increased risks of mortality, adverse events, and readmissions. The impact of caregiver characteristics was inconclusive. Due to variations in study designs and definitions of psychosocial factors, the review highlighted the need for more uniform and well-powered research to clarify these relationships further after LVAD implantation.

Strengths and weaknesses:
This systematic review offers a comprehensive examination of modifiable psychosocial factors affecting outcomes in LVAD patients, emphasizing its importance in clinical decision-making and patient care. Its strengths lie in the broad inclusion of diverse studies, addressing a significant clinical concern with potential for real-world impact on patient management. However, the review is hindered by several limitations including the inability to establish causality due to the observational nature of data, the lack of standardized definitions across studies for psychosocial variables, and heterogeneous patient populations that might not represent all potential LVAD recipients. Additionally, the findings are often based on self-reported data, which may introduce bias, and many studies do not differentiate between various types and patterns of factors like non-adherence and substance use.

Relevance:
This review holds particular importance for consultation-liaison psychiatrists involved in the care of LVAD patients by elucidating the crucial role of psychosocial factors in patient outcomes. As integral members of the multidisciplinary team, psychiatrists can use these findings to focus on preoperative assessments and tailor ongoing psychosocial interventions, enhancing patient management. The review highlights the need for targeted interventions, such as psychological support and adherence counseling, to improve not only surgical outcomes but also overall quality of life. By offering insights into how psychosocial dynamics influence patient trajectories, the study empowers psychiatrists to better support the complex needs of LVAD patients through proactive and informed care strategies, ultimately fostering more successful outcomes in this challenging patient population.