Drug safety in older patients with alcohol use disorder: a retrospective cohort study.

Background: Older patients with alcohol use disorder are at particular risk of developing adverse drug reactions due to multimorbidity, polypharmacy, and altered organ function. Objectives: In this study, we investigated the frequency and characteristics of potentially serious alcohol-medication interactions, potentially inappropriate medications (PIMs) for older adults, and potential drug-drug interactions (pDDIs) in a population of older patients with alcohol use disorder over a 10-year period. Design: Retrospective monocentric cohort study. Methods: Prescribed medications were screened for potentially serious alcohol-medication interactions, PIMs, and pDDIs using the POSAMINO (POtentially Serious Alcohol-Medication INteractions in Older adults) criteria, the PRISCUS 2.0 list, the FORTA (Fit fOR The Aged) classification, and the drug interaction program AiDKlinik®. Results: We enrolled 114 patients aged ⩾65 years with alcohol use disorder, who were treated in an addiction unit of a university hospital in Germany. About 80.7% of the study population had at least one potentially serious alcohol-medication interaction. Potentially serious alcohol-medication interactions most commonly affected the cardiovascular (57.7%) and the central nervous system (32.3%). A total of 71.1% of the study population received at least one prescription of a FORTA C or D drug, compared with 42.1% who received at least one PIM prescription according to the PRISCUS 2.0 list. A total of 113 moderate and 72 severe pDDIs were identified in the study population. Conclusion: Older patients with alcohol use disorders are frequently exposed to potentially serious alcohol-medication interactions, PIMs, and pDDIs. Improvements in the quality of prescribing should primarily target the use of cardiovascular and psychotropic drugs.

Methylation of the Oxytocin, Oxytocin Receptor, and Vasopressin Gene Promoters in Tobacco Use Disorder during Cessation.

INTRODUCTION: Vasopressin (AVP) and oxytocin (OT) exert sex-specific effects on social pair bonding and stress reactions while also influencing craving in substance use disorders. In this regard, intranasal oxytocin (OT) and AVP antagonists present potential treatments for tobacco use disorder (TUD). Since transcription of both hormones is also regulated by gene methylation, we hypothesized sex-specific changes in methylation levels of the AVP, OT, and OT receptor (OXTR) gene during nicotine withdrawal. METHODS: The study population consisted of 49 smokers (29 males, 20 females) and 51 healthy non-smokers (25 males, 26 females). Blood was drawn at day 1, day 7, and day 14 of smoking cessation. Craving was assessed with the questionnaire on smoking urges (QSU). RESULTS: Throughout cessation, mean methylation of the OT promoter gene increased in males and decreased in females. OXTR receptor methylation decreased in females, while in males it was significantly lower at day 7. Regarding the AVP promoter, mean methylation increased in males while there were no changes in females. Using mixed linear modeling, CpG position, time point, sex, and the interaction of time point and sex as well as time point, sex, and QSU had a significant fixed effect on OT and AVP gene methylation. The interaction effect suggests that sex, time point, and QSU are interrelated, meaning that, depending on the sex, methylation could be different at different time points and vice versa. There was no significant effect of QSU on mean OXTR methylation. DISCUSSION: We identified differences at specific CpGs between controls and smokers in OT and AVP and in overall methylation of the AVP gene. Furthermore, we found sex-specific changes in mean methylation levels of the mentioned genes throughout smoking cessation, underlining the relevance of sex in the OT and vasopressin system. This is the first study on epigenetic regulation of the OT promoter in TUD. Our results have implications for research on the utility of the AVP and OT system for treating substance craving. Future studies on both targets need to analyze their effect in the context of sex, social factors, and gene regulation.

Bifrontal electroconvulsive therapy leads to improvement of cerebral glucose hypometabolism in frontotemporal dementia with comorbid psychotic depression - a case report.

BACKGROUND: Differentiating depression and dementia in elderly patients represents a major clinical challenge for psychiatrists. Pharmacological and non-pharmacological treatment options for both conditions are often used cautiously due to fear of adverse effects. If a clinically indicated therapy is not initiated due to fear of adverse effects, the quality of life of affected patients may significantly be reduced. CASE PRESENTATION: Here, we describe the case of a 65-year-old woman who presented to the department of psychiatry of a university hospital with depressed mood, pronounced anxiety, and nihilistic thoughts. While several pharmacological treatments remained without clinical response, further behavioral observation in conjunction with 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed the diagnosis of frontotemporal dementia (FTD). To counter the pharmacological treatment resistance of psychotic depression, we decided to perform electroconvulsive therapy (ECT). Remarkably, ten sessions of ECT yielded an almost complete remission of depressive symptoms. In addition, the patient's delusional ideas disappeared. A follow-up 18F-FDG PET/CT after the ECT series still showed a frontally and parieto-temporally accentuated hypometabolism, albeit with a clear regression compared to the previous image. The follow-up 18F-FDG PET/CT thus corroborated the diagnosis of FTD, while on the other hand it demonstrated the success of ECT. CONCLUSIONS: In this case, ECT was a beneficial treatment option for depressive symptoms in FTD. Also, 18F-FDG PET/CT should be discussed as a valuable tool in differentiating depression and dementia and as an indicator of treatment response.

Potentially inappropriate medications according to PRISCUS list and FORTA (Fit fOR The Aged) classification in geriatric psychiatry: a cross-sectional study.

Adverse drug reactions (ADRs) constitute a frequent cause of hospitalization in older people. The risk of ADRs is increased by the prescription of potentially inappropriate medications for older people (PIMs). The PRISCUS list and the FORTA classification represent established tools to detect PIMs. The aim of the present study was to examine the prevalence and characteristics of PIM prescriptions on the gerontopsychiatric ward of a university hospital in Germany. To this aim, medication charts of 92 patients (mean age 75.9 ± 7.7 years; 66.3% female) were analyzed on a weekly basis until patient discharge by utilization of the PRISCUS list and the FORTA classification. Overall, 335 medication reviews comprising 2363 drug prescriptions were analyzed. 3.0% of the prescribed drugs were PIMs according to the PRISCUS list, with benzodiazepines and Z-drugs accounting for nearly half (49.3%) of all PIM prescriptions. 30.4% of the patients were prescribed at least one PRISCUS-PIM, while 43.5% of the study population took at least one FORTA class D drug. A considerable proportion of gerontopsychiatric patients were affected by PIMs; however, the overall number of PIM prescriptions in the study population was low. Further improvements in the quality of prescribing should target the use of sedating agents such as benzodiazepines and Z-drugs. Physicians should be aware of discrepancies between the PRISCUS list and the FORTA classification.

Dysregulated Methylation Patterns in Exon IV of the Brain-Derived Neurotrophic Factor (BDNF) Gene in Nicotine Dependence and Changes in BDNF Plasma Levels During Smoking Cessation.

Introduction: Several studies reported dysregulated protein levels of brain-derived neurotrophic factor (BDNF) in smokers and during cessation. However, the epigenetic regulation of the BDNF gene has not yet been investigated. We measured the plasma levels of BDNF and the epigenetic regulation of exon IV of the BDNF gene in smokers compared to healthy controls over a cessation period of 14 days. Method: We measured BDNF plasma levels and BDNF promoter methylation in 49 smokers and 51 non-smokers at baseline, day 7, and day 14 of smoking cessation. Mean methylation levels of 11 Cytosine Guanosine dinucleotides of exon IV of the BDNF gene were determined via bisulfite sequencing. Results: BDNF plasma and methylation levels were significantly lower in healthy controls when compared with smokers across all time points. BDNF levels for smokers decreased significantly during the cessation period. Comparing the sexes, female smokers showed significantly lower plasma BDNF levels than healthy controls at baseline and over 14 days of cessation. Male and female smokers showed significantly higher mean methylation rates than non-smokers at baseline. In male smokers, mean methylation levels decreased significantly during the cessation period. Conclusion: Our findings replicate the findings of previous studies that BDNF plasma levels are altered in smokers. Furthermore, BDNF expression and gene methylation are altered during the first 14 days of cessation. Our novel findings of dysregulated methylation patterns in exon IV of the BDNF gene further support the thesis that BDNF plays a role in nicotine dependence.

Differences in the promoter methylation of atrial natriuretic peptide and vasopressin in alcohol use disorder. A longitudinal case-control-study during withdrawal therapy.

BACKGROUND: Both atrial natriuretic peptide (ANP) and vasopressin (VP) influence alcohol intake and withdrawal as well as craving and are also regulated by epigenetic factors. Disturbances in expression and promoter methylation status have been described in patients suffering from alcohol use disorder and alcohol withdrawal therapy. OBJECTIVES: In this study, we wanted to map the progression of cytosine-phosphatidyl-guanine (CpG) methylation of the respective gene promoter of ANP and VP immediately after starting alcohol withdrawal therapy when compared with healthy controls METHODS: We recruited 34 males suffering from alcohol addiction or harmful use alongside 43 healthy male controls. Blood samples for methylation analyses were drawn on days 1, 2, 3, 4, and 7-10. RESULTS: There was no difference in mean methylation for both VP and ANP during withdrawal. There was no difference at the ANP CpG-sites after correction for multiple testing. Regarding VP, methylation was significantly higher at CpG 033, CpG 064, CpG 103, CpG 118, and CpG 194 and significantly lower at CpG 053, CpG 060, and CpG 214 when compared to healthy controls. Via in silico analysis, we identified transcription factor binding sites that could potentially influence methylation-dependent gene transcription. CONCLUSIONS: While there was no change in methylation status during withdrawal, significant differences in average methylation of specific CpG sites were observed for VP. We also identified the role of transcription factors in the context of promoter methylation as one potential mechanism that could explain the differences in VP levels between alcohol-dependent patients and healthy controls.

5-Aminolevulinic Acid Multispectral Imaging for the Fluorescence-Guided Resection of Brain Tumors: A Prospective Observational Study.

Fluorescence-guided surgery with five-aminolevulinic acid (5-ALA) is the state-of-the-art treatment of high-grade gliomas. However, intraoperative visualization of 5-ALA under blue light remains challenging, especially when blood covers the surgical field and thereby fluorescence. To overcome this problem and combine the brightness of visible light with the information delivered with fluorescence, we implemented multispectral fluorescence (MFL) in a surgical microscope, a technique that is able to project both information in real-time. We prospectively examined 25 patients with brain tumors. One patient was operated on two different lesions in the same setting. The tumors comprised: six glioblastomas, four anaplastic astrocytomas, one anaplastic oligodendroglioma, two meningiomas, 11 metastatic tumors, one acoustic neuroma, and one ependymoma. The MFL technique with a real-time overlay of fluorescence and white light was compared intraoperatively to the classic blue filter. All lesions were clearly visible and highlighted from the surrounding tissue. The pseudocolor we chose was green, representing fluorescence, with the surrounding brain tissue remaining in its original color. When blood was covering the surgical field, orientation was easy to maintain. The MFL technique opens the way for precise and clear visualization of fluorescence in real-time under white light. It can be easily used for the resection of all tumors accumulating 5-ALA. Drawbacks of classic PpIX fluorescence such as hidden fluorescence, intraoperative changes could be overcome with the presence of additional white light in MFL technique.