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Background: Alcohol use disorder is a major societal and individual burden that exacerbates health outcomes, decreases quality of life, and negatively affects U.S. healthcare spending. Although pharmacological treatments are available for alcohol use disorder, many of them are limited by small effect sizes and used infrequently. Citicoline is a widely available over‐the‐counter supplement with a favorable side effect profile. It acts through cholinergic pathways and phospholipid metabolism. The current report examines the effect of oral citicoline on alcohol use, craving, depressive symptoms, and cognitive outcomes in individuals with alcohol use disorder. Methods: A 12‐week, randomized, double‐blind, parallel‐group, placebo‐controlled, pilot study of citicoline (titrated to 2,000 mg/d) in 62 adults (age 18 to 75) with alcohol use disorder was conducted. Alcohol use, such as number of drinking days, amount used, and number of heavy drinking days, was assessed using the Timeline Followback method and liver enzymes, while alcohol craving was measured using the Penn Alcohol Craving Scale. A neurocognitive battery (e.g., Rey Auditory Verbal Learning Test) and depressive symptoms scale (e.g., Inventory of Depressive Symptomatology Self‐Report) scores were also collected. Data were analyzed using a random regression analysis. Results: The primary outcome analysis was conducted in the intent‐to‐treat sample and consisted of 55 participants (78.2% men and 21.8% women, mean age of 46.47 ± 9.15 years). In the assessment period, the drinking days, on average, represented 77% of the assessed days. Significant between‐group differences were not observed on alcohol use, craving, and cognitive or depressive symptom measures. Citicoline was well tolerated. Conclusions: This proof‐of‐concept study observed that citicoline was well tolerated, but was not associated with a reduction in alcohol use or other outcomes, as compared to placebo. The favorable effects reported with citicoline for cocaine use, cognitive disorders, and other conditions do not appear to extend to alcohol use disorder. [ABSTRACT FROM AUTHOR]

Background: The effects of the glucocorticoid and progesterone receptor agonist megestrol on declarative memory, and the ability of phenytoin to block these effects, were assessed. Methods: Healthy volunteers received each medication combination (placebo and megestrol, phenytoin and megestrol, and placebo and placebo) using a randomized, crossover design. The Rey Auditory Verbal Learning Test assessed declarative memory. Results: Megestrol was associated with a significant reduction in declarative memory (p = 0.0008), which was attenuated by phenytoin, and was associated with significant cortisol suppression compared to placebo (p < 0.001). Conclusion: Changes in memory and cortisol suppression were found in healthy volunteers given megestrol. [ABSTRACT FROM AUTHOR]

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In animal models, corticosterone elevations are associated with hippocampal changes that can be prevented with phenytoin. In humans, Cushing's syndrome and long-term prescription corticosteroid use are associated with a reduction in the hippocampal volume. However, little is known about the effects of short-term corticosteroid administration on the hippocampus. The current report examines changes in the hippocampal volume during a brief hydrocortisone exposure and whether volumetric changes can be blocked by phenytoin. A randomized, double-blind, placebo-controlled, within-subject crossover study was conducted in healthy adults (n=17). Participants received hydrocortisone (160 mg/day)/placebo, phenytoin/placebo, both medications together, or placebo/placebo, with 21-day washouts between the conditions. Structural MRI scans and cortisol levels were obtained following each medication condition. No significant difference in the total brain volume was observed with hydrocortisone. However, hydrocortisone was associated with a significant 1.69% reduction in the total hippocampal volume compared with placebo. Phenytoin blocked the volume reduction associated with hydrocortisone. Reduction in hippocampal volume correlated with the change in cortisol levels (r=−0.58, P=0.03). To our knowledge, this is the first report of structural hippocampal changes with brief corticosteroid exposure. The correlation between the change in hippocampal volume and cortisol level suggests that the volume changes are related to cortisol elevation. Although the findings from this pilot study need replication, they suggest that the reductions in hippocampal volume occur even during brief exposure to corticosteroids, and that hippocampal changes can, as in animal models, be blocked by phenytoin. The results may have implications both for understanding the response of the hippocampus to stress as well as for patients receiving prescription corticosteroids. [ABSTRACT FROM AUTHOR]

Depression in bipolar disorder (BPD) is challenging to treat. Therefore, additional medication options are needed. In the current report, the effect of the neurosteroid pregnenolone on depressive symptoms in BPD was examined. Adults (n=80) with BPD, depressed mood state, were randomized to pregnenolone (titrated to 500 mg/day) or placebo, as add-on therapy, for 12 weeks. Outcome measures included the 17-item Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology-Self-Report (IDS-SR), Hamilton Rating Scale for Anxiety (HRSA), and Young Mania Rating Scale (YMRS). Serum neurosteroid levels were assessed at baseline and week 12. Data were analyzed using a mixed model ANCOVA with a between factor of treatment assignment, a within factor (repeated) of visit, and the baseline value, as well as age and gender, as covariates. In participants with at least one postbaseline visit (n=73), a significant treatment by week interaction for the HRSD (F(5,288)=2.61, p=0.025), but not IDS-SR, was observed. Depression remission rates were greater in the pregnenolone group (61%) compared with the placebo group (37%), as assessed by the IDS-SR (χ2(1)=3.99, p=0.046), but not the HRSD. Large baseline-to-exit changes in neurosteroid levels were observed in the pregnenolone group but not in the placebo group. In the pregnenolone group, baseline-to-exit change in the HRSA correlated negatively with changes in allopregnanolone (r(22)=−0.43, p=0.036) and pregNANolone (r(22)=−0.48, p=0.019) levels. Pregnenolone was well tolerated. The results suggest that pregnenolone may improve depressive symptoms in patients with BPD and can be safely administered. [ABSTRACT FROM AUTHOR]

Background: In animal models, corticosteroids are associated with changes in hippocampal structure and functioning that are prevented by glutamate release inhibitors or N-methyl-D-aspartate (NMDA) receptor antagonists. Cushing''s disease and prescription corticosteroid administration are also associated with memory impairment and hippocampal atrophy. Use of NMDA receptor antagonists to attenuate corticosteroid effects in humans has not been investigated. We examine the NMDA receptor antagonist memantine in patients receiving corticosteroids. Methods: Twenty outpatients receiving long-term oral corticosteroid therapy were randomized to 8 weeks of memantine (maximum dose 20 mg/day) and 8 weeks of placebo in a double-blind fashion, with a 4-week washout period between courses. Declarative memory was assessed with the Hopkins Verbal Learning Test (HVLT) and mood with the Hamilton Rating Scale for Depression and Young Mania Rating Scale. Changes in outcome measures were compared during memantine and placebo exposure. Results: Seventeen participants completed both treatment phases and were used in the analysis. Significant improvement (p < .05) in total and delayed recall on the HVLT was observed with memantine as compared with placebo. No significant changes in mood were observed. Conclusions: Memantine therapy was associated with improvement in declarative memory but not mood in patients receiving prescription corticosteroids. [Copyright &y& Elsevier]

Considering the escalating gap between the population-level need for substance use services and the availability of board-certified addiction specialty physicians, all psychiatrists must be equipped to treat substance use disorders. Residency training programs must therefore ensure that graduates are equipped with a sufficient knowledge base and skill set to treat substance use disorders, including an understanding of medications for addiction treatment and appropriate selection and utilization of psychotherapy for substance use disorders. Resources for teaching psychiatric residents about psychotherapeutic approaches to substance use disorders are often limited, and many programs may struggle to include this content in their curricula. The authors highlight the core evidence-based psychotherapeutic approaches relevant to the care of patients with substance use disorders and identify supervised experiential learning opportunities for psychiatric residents to practice psychotherapy for substance use disorders during existing clinical rotations within their general psychiatry residency programs., Competing Interests: The authors report no financial relationships with commercial interests.