Novel paradigms for the gut-brain axis during alcohol withdrawal, withdrawal-associated depression, and craving in patients with alcohol use disorder.

Introduction: Patients with alcohol use disorder (AUD) exhibit symptoms such as alcohol withdrawal, depression, and cravings. The gut-immune response may play a significant role in manifesting these specific symptoms associated with AUD. This study examined the role of gut dysfunction, proinflammatory cytokines, and hormones in characterizing AUD symptoms. Methods: Forty-eight AUD patients [men (n = 34) and women (n = 14)] aged 23-63 years were grouped using the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA) as clinically significant (CS-CIWA [score > 10] [n = 22]) and a clinically not-significant group (NCS-CIWA [score ≤ 10] [n = 26]). Clinical data (CIWA, 90-day timeline followback [TLFB90], and lifetime drinking history [LTDH]) and blood samples (for testing proinflammatory cytokines, hormones, and markers of intestinal permeability) were analyzed. A subset of 16 AUD patients was assessed upon admission for their craving tendencies related to drug-seeking behavior using the Penn-Alcohol Craving Score (PACS). Results: CS-CIWA group patients exhibited unique and significantly higher levels of adiponectin and interleukin (IL)-6 compared to NCS-CIWA. In the CS group, there were significant and high effects of association for the withdrawal score with gut-immune markers (lipopolysaccharide [LPS], adiponectin, IL-6, and IL-8) and for withdrawal-associated depression with gut-immune markers (scored using MADRS with LPS, soluble cells of differentiation type 14 [sCD14], IL-6, and IL-8). Craving (assessed by PACS, the Penn-Alcohol Craving Scale) was significantly characterized by what could be described as gut dysregulation (LBP [lipopolysaccharide binding protein] and leptin) and candidate proinflammatory (IL-1ß and TNF-α) markers. Such a pathway model describes the heavy drinking phenotype, HDD90 (heavy drinking days past 90 days), with even higher effects (R2 = 0.955, p = 0.006) in the AUD patients, who had higher ratings for cravings (PACS > 5). Discussion: The interaction of gut dysfunction cytokines involved in both inflammation and mediating activity constitutes a novel pathophysiological gut-brain axis for withdrawal symptoms and withdrawal-associated depression and craving symptoms in AUD. AUD patients with reported cravings show a significant characterization of the gut-brain axis response to heavy drinking. Trial registration: ClinicalTrials.gov, identifier: NCT# 00106106.

Psychotropic Medication Adherence in Children and Adolescents.

Researchers believe that almost 20% of children and adolescents struggle with chronic and persistent mental health concerns. Mental health is the leading cause of disability in the United States. Youth can struggle with several impairing mental health disorders, such as attention-deficit/hyperactivity disorder, mood disorders, psychotic disorders, and autism spectrum disorder. Inadequately treated chronic mental illnesses can adversely affect the growing brain profoundly, including academic decline, early school dropout, cognitive deficits, interpersonal relationship concerns, aggression, suicide attempts or completion, substance use disorders, frequent hospital admissions, and inability to maintain employment. Even if diagnosed early in their course of illness, many of these individuals struggle to continue medications as prescribed. The factors predicting adherence to medications are underresearched in children and adolescents. Psychotropic medication compliance is a complicated issue that is tied to various aspects of caring for a minor individual. Hence, it is relevant to discuss factors that are predicted to contribute to noncompliance in this age group. The purpose of this review is to carefully consider the gaps in knowledge, suggesting interventions by using established instruments and clinical strategies to resolve the identified barriers for improving medication adherence. Compliance should be targeted at various levels, including the entire family tree and the treatment team.

Dilemma of Treating Psychosis Secondary to Stroke.

Post-stroke psychosis is prevalent and disabling with increased mortality risk. Treatment for post-stroke psychosis is limited in this staggering medical concern. The most commonly used medications are antipsychotics, however, the risk for stroke increases further with the use of antipsychotics. Furthermore, interventional clinical studies have not been carried out to test the efficacy and safety of antipsychotics in the management of post-stroke psychosis. We present a case of post-stroke psychosis to highlight the risks faced by these patients in terms of daily function and safety concerns and the challenges encountered in treatment due to poor response to the conventional antipsychotics; and so calling attention to early diagnosis and improved treatment options. More clinical investigations are needed to address the pathology associated with the clinical presentation and exploring the pharmacotherapies to improve efficacy and safety of treatment for post-stroke psychosis.

Measuring the Effectiveness of Benzodiazepine Prescriptions Control in Community Setting Using Prescription Drug Monitoring Program (PDMP).

Benzodiazepines have been widely prescribed for several years for the treatment of anxiety, insomnia, and post-traumatic stress disorder (PTSD). Benzodiazepines were meant to be for short term use but in clinical settings long term use has been the "norm" for the treatment. Benzodiazepines are known for addiction potential and have been involved in accidental overdose deaths. According to the National Institute on Drug Abuse (NIDA), there has been a tenfold increase in the number of deaths due to overdose from 1999 to 2017. Benzodiazepines contributed to staggering high figures of 11,537 deaths in 2017 alone. Kentucky was ranked 4th in overdose related deaths in 2015 by CDC. Seeing this rise in overdose deaths, our community mental health clinics (CMHC) took the initiative to protect the community by removing benzodiazepines from the approved formulary in all adult outpatient community mental health clinics (total six clinics) in 2016. This project was initiated to protect the community from overdose deaths. In order to see the decrease in the benzodiazepine prescriptions, we did a quarterly Kentucky All Schedule Prescription Electronic Reporting (KASPER) prescriber's reports to see the trend. The goal of this project was to monitor the trend of benzodiazepine prescription control in CMHC. Our hypothesis was implementation of CMHC "No Benzodiazepine" policy would decrease in the number of prescriptions. To implement this change, we made a committee to educate staff including physicians, APRN's and therapists. Patients were also educated and informed regarding benzodiazepine free policy. Education materials were posted in the clinics and handed over to patients. Patients were offered individual and group therapy sessions to learn coping skills to cope with their anxiety. Patients had the option of inpatient detoxification, if clinically indicated. No new patients were started on benzodiazepines and patients who were already on benzodiazepines were slowly titrated off. Slow titration over the course of a few months was done as needed and tolerated. Quarterly, prescriber's prescription reports were generated with the help of KASPER (KASPER is PDMP in the state of Kentucky). After analyzing quarterly reports over the span of 2 years, we concluded that there was a total of 89% decrease in benzodiazepine prescriptions. We are hoping to reach close to 100% in the next few years. We conduct a Mental Health Statistics Improvement Program (MHSIP) which is a general patient satisfaction survey done annually. We used this data to monitor the change with this new policy. Open patients report was run to monitor any change in case load before and after the implementation of the policy. After compilation of the KASPER/ PDMP data of all the prescribers- MD's and APRN's, we found an 89% decrease in the number of benzodiazepines prescriptions over the span of 2 years. We did the open patients report and did not find any decrease in case load. In 2016, there were 10,359 open patients and in 2018 there were 12,266 open patients. We reviewed the MHSIP general patient satisfaction survey that is done annually, and we did not find any major difference in overall satisfaction as compared to previous years. These practice- based interventions implementing harm reduction strategies suggest that, although it was a difficult task, with strict adherence to no benzodiazepine policy, we were able to achieve a stark drop in the number of benzodiazepine prescriptions, in the span of 2 years, and have been able to continue to maintain the low numbers of benzodiazepine prescriptions.

Dysregulation in Plasma ω3 Fatty Acids Concentration and Serum Zinc in Heavy Alcohol-Drinking HCV Patients.

Alcohol use disorder (AUD) patients comorbid with hepatitis C virus (HCV) infection (HCV + AUD) could have progressively severe clinical sequels of liver injury and inflammation. Serum zinc and several polyunsaturated fatty acids (PUFAs) get dysregulated in AUD as well as HCV. However, the extent of dysregulation of PUFAs and zinc deficiency and their interaction in HCV + AUD as a comorbid pathology has not been studied. We examined the role of dysregulation of FAs and low zinc in HCV + AUD patients. 138 male and female participants aged 21-67 years were grouped as HCV-only (Gr. 1; n = 13), HCV + AUD (Gr. 2; n = 25), AUD without liver injury (Gr. 3; n = 37), AUD with liver injury (Gr. 4; n = 51), and healthy volunteers (Gr. 5 or HV; n = 12). Drinking history, individual demographic measures, fasting fatty acids, liver function, and zinc were measured and analyzed. HCV + AUD patients showed the highest ALT level compared to the rest of the groups. Serum zinc concentrations were the lowest, and the proinflammatory shift was the highest (characterized by ω6 : ω3 ratio) in the HCV + AUD patients. Total ω3, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA5,3) were the lowest in HCV + AUD patients. Total ω3, α-linoleic acid (α-LA) along with covariable number of drinking days past 90 days (NDD90), eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA5,3) independently showed significant association with low zinc in the HCV + AUD patients. Heavy drinking pattern showed that NDD90 has a significant mediating role in the representation of the relationship between candidate ω3 PUFAs and zinc uniquely in the HCV + AUD patients. Low serum zinc showed a distinctively stronger association with total and candidate ω3s in the HCV + AUD patients compared to the patients with HCV or AUD alone, supporting dual mechanism involved in the exacerbation of the proinflammatory response in this comorbid cohort. This trial is registered with NCT#00001673.