A Randomized, Double-Blind, Placebo-Controlled Pilot Trial of the Acute Antisuicidal and Antidepressant Effects of Intranasal (R,S)-Ketamine in Severe Unipolar and Bipolar Depression With and Without Comorbid Alcohol Use Disorder.

Objective: Although individuals with a family history of alcohol use disorder (AUD) have a superior antidepressant response to ketamine, outcomes in patients with current AUD remain unclear. This study sought to investigate whether intranasal (IN) racemic (R,S)-ketamine had antisuicidal and antidepressant effects in unipolar and bipolar depression and whether comorbid AUD conferred superior antisuicidal outcomes for patients.Methods: This was a double-blind, randomized, placebo-controlled trial (May 2018 to January 2022) of single administration, fixed-dose (50 mg) IN (R,S)-ketamine (or saline comparator) in unmedicated inpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, criteria for a current major depressive episode (bipolar or unipolar), with current suicidal ideation (SI) and past attempt. Patients with and without comorbid AUD were enrolled. Change in Scale for Suicide Ideation score was the primary outcome measure, and change in Montgomery-Åsberg Depression Rating Scale score was the secondary outcome measure.Results: No significant group × time effect was noted for SI (F = 1.1, P = .36). A statistical trend toward superior improvement in suicidality was observed in participants with comorbid AUD. The group × time interaction was significant for improvements in depression (F = 3.06, P = .03) and largely unaffected by comorbid AUD or primary mood disorder type. Within the ketamine group, a significant correlation was observed between improvement in depressive symptoms and SI for patients without comorbid AUD (r =0.927, P = .023) that was absent in patients with AUD (r = 0.39, P = .44).Conclusion: IN ketamine induced rapid antidepressant effects compared to placebo but did not significantly alter SI scores. The treatment was well tolerated. Continued investigation with IN ketamine as a practical alternative to current formulations is warranted.Trial Registration: ClinicalTrials.gov identifier: NCT03539887.

The Role of the Gut Microbiome in Bipolar Disorder and its Common Medical Comorbidities.

Bipolar disorder is a decidedly heterogeneous and multifactorial disease, with significant psychosocial and medical disease burden. Much difficulty has been encountered in developing novel therapeutics and objective biomarkers for clinical use in this population. In that regard, gut-microbial homeostasis appears to modulate several key pathways relevant to a variety of psychiatric, metabolic, and inflammatory disorders. Microbial impact on immune, endocrine, endocannabinoid, kynurenine, and other pathways are discussed throughout this review. Emphasis is placed on this system's relevance to current pharmacology, diet, and comorbid illness in bipolar disorder. Despite the high level of optimism promoted in many reviews on this topic, substantial obstacles exist before any microbiome-related findings can provide meaningful clinical utility. Beyond a comprehensive overview of pathophysiology, this review hopes to highlight several key areas where progress is needed. As well, novel microbiome-associated suggestions are presented for future research.

Current curricular trends after the COVID-19 pandemic: A national survey of psychiatry residency programs.

OBJECTIVES: During the COVID-19 pandemic, many psychiatry residencies (academic, community, and hybrid programs) have adopted different learning modalities to preserve a high quality of educational training. There is minimal data on specific program adaptations, related change perspectives, and program type stratification. This study sought to examine trends in curriculum changes in accredited psychiatry residency programs in the United States. METHODS: Program directors of accredited general psychiatry programs in the United States were surveyed to assess both general program details and changes in educational content, delivery, and perspectives with regard to program curricula. RESULTS: A total of 63 program directors out of 264 eligible programs completed the questionnaire (23.9%). There was a significant shift to integrate virtual learning post-pandemic (98.5%) compared to pre-pandemic (3%). However, there was no association between these modality changes and program type (p = 0.13). Furthermore, changes were noted with respect to didactic content (60%), decreased rotation sites (38%), and increased telemedicine exposure (84%) with no change of wellness days (67%) or protected time (97%). Again, the above changes had no association with program type. Use of virtual educational platforms was described as positive (59.7%) with 9 programs noting a future transition to a hybrid learning model for didactics and grand rounds. CONCLUSIONS: The findings suggest that pandemic-related curriculum adaptations occurred in all different types of psychiatry residencies and suggest a national trend to continue virtual educational platforms with regard to psychiatry didactics. However, future investigation of effectiveness of virtual learning programs in psychiatry residencies is warranted.