Antidepressants compared to placebo for people with binge eating disorder: A systematic review and meta-analysis.

Binge eating disorder (BED) is the most prevalent eating disorder. Treatment options include pharmacotherapy as well as psychotherapy, with the latter recommended as a first-line option. However, the use of psychotherapeutic interventions poses several challenges. Antidepressants are easily accessible, but they lack robust evidence-base. This systematic review aims to comprehensively examine the efficacy and safety of antidepressants for the treatment of BED. Five databases were searched for randomized controlled trials (RCTs) comparing antidepressants vs. placebo in BED until 23/11/2023. Pairwise meta-analytic evaluations were performed. The primary outcomes were remission and binge eating frequency. Secondary outcomes were response to treatment, eating psychopathology, depression, anxiety, body weight, Body Mass Index (BMI), all-cause discontinuation, discontinuation due to adverse effects and total adverse events. Sixteen RCTs with a total of 984 participants were meta-analysed. Antidepressants were more effective than placebo in achieving remission (RR: 1.39, 95 % CI: 1.04 to 1.86) and in reducing binge eating episodes (SMD: -0.29, 95 % CI: -0.51 to -0.06). Similarly, in the secondary outcomes of response and depression, antidepressants demonstrated superiority over placebo. Antidepressants appear to be effective in reducing symptoms of BED. Small samples and effect sizes hinder the generalizability and clinical utility of these results. There is a lack of follow-up findings regarding the maintenance of effects. There is a pressing need for more RCTs examining antidepressants and other types of pharmacotherapy. Future research should include larger number of participants and increase the duration of follow-up.

Is cognitive behavioral therapy more effective than pharmacotherapy for binge spectrum disorders? A systematic review and meta-analysis.

OBJECTIVES: Binge spectrum disorders are prevalent worldwide. Psychiatric and medical comorbidities are common, and societal costs are significant. Evidence-based treatment remains underutilized. Cognitive behavioral therapy is the recommended first-line treatment, but pharmacotherapy may be easier to access. INTERVENTIONS: Meta-analytic evidence directly comparing cognitive behavioral therapy with pharmacotherapy is lacking. We aimed to compare the effects of cognitive behavioral therapy interventions with any pharmacological treatment for binge spectrum disorders. We searched PubMed, Embase, CENTRAL, ClinicalTrials.gov and reference lists for randomized controlled trials comparing cognitive behavioral therapy with any pharmacotherapy for bulimia nervosa/binge eating disorder and performed pairwise meta-analytic evaluations. PRIMARY OUTCOMES: Primary outcomes are remission and frequency of binges. Secondary outcomes are frequency of purges, response, eating disorder psychopathology, weight/body mass index, depression, anxiety, quality of life and dropouts. RESULTS: Eleven randomized controlled trials comparing cognitive behavioral therapy with fluoxetine/imipramine/desipramine/methylphenidate/sibutramine were identified (N = 531). Cognitive behavioral therapy was superior to antidepressants in terms of remission, frequency of binges and eating disorder psychopathology. There were no statistically significant differences for any of the individual cognitive behavioral therapy vs drug comparisons in terms of response/depression/anxiety/weight/quality of life/dropouts. Cognitive behavioral therapy was not superior to sibutramine/methylphenidate for the primary outcomes. CONCLUSIONS: Data are scarce, comparisons underpowered and, considering the inherent methodological limitations of psychotherapy trials, questions arise regarding the presumed superiority of cognitive behavioral therapy. Further research is needed.

Sleep disorders and Alzheimer's disease pathophysiology: The role of the Glymphatic System. A scoping review.

BACKGROUND: Alzheimer's disease (AD) is highly intertwined with sleep disturbances throughout its whole natural history. Sleep consists of a major compound of the functionality of the glymphatic system, as the synchronized slow-wave activity during NREM facilitates cerebrospinal and interstitial long-distance mixing. OBJECTIVE: The present study undertakes a scoping review of research on the involvement of the glymphatic system in AD-related sleep disturbances. DESIGN: we searched Medline, Embase, PsychInfo and HEAL-link databases, without limitations on date and language, along with reference lists of relevant reviews and all included studies. We included in vivo, in vitro and post-mortem studies examining glymphatic implications of sleep disturbances in human populations with AD spectrum pathology. A thematic synthesis of evidence based on the extracted content was applied and presented in a narrative way. RESULTS: In total, 70 original research articles were included and were grouped as following: a) Protein aggregation and toxicity, after sleep deprivation, along with its effects on sleep architecture, b) Glymphatic Sequalae in SDB, yielding potential glymphatic markers c) Circadian Dysregulation, d) Possible Interventions. CONCLUSIONS: this review sought to provide insight into the role of sleep disturbances in AD pathogenesis, in the context of the glymphatic disruption.

Effects of Antidepressants on Sleep in Post-traumatic Stress Disorder: An Overview of Reviews.

Antidepressants are a commonly used, easily accessible, and overall safe treatment option for post-traumatic stress disorder (PTSD). The present review aims to evaluate the efficacy and safety of antidepressants in treating sleep disturbances in patients with PTSD. PubMed and the Cochrane Library were searched (July 2022) for systematic reviews and meta-analyses on the treatment of PTSD. Moreover, PubMed and ClinicalTrials.gov were searched for individual trials investigating the antidepressant treatment of PTSD (up to September 2022), and reference lists of all possibly relevant identified studies were screened. Sleep-related outcomes, i.e., total sleep time, sleep quality, dreams/ nightmares, insomnia, and somnolence, were extracted independently by at least two reviewers. Metaanalytic evaluations were performed wherever possible. 39 randomised controlled trials (RCTs) were identified; data from pooled analyses, reviews, and observational studies were used for antidepressants with a weak evidence base or when their findings were deemed important. Overall, scarce data exist on the effects of antidepressants on sleep outcomes among patients with PTSD. Some evidence may support the use of amitriptyline, nefazodone, paroxetine, and sertraline for improving sleep in patients with PTSD. Τhere was a meta-analytical trend indicating improvement of nightmares with fluoxetine, less insomnia with amitriptyline and more with brofaromine, as well as more somnolence with paroxetine vs. placebo, respectively. However, data from more than 1 RCT with a considerable number of patients were only available for paroxetine. Evidence is insufficient to draw safe conclusions. More and better-designed RCTs, with consistent reporting of sleep-related outcomes, are needed.

FACTORS ASSOCIATED WITH NON-ATTENDANCE TO OUTPATIENT CONSULTATION-LIAISON PSYCHIATRY APPOINTMENTS: A RETROSPECTIVE COHORT STUDY.

BACKGROUND: Non-attendance to outpatient mental health appointments is associated with adverse clinical and financial outcomes. The aim of this study was to investigate the rates of non-attendance to outpatient Consultation-Liaison Psychiatry (CLP) appointments and the factors associated with non-attendance. SUBJECTS AND METHODS: Retrospective cohort study, including two groups of data: 950 initial and 3503 follow-up appointments between 01/01/2015 and 31/12/2019. We employed descriptive statistics, parametric/non-parametric tests and logistic regression analysis. We used a range of environmental, socio-demographic and service-related characteristics as independent parameters and non-attendance as the dependent parameter. RESULTS: Initial and follow-up non-attendance rates were 27.5% and 18.8% respectively. Opting-out text message reminders was associated with both initial and follow-up non-attendance. Higher education was associated with initial non-attendance, whereas lower education with follow-up non-attendance. Other factors associated with non-attendance to initial appointments were: English being the participant's primary communication language, having an appointment with a psychiatrist as opposed to a trained nurse or Cognitive Behavioural Therapist, and longer waiting time. Follow-up non-attendance was also associated with younger age, shorter driving distance and higher income/employment. CONCLUSION: We suggest that improving opt-in rates through a combination of staff and patient education and promotion, improving waiting lists, reducing the stigma associated with seeing a psychiatrist, but also perhaps targeting different socio-economic groups of patients with different strategies should be the focus of policy making to tackle non-attendance. Further research into patient-related and environmental factors, such as day of the week, driving distance, language of primary communication, education, income and employment is warranted in order to design more effective policies and improve engagement with CLP, but also psychiatric services in general.

Physical activity and exercise for the prevention and management of mild cognitive impairment and dementia: a collaborative international guideline.

BACKGROUND: Physical activity and exercise have been suggested as effective interventions for the prevention and management of mild cognitive impairment (MCI) and dementia, but there are no international guidelines. OBJECTIVES: To create a set of evidence- and expert consensus-based prevention and management recommendations regarding physical activity (any bodily movement produced by skeletal muscles that results in energy expenditure) and exercise (a subset of physical activity that is planned, structured, repetitive), applicable to a range of individuals from healthy older adults to those with MCI/dementia. METHODS: Guideline content was developed with input from several scientific and lay representatives' societies. A systematic search across multidisciplinary databases was carried out until October 2021. Recommendations for prevention and management were developed according to the GRADE and complemented by consensus statements from the expert panels. RECOMMENDATIONS: Physical activity may be considered for the primary prevention of dementia. In people with MCI there is continued uncertainty about the role of physical activity in slowing the conversion to dementia. Mind-body interventions have the greatest supporting evidence. In people with moderate dementia, exercise may be used for maintaining disability and cognition. All these recommendations were based on a very low/low certainty of evidence. CONCLUSIONS: Although the scientific evidence on the beneficial role of physical activity and exercise in preserving cognitive functions in subjects with normal cognition, MCI or dementia is inconclusive, this panel, composed of scientific societies and other stakeholders, recommends their implementation based on their beneficial effects on almost all facets of health.

Antimanic Efficacy, Tolerability, and Acceptability of Clonazepam: A Systematic Review and Meta-Analysis.

(1) Background: The use of benzodiazepines for the treatment of acute mania remains prevalent. This systematic review and meta-analysis provides an updated assessment of Clonazepam's antimanic efficacy, tolerability, and acceptability. (2) Methods: A systematic search of multiple databases and clinical trial registries was conducted, aiming to identify any controlled studies of Clonazepam vs. placebo or any other pharmacotherapy for the treatment of acute mania. Pairwise meta-analytic evaluations were performed. (3) Results: Six studies were included with a total number of 192 participants, all of which were randomized controlled trials. Clonazepam may be superior to a placebo in the acute phase of treatment and no different to Lithium and Haloperidol in terms of efficacy, both acutely and in the medium to long term. Clonazepam may be an acceptable and well-tolerated treatment for acute mania, especially when used as an augmentation strategy. Comparisons were underpowered, with minimal sample sizes and only one study per comparison in many cases, thus limiting the generalizability of our findings and hindering firm clinical conclusions. (4) Conclusions: Given the prevalence of benzodiazepine use in current practice, more and larger studies are urgently needed.

Pharmacotherapy compared to placebo for people with Bulimia Nervosa: A systematic review and meta-analysis.

Bulimia Nervosa is a disorder with high rates of psychiatric and medical comorbidity and substantial societal costs. Cognitive Behavioural Therapy is considered the preferred treatment, but access can be problematic. Pharmacotherapy is more accessible but remains significantly underutilised. We aimed to assess the efficacy, tolerability, and safety of all available forms of pharmacotherapy for the treatment of bulimia nervosa. We conducted a comprehensive search of PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and reference lists of relevant articles up until April 2023. The primary outcomes were remission and binge frequency. 52 randomised controlled trials (RCTs) involving 3313 participants were included in the meta-analysis. Overall, no significant difference was observed between drugs and placebo in terms of remission; however, the available data were limited. Notably, drugs, particularly antidepressants, demonstrated a significant reduction in the frequency of binge episodes compared to placebo. Antidepressants were also found to be more effective than placebo in terms of treatment response and other clinically meaningful outcomes. An important limitation is that few RCTs were available for individual drugs. Our findings provide evidence supporting the increased utilisation of pharmacotherapy in clinical practice and underscore the need for further research involving larger populations and a broader range of outcomes.

A novel conceptual framework for the functionality of the glymphatic system.

The glymphatic system is responsible for the clearance of the potentially harmful metabolic waste of the central nervous system. The prevalent theory is that the cerebrospinal fluid (CSF) circulates in the perivascular space (PVS) and through the astrocytes' aquaporin-4 channels (AQ-4), and it is then drained by the lymphatic vessels after mixing with interstitial fluid (ISF). However, there is little evidence supporting this hypothesis. A deeper understanding of the physiology of the glymphatic system could transform the way we understand neuropathology and our approach to treating neurological and neuropsychiatric disorders. In this review, we introduce a new conceptual framework for the functionality of the glymphatic system, offering new directions for future research. We propose that CSF and ISF exchange flow depends on arterial pulsation, respiration, posture, and sleep. PVS changes due to disrupted cerebral autoregulation, alternations of intrathoracic pressure, venous flow, and body position can also influence the glymphatic flow. The role of respiration remains controversial due to the variety of parameters that interfere with glymphatic functionality. Slow-wave sleep is important for glymphatic clearance due to neuronal electromagnetic synchronization and expansion of the interstitial space. Therefore, sleep and vascular disorders, as well as aging, may hinder glymphatic flow and induce a noxious milieu of susceptibility to neurodegenerative disorders because of metabolic waste accumulation. We lastly introduce a new idea postulating that electromagnetic induction may constitute one of the propelling forces for the convectional current and mixing of CSF and ISF.

Factors associated with increased suicidality risk following referral for isotretinoin commencement.

OBJECTIVE: To establish whether there is a significant change in suicidality risk following psychiatric assessment for commencement of isotretinoin and identify factors that underpin any potential risk change. METHOD: Retrospective cohort study. Suicidality risk was defined as a combination of the following: (i) actual/intended self-harm and/or attempted/completed suicide, and (ii) increased service utilisation associated with suicidal ideation/behaviour. All patients referred to Psychiatry for assessment prior to commencement of isotretinoin between 2014 and 2019 were examined. Inclusion criteria: >16 years of age, assessed for commencement of isotretinoin, complete clinical records. Data were collected by reviewing the Electronic Patient Records. Fifty-seven patients were eligible. We employed descriptive statistics, parametric/non-parametric/normality tests and logistic regression analysis, using socio-demographic and clinical characteristics as independent parameters, and suicidality risk as the dependent parameter. RESULTS: Actual/intended self-harm/attempted suicide decreased significantly following assessment without significant change in service utilisation. Female gender, absence of protective factors and assessment by Consultation-Liaison Psychiatry were linked to increased suicidality risk, after controlling for age, ethnicity, recommendation for isotretinoin, and substance misuse. CONCLUSIONS: Psychiatric assessment is helpful before commencing isotretinoin. Female gender, and absence of ongoing psychopharmacological and/or psychological intervention and/or regular psychiatric follow-up predict increased suicidality risk among patients assessed for prescription of isotretinoin.

Short-term respiratory effects of e-cigarettes in healthy individuals and smokers with asthma.

BACKGROUND AND OBJECTIVE: This study investigated the duration of immediate respiratory effects of e-cigarette smoking (ECS) and tested the hypothesis that ECS has more prominent effects in asthmatics compared with healthy smokers (HS). METHODS: Fifty-four smokers, 27 healthy (HS group) and 27 with intermittent asthma (mild asthma (MA) group) underwent a control session (no liquid, no resistor coil inside e-cigarette cartridge) and an experimental session of ECS using standardized puffing settings. Impulse oscillometry impedance (Z), resistance (R), reactance (X) and fractional exhaled nitric oxide (FeNO) were measured before and 0, 15 and 30 min after control and experimental sessions. RESULTS: Control session revealed no significant changes. In the experimental session, immediately post-ECS, both groups exhibited a significant increase in respiratory system total impedance at 5 Hz (Z5) (P < 0.001), respiratory system resistance at 5 Hz (R5) (P < 0.001), respiratory system resistance at 10 Hz (R10) (P < 0.001), respiratory system resistance at 20 Hz (R20) (P < 0.05), resonant frequency (P < 0.001) and reactance area (P < 0.05). MA exhibited higher baseline values and a more prominent effect immediately after ECS compared with HS for Z5 (P = 0.022), R5 (P = 0.010) and R10 (P = 0.013). FeNO decreased significantly in both groups (P < 0.001); HS returned to baseline values in ≤15 min while the MA maintained significantly lower values for an additional 15 min (P < 0.05) and returned to baseline values at 30 min post-ECS. CONCLUSION: A single session of ECS had respiratory mechanical and inflammatory effects, which were more prominent in smokers with asthma.

Unusual psychotic presentation after discontinuation of treatment in a patient with Wilson's disease: a case report.

Psychiatric manifestations are common in patients with Wilson's Disease(WD), and they are usually correlated with neurological symptoms. However, psychotic presentation without neurological symptoms has rarely been reported. We present a case of WD involving a 34-year-old gentleman who was diagnosed at the age of 22, but due to lack of medication for approximately 5 months was admitted in a psychiatric ward with delusional thoughts of grandeur and persecution, echopraxia and echolalia. No neurological impairment, ophthalmic manifestations or liver abnormalities were identified. Through this report, we aim to discuss the pathophysiology and the treatment of psychosis in WD, and its association with neurological, liver and ophthalmic manifestations.

Immediate effects of cigar smoking on respiratory mechanics and exhaled biomarkers; differences between young smokers with mild asthma and otherwise healthy young smokers.

BACKGROUND: We aimed to investigate the immediate respiratory effects of cigar smoking(CS), among young smokers with and without mild asthma. MATERIALS AND METHODS: Forty-seven young smokers (18-31years old, 29 males, average pack-years = 3.6 ± 2.8) were enrolled. Twenty-two were mild asthmatics(MA-subgroup) and the remaining 25 were otherwise healthy smokers(HS-subgroup). Exhaled carbon monoxide(eCO), multi-frequency respiratory system impedance(Z), resistance(R), reactance(X), frequency-dependence of resistance(fdr = R5Hz - R20Hz), resonant frequency(fres), reactance area(AX) and exhaled nitric oxide(FENO) were measured at the aforementioned sequence, before and immediately after 30 min of CS, or equal session in the smoking area while using a sham cigar(control group). Chi-square, student's t-tests, mixed linear models and Pearson correlation tests were used for the statistical analysis; level of significance was defined as p < 0.05. RESULTS: Immediately after CS, Z5Hz, R5Hz, R10Hz, R20Hz and eCO increased significantly in both subgroups(MA and HS). A greater increase was found for R20 in HS-subgroup. Fdr, fres and AX increased in MA, while decreased in HS. On the contrary, X10 decreased in MA and increased in HS, while X20 showed a greater decrease in MA. Changes in fdr, fres and AX were significantly correlated in both subgroups. No significant FENO alterations were detected in both subgroups. CONCLUSION: CS has immediate effects on pulmonary function. Mild asthma predisposes to higher increase of peripheral resistance(increased fdr). In otherwise healthy smokers, central resistance(R20Hz) is more affected. FENO levels are not significantly affected by CS.

Exhaled Breath Condensate: Technical and Diagnostic Aspects.

PURPOSE: The aim of this study was to evaluate the 30-year progress of research on exhaled breath condensate in a disease-based approach. METHODS: We searched PubMed/Medline, ScienceDirect, and Google Scholar using the following keywords: exhaled breath condensate (EBC), biomarkers, pH, asthma, gastroesophageal reflux (GERD), smoking, COPD, lung cancer, NSCLC, mechanical ventilation, cystic fibrosis, pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis, interstitial lung diseases, obstructive sleep apnea (OSA), and drugs. RESULTS: We found 12600 related articles in total in Google Scholar, 1807 in ScienceDirect, and 1081 in PubMed/Medline, published from 1980 to October 2014. 228 original investigation and review articles were eligible. CONCLUSIONS: There is rapidly increasing number of innovative articles, covering all the areas of modern respiratory medicine and expanding EBC potential clinical applications to other fields of internal medicine. However, the majority of published papers represent the results of small-scale studies and thus current knowledge must be further evaluated in large cohorts. In regard to the potential clinical use of EBC-analysis, several limitations must be pointed out, including poor reproducibility of biomarkers and absence of large surveys towards determination of reference-normal values. In conclusion, contemporary EBC-analysis is an intriguing achievement, but still in early stage when it comes to its application in clinical practice.