Effect of a high dose atorvastatin as added-on therapy on symptoms and serum AMPK/NLRP3 inflammasome and IL-6/STAT3 axes in patients with major depressive disorder: randomized controlled clinical study.

Background: Neuroinflammation pathways have been associated with the development of major depressive disorders (MDD). The anti-inflammatory characteristics of statins have been demonstrated to have significance in the pathophysiology of depression. Aim: To investigate the mechanistic pathways of high dose atorvastatin in MDD. Patients and methods: This trial included 60 patients with MDD who met the eligibility requirements. Two groups of patients (n = 30) were recruited by selecting patients from the Psychiatry Department. Group 1 received 20 mg of fluoxetine plus a placebo once daily. Group 2 received fluoxetine and atorvastatin (80 mg) once daily. All patients were assessed by a psychiatrist using the Hamilton Depression Rating Scale (HDRS). A HDRS score of ≤7 indicates remission or partial remission [HDRS<17 and>7]. Response was defined as ≥ 50% drop in the HDRS score. The serum concentrations of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP-3), interleukin-6 (IL-6), adenosine monophosphate activated protein kinase (AMPK), and signal transducer and activator of transcription factor-3 (STAT-3) were measured. Results: The atorvastatin group showed a significant reduction in the levels of all measured markers along with a statistical increase in the levels of AMPK when compared to the fluoxetine group. The atorvastatin group displayed a significant decrease in HDRS when compared to its baseline and the fluoxetine group. The response rate and partial remission were higher in the atorvastatin group than fluoxetine (p = 0.03, and p = 0.005), respectively. Conclusion: These results imply that atorvastatin at high doses may be a promising adjuvant therapy for MDD patients by altering the signaling pathways for AMPK/NLRP3 and IL-6/STAT-3. Clinical Trial Registration: clinicaltrials.gov, identifier NCT05792540.

Suicidality among university students in the Eastern Mediterranean region: A systematic review.

The prevalence of suicide attempts and suicidal ideation among university students is a global concern. Cultural values, social determinants, religion, and especially growing stress all play an important role in this. This systematic review aimed to identify potential protective and risk factors thought to be associated with suicidal ideation among students in the Eastern Mediterranean region and highlight the importance of developing an effective health care response. MEDLINE, CINAHL, Embase, PsycINFO, WHO Global Health Library, IMEMR, Web of Science Core Collections and Farsi and Arabic databases were searched for papers in English, Farsi, and Arabic. A combination of validated filters, free text keywords, and Mesh and Non-Mesh terms were used to retrieve relevant literature. A total of 2774 papers were found after the search, 257 selected for full-text review, and 72 papers included in the final review. Family and peer support play a potential protective role in the development of suicidal ideation among university students, while adverse life events, bullying, depression, anxiety, and other mental health conditions were identified as risk factors. Suicidality was likely under-reported due to stigma around social and cultural factors. Factors involving religion and culture may act as both protective and risk factors and require more in-depth investigation. The student population in the Eastern Mediterranean region face many challenges. The common theme of suicidality emerged as an indicator of an imbalance of resources and stress, which needs to be addressed proactively, given a most likely underreporting of suicidal ideation and attempts due to stigma.

Treatment approaches and outcome trajectories for youth with high-risk opioid use: A narrative review.

AIM: First use of opioids often happens in adolescence and an increasing number of opioid overdoses are being reported among youth. The purpose of this narrative review was to present the treatment approaches for youth with high-risk opioid use, determine whether the literature supports the use of opioid agonist treatment among youth and identify evidence for better treatment outcomes in the younger population. METHODS: A search of the literature on PubMed using MeSH terms specific to youth, opioid use and treatment approaches generated 1436 references. Following a screening process, 137 papers were found to be relevant to the treatment of high-risk opioid use among youth. After full-text review, 19 eligible studies were included: four randomized controlled trials, nine observational studies and six reviews. RESULTS: Research for the different treatment options among youth is limited. The available evidence shows better outcomes in terms of retention in care and cost-effectiveness for opioid agonist treatment than abstinence-based comparisons. Integrating psychosocial interventions into the continuum of care for youth can be an effective way of addressing comorbid psychiatric conditions and emotional drivers of substance use, leading to improved treatment trajectories. CONCLUSIONS: From the limited findings, there is no evidence to deny youth with high-risk opioid use the same treatment options available to adults. A combination of pharmacological and youth-specific psychosocial interventions is required to maximize retention and survival. There is an urgent need for more research to inform clinical strategies toward appropriate treatment goals for such vulnerable individuals.

Mental health outcomes and help-seeking behaviours among Egyptian medical students: A cross-sectional study.

AIM: Approximately half of the population in Egypt is under the age of 25. Globally, mental illness represents the highest burden of disease in this age group. Yet in Egypt, there is still no youth-specific mental health system in place and the vast majority of young people do not have access to any professional mental health support. The objective of this study was to describe the mental health needs of Egyptian youth and the resources they use when seeking help. METHODS: An online cross-sectional survey was distributed among medical students at Tanta University in Egypt. Of the 707 individuals who completed the survey (90.9% response rate), 60.5% were female, 62.0% lived in urban and suburban areas, and the mean age of the sample was 20.5 (±1.8) years old. RESULTS: More than half (54%) of the students reported that they had been affected by mental health problems at some point in their lives. Anxiety and depression were the most common problems. Regarding help-seeking behaviours, participants mainly searched the web or spoke to peers and relatives; few reported approaching medical professionals. The majority of participants (59.7%) reported being disappointed with the current mental health care system in Egypt. CONCLUSIONS: There is a high prevalence of mental challenges among Egyptian youth and the health care system is not adequately prepared to respond to their needs. E-Mental Health and online interventions seem to be a promising solution that could increase access to mental health services for Egyptian youth.

Impact of opioid agonist treatment on mental health in patients with opioid use disorder: a systematic review and network meta-analysis of randomized clinical trials.

Background: There is a knowledge gap in systematic reviews on the impact of opioid agonist treatments on mental health.Objectives: We compared mental health outcomes between different opioid agonist treatments and placebo/waitlist, and between the different opioids themselves.Methods: This meta-analysis of randomized clinical trials (RCTs) was pre-registered at PROSPERO (CRD42018109375). Embase, MEDLINE, PsychInfo, CINAHL Complete, and Web of Science Core Collection were searched from inception to May 2020. RCTs were included if they compared opioid agonists with each other or with placebo/waitlist in the treatment of patients with opioid use disorder and reported at least one mental health outcome after 1-month post-baseline. Studies with psychiatric care, adjunct psychotropic medications, or unbalanced psychosocial services were excluded. The primary outcome was overall mental health symptomatology, e.g. Symptom Checklist 90 total score, between opioids and placebo/waitlist. Random effects models were used for all the meta-analyses.Results: Nineteen studies were included in the narrative synthesis and 15 in the quantitative synthesis. Hydromorphone, diacetylmorphine (DAM), methadone, slow-release oral morphine, buprenorphine, and placebo/waitlist were among the included interventions. Based on the network meta-analysis for primary outcomes, buprenorphine (SMD (CI95%) = -0.61 (-1.20, -0.11)), DAM (-1.40 (-2.70, -0.23)), and methadone (-1.20 (-2.30, -0.11)) were superior to waitlist/placebo on overall mental health. Further direct pairwise meta-analysis indicated that overall mental health improved more in DAM compared to methadone (-0.23 (-0.34, -0.13)).Conclusions: Opioid agonist treatments used for the treatment of opioid use disorder improve mental health independent of psychosocial services.

Understanding eHealth Cognitive Behavioral Therapy Targeting Substance Use: Realist Review.

BACKGROUND: There is a growing body of evidence regarding eHealth interventions that target substance use disorders. Development and funding decisions in this area have been challenging, due to a lack of understanding of what parts of an intervention work in which context. OBJECTIVE: We conducted a realist review of the literature on electronic cognitive behavioral therapy (eCBT) programs for substance use with the goal of answering the following realist question: "How do different eCBT interventions for substance use interact with different contexts to produce certain outcomes?" METHODS: A literature search of published and gray literature on eHealth programs targeting substance use was conducted. After data extraction, in order to conduct a feasible realist review in a timely manner, the scope had to be refined further and, ultimately, only included literature focusing on eCBT programs targeting substance use. We synthesized the available evidence from the literature into Context-Mechanism-Outcome configurations (CMOcs) in order to better understand when and how programs work. RESULTS: A total of 54 papers reporting on 24 programs were reviewed. Our final results identified eight CMOcs from five unique programs that met criteria for relevance and rigor. CONCLUSIONS: Five strategies that may be applied to future eCBT programs for substance use are discussed; these strategies may contribute to a better understanding of mechanisms and, ultimately, may help design more effective solutions in the future. Future research on eCBT programs should try to understand the mechanisms of program strategies and how they lead to outcomes in different contexts.