Michael Joshua Ostacher

Objectives: Alcohol-related liver disease is the primary indication for liver transplantation, yet posttransplant outcomes among recipients with an alcohol use disorder (AUD) diagnosis remain inconsistent. This study assesses whether AUD is associated with adverse liver transplantation (LT) outcomes after adjustment for clinical and sociodemographic factors. Methods: We conducted a retrospective cohort study of adult LT recipients (2015–2024) using a nationally representative electronic health record database (Atropos). Recipients with AUD within 1 year before transplantation were compared with recipients without the diagnosis. Outcomes included mortality, graft rejection, and hospitalization. Confounding was addressed using unmatched analyses, demographic matching, and high-dimensional propensity score matching (HDPSM). One-year outcomes were assessed with odds ratios (ORs) and long-term outcomes with Cox models and Kaplan-Meier analyses. Results: Among 24,865 recipients of LT, the ones who had an AUD diagnosis (n=2393) presented an association with higher posttransplant mortality across all analytic approaches. In the adjusted HDPSM analysis, AUD was associated with increased 1-year mortality (OR: 3.20, 95% CI: 1.81–5.64) and greater long-term mortality risk (HR: 1.81, 95% CI: 1.24–2.62). Elevated risks of graft rejection and hospitalization were observed in less-adjusted models; however, these associations were no longer statistically significant after HDPSM adjustment (eg, 1-y graft rejection OR: 1.13, 95% CI: 0.85–1.48; long-term hospitalization HR: 0.91, 95% CI: 0.78–1.05). Conclusions: AUD is associated with increased post-LT mortality even after adjustment. Differences in graft rejection and hospitalization were attenuated after HDPSM, suggesting influence from comorbidity and health care utilization rather than AUD alone.

Background and Aims: Unhealthy alcohol use is prevalent in chronic liver disease (CLD). This randomized controlled trial evaluated the efficacy of telehealth stepped alcohol treatment (SAT) in three healthcare systems. Approach and Results: Participants (N=157) with CLD and unhealthy alcohol use (>7 drinks/week or ≥4/day for women; >14/week or ≥5/day for men; or heavy episodic drinking, using timeline follow back), were enrolled at a safety-net and 2 Veterans Affairs hepatology clinics from 3/1/2022-2/28/2024. Participants were randomized to SAT (N=81; Step 1: three motivational interviewing sessions, Step 2: addiction medicine referral if no drinking reduction at month 3) or usual care (UC; N=76); evaluated at months 3 and 6. Alcohol use reduction was analyzed using bivariate tests and multivariable modeling. Baseline characteristics were: median age 61, 86% male, 48% with cirrhosis (37% decompensation), and 78% with alcohol use disorder. Compared to UC, SAT had no difference in percentage of alcohol use below moderate level (primary outcome) but had greater reduction in drinks/week from baseline to month 3 (estimate -0.66, P =0.03) and month 6 (estimate -0.67, P =0.03) (secondary outcome). The 6-month effect of SAT (vs UC) on alcohol use reduction remained significant ( P =0.02), controlling for covariates. At month 6, 30-day abstinence rates were 29% for SAT and 18% for UC ( P =0.14). Baseline motivation to reduce alcohol use was positively associated with treatment response. Conclusions: SAT was not superior on the primary outcome, yet reduced alcohol use more than UC at six months in this difficult-to-engage population and may be valuable in hepatology.

Summary: The American Society of Clinical Psychopharmacology convened a 45-member international expert task force to identify circumstances supporting the deprescribing of core psychotropic medications for major depressive disorder (MDD) and bipolar disorders. Three Delphi survey rounds plus a selective literature review identified points of consensus (predefined as ≥75% agreement) about when antidepressant, antipsychotic, mood stabiliser and sedative-hypnotic deprescribing is warranted. Twenty out of 32 statements (63%) achieved consensus across seven thematic areas. In MDD, panellists favoured discontinuing antidepressants when mechanisms of action are duplicative, adequate trials produce ≤25% improvement or loss of prior efficacy cannot be regained through dose increases or augmentations. Indefinite antidepressant maintenance in MDD was favoured after three or more lifetime episodes. In bipolar disorder, antidepressant deprescribing was favoured in the setting of rapid cycling, mixed features or emerging mania/hypomania symptoms; and discouraged if prior antidepressant cessation led to relapse. In nonpsychotic mood disorders, panellists favoured deprescribing antipsychotics that caused significant weight gain or tardive dyskinesia over adding pharmacological antidotes. Deprescribing to achieve an eventual medication-free status was considered inappropriate, in bipolar type 1, but not necessarily bipolar type 2 disorder. Although individualised circumstances necessarily inform psychopharmacology management, clinical presentations that misalign with existing pharmacotherapies may signal the desirability of cautious deprescribing.

Background: Sleep pattern alteration is a core feature of bipolar disorder (BD), often challenging to treat and affecting clinical outcomes. Suvorexant, a hypnotic agent that decreases wakefulness, has shown promising results in treating primary insomnia. To date, data on its use in BD are lacking. This study evaluated the efficacy and tolerability of adjunctive suvorexant for treatment-resistant insomnia in BD patients.Methods: Thirty-six BD outpatients (19 BDI, 69.4% female, 48.9 [±15.2] years) were randomized for 1 week to double-blind suvorexant (10–20 mg/day) versus placebo. Then, all subjects who completed the randomized phase were offered open suvorexant for 3 months. Subjective total sleep time (sTST) and objective total sleep time (oTST) were assessed.Results: During the randomized control trial (RCT) phase, an overall increase in the oTST emerged, which was statistically significant for the Cole–Kripke algorithm (p = 0.035). The comparison between the suvorexant and placebo groups was limited by significant differences between measurements at baseline. During the open phase, no significant improvement was detected relative to either sTST and oTST. No adverse events nor major intolerances were reported.Discussion: Efficacy results are inconsistent. During the RCT phase, only a small increase in the objective oTST emerged, while during the open phase, no significant improvement was detected. While this is the first ever study of suvorexant in BD-related insomnia, the limitation of the small sample and the high rate of dropouts limits the generalizability of these findings. Larger studies are needed to assess suvorexant in treating BD-related insomnia.

Management of depressive episodes in bipolar disorder remains challenging for clinicians despite the availability of treatment guidelines. In other contexts, large language models have yielded promising results for supporting clinical decisionmaking. We developed 50 sets of clinical vignettes reflecting bipolar depression and presented them to experts in bipolar disorder, who were asked to identify 5 optimal next-step pharmacotherapies and 5 poor or contraindicated choices. The same vignettes were then presented to a large language model (GPT4-turbo; gpt-4-1106-preview), with or without augmentation by prompting with recent bipolar treatment guidelines, and asked to identify the optimal next-step pharmacotherapy. Overlap between model output and gold standard was estimated. The augmented model prioritized the expert-designated optimal choice for 508/1000 vignettes (50.8%, 95% CI 47.7–53.9%; Cohen’s kappa = 0.31, 95% CI 0.28–0.35). For 120 vignettes (12.0%), at least one model choice was among the poor or contraindicated treatments. Results were not meaningfully different when gender or race of the vignette was permuted to examine risk for bias. By comparison, an un-augmented model identified the optimal treatment for 234 (23.0%, 95% CI 20.8–26.0%; McNemar’s p < 0.001 versus augmented model) of the vignettes. A sample of community clinicians scoring the same vignettes identified the optimal choice for 23.1% (95% CI 15.7–30.5%) of vignettes, on average; McNemar’s p < 0.001 versus augmented model. Large language models prompted with evidence-based guidelines represent a promising, scalable strategy for clinical decision support. In addition to prospective studies of efficacy, strategies to avoid clinician overreliance on such models, and address the possibility of bias, will be needed.

Dr Ostacher discusses a review by Rodas et al and points to a need for clear answers on how best to advise patients with PTSD and other psychiatric illness about cannabis use.

Background: Management of cirrhosis is challenging and has been complicated by the COVID-19 pandemic due to decreased access to care, increased psychological distress, and alcohol misuse. Recently, The National Institute on Alcohol Abuse and Alcoholism has broadened the definition of recovery from alcohol use disorder to include quality of life (QoL) as an indicator of recovery. This study examined the associations of alcohol-associated cirrhosis etiology and problematic drinking with liver disease QoL (LDQoL). Methods: Patients with cirrhosis (N=329) were recruited from 3 sites (63% from 2 Veterans Affairs Health Care Systems and 37% from 1 safety net hospital) serving populations that are economically or socially marginalized. Cirrhosis etiology was ascertained by chart review of medical records. Problematic drinking was defined by ≥8 on the Alcohol Use Disorders Identification Test. Multivariable general linear modeling adjusting for age, sex, race/ethnicity, site, pandemic-related stress, and history of anxiety/depressive disorder were conducted. Sensitivity analyses further adjusted for indicators of liver disease severity. Results: Participants were on average 64.6 years old, 17% female, 58% non-White, 44% with alcohol-associated cirrhosis, and 17% with problematic drinking. Problematic drinking was significantly associated with worse LDQoL scores in the overall scale and in the memory/concentration and health distress subscales. These associations remained significant after adjusting for indicators of liver disease severity, including Model for End-Stage Liver Disease-Sodium score and decompensated cirrhosis status. Conclusions: Among patients with cirrhosis, problematic drinking was associated with worse LDQoL, especially in the domains of memory/concentration and health distress. Assessment and awareness of cognitive deficits and negative emotionality within the context of cirrhosis and problematic drinking may help clinicians provide better integrated care for this population. Export