Depression is among the most common psychiatric illnesses, which imposes a major socioeconomic burden on patients, caregivers, and the public health system. Treatment with classical antidepressants (e.g. tricyclic antidepressants and selective serotonine reuptake inhibitors), which primarily affect monoaminergic systems has several limitations, such as delayed onset of action and moderate efficacy in a relatively large proportion of depressed patients. Furthermore, depression is highly heterogeneus, and its different subtypes, including post-partum depression, involve distinct neurobiology, warranting a differential approach to pharmacotherapy. Given these shortcomings, the need for novel antidepressants that are superior in efficacy and faster in onset of action is fully justified. The development and market introduction of rapid-acting antidepressants has accelerated in recent years. Some of these new antidepressants act through the GABAergic system. In this review, we discuss the discovery, efficacy, and limitations of treatment with classic antidepressants. We provide a detailed discussion of GABAergic neurotransmission, with a special focus on GABAA receptors, and possible explanations for the mood-enhancing effects of GABAergic medications (in particular neurosteroids acting at GABAA receptors), and ultimately, we present the most promising molecules belonging to this family which are currently used in clinical practice or are in late phases of clinical development.

Hyponatremia is the most frequent electrolyte imbalance in geriatric medicine. Causes of hyponatremia were retrospectively analyzed in all in-patients treated in 2016 (N = 2267, 1564 women, 703 men, mean age ± standard deviation 81.9 ± 7.6 years). Any form of hyponatremia on admission, during the stay or on discharge was noted in 308 patients (13.6%, 231 women, 77 men; mean age ± standard deviation 83.1 ± 7.3 years, p = 0.009 vs. age of all patients). Women had a higher probability of developing hyponatremia compared to men (p = 0.019), 131 patients were hypovolemic, and dyspnea as an indicator of hypervolemia was noted in 71 patients.Only 12 patients suffering from hyponatremia (3.9%) did not receive any of the potentially sodium-lowering drugs assessed (diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, antidepressants, neuroleptics, nonsteroidal antirheumatics, carbamazepine, oxcarbazepine). The median number of drugs per patient potentially lowering the plasma sodium level was 3 and the maximum number was 7.Hypovolemic hyponatremia and the syndrome of inadequate antidiuretic hormone secretion were the most important causes of hyponatremia. Adverse drug effects were the main origins of both conditions. In patients with hyponatremia the drug load influencing plasma sodium level should be minimized, thiazide diuretics should be avoided and older individuals should receive a diet with sufficient salt content.
UNASSIGNED: Die Hyponatriämie ist die häufigste Elektrolytstörung in der geriatrischen Medizin. Mögliche Ursachen der Hyponatriämie wurden retrospektiv bei allen stationären Patienten im Jahr 2016 evaluiert (N = 2267 [1564 Frauen, 703 Männer], Alter 81,9 ± 7,6 Jahre [Mittelwert ± Standardabweichung]). Irgendeine Form der Hyponatriämie bei Krankenhausaufnahme, während des Aufenthalts oder bei Entlassung wurde bei 308 Patienten (13,6 % [231 Frauen, 77 Männer; Durchschnittsalter ± Standardabweichung 83,1 ± 7,3; p = 0,009 im Vergleich zum Alter aller Patienten]) festgestellt. Die Wahrscheinlichkeit, eine Hyponatriämie zu entwickeln, lag bei Frauen höher als bei Männern (p = 0,019). 131 Patienten waren hypovolämisch, und bei 71 Patienten war eine Dyspnoe als Hinweis für eine Hypervolämie dokumentiert. Nur 12 Patienten mit einer Hyponatriämie (3,9 %) erhielten keines der ausgewerteten, potenziell die Plasma-Natrium-Konzentration senkenden Medikamente (Diuretika, Angiotensin-Converting-Enzyme-Inhibitoren, Angiotensin-II-Rezeptor-Antagonisten, Antidepressiva, Neuroleptika, nichtsteroidale Antirheumatika, Carbamazepin, Oxcarbazepin). Im Median lag die Zahl der potenziell den Plasma-Natrium-Spiegel senkenden Medikamente pro Patient bei 3, die höchste Zahl war 7. Hypovolämische Hyponatriämie und das Syndrom der inadäquaten ADH-Sekretion waren die wichtigsten Ursachen einer Hyponatriämie. Beide Zustände wurden am häufigsten durch unerwünschte Medikamentenwirkungen ausgelöst. Patienten mit Hyponatriämie sollten möglichst wenige Medikamente erhalten, die den Plasma-Natrium-Spiegel senken können. Thiaziddiuretika sollten vollständig vermieden werden, und ältere Personen sollten mit der Nahrung ausreichend Salz zu sich nehmen.

BACKGROUND: The World Health Organization reports that depression affects more than 280 million people globally. Women are approximately 50% more likely to experience depression compared to men. Depression during pregnancy leads to deterioration of the mother\'s and the fetus\'s health. We aim to explore women\'s perceptions and attitudes toward using antidepressants and to identify the factors that influence decision-making regarding antidepressant use.
METHODS: A cross-sectional survey, employing a convenience sampling method, was conducted on a university campus in Riyadh, Saudi Arabia. The survey was developed by the investigators and validated by health practitioners. Answers were reported using a 5-point Likert scale. The responses were summed up to give a total score for each respondent. Respondents who scored above or equal 75% of the total score was considered positive perception or favorable attitude. Binary logistic regression analysis was used to identify factors influencing participants\' perception and attitude toward taking antidepressants.
RESULTS: A total of 991 subjects were surveyed. The majority of women had negative perceptions and favorable attitudes towards using antidepressants during pregnancy reaching 64%. While women with positive perceptions and favorable attitudes represented about 20% of the study subjects. Participants reported that social stigma, religious beliefs, and fear of addiction significantly influenced their attitudes toward antidepressant use.
CONCLUSIONS: This study explores women\'s perceptions of depression and antidepressant use, revealing that a significant proportion of Saudi women have a negative perception. The research emphasizes the need for tailored awareness programs to promote informed decision-making regarding antidepressant usage among Saudi women.

Major depressive disorder (MDD) is associated with disruptions in glutamatergic and GABAergic activity in the medial prefrontal cortex (mPFC), leading to altered synaptic formation and function. Low doses of ketamine rapidly rescue these deficits, inducing fast and sustained antidepressant effects. While it is suggested that ketamine produces a rapid glutamatergic enhancement in the mPFC, the temporal dynamics and the involvement of GABA interneurons in its sustained effects remain unclear. Using simultaneous photometry recordings of calcium activity in mPFC pyramidal and GABA neurons, as well as chemogenetic approaches in Gad1-Cre mice, we explored the hypothesis that initial effects of ketamine on glutamate signaling trigger subsequent enhancement of GABAergic responses, contributing to its sustained antidepressant responses. Calcium recordings revealed a biphasic effect of ketamine on activity of mPFC GABA neurons, characterized by an initial transient decrease (phase 1, <30 min) followed by an increase (phase 2, >60 min), in parallel with a transient increase in excitation/inhibition levels (10 min) and lasting enhancement of glutamatergic activity (30-120 min). Previous administration of ketamine enhanced GABA neuron activity during the sucrose splash test (SUST) and novelty suppressed feeding test (NSFT), 24 h and 72 h post-treatment, respectively. Chemogenetic inhibition of GABA interneurons during the surge of GABAergic activity (phase 2), or immediately before the SUST or NSFT, occluded ketamine\'s behavioral actions. These results indicate that time-dependent modulation of GABAergic activity is required for the sustained antidepressant-like responses induced by ketamine, suggesting that approaches to enhance GABAergic plasticity and function are promising therapeutic targets for antidepressant development.

UNASSIGNED: Late adolescents and young adults (AYA) with inflammatory bowel disease (IBD) are a vulnerable population as they transition to adult healthcare. We aim to provide a real-world data on their healthcare utilization patterns and medication use through a large database.
UNASSIGNED: We performed a retrospective cohort study from January 1, 2012, to June 30, 2020, using OneFlorida Data-Trust, an electronic health record-based data repository representing over half of the Florida population. Outcomes of interest included demographics, healthcare utilization, medications, and disease severity. Chi-square tests and logistic regression were used to compare the rates of medication use, healthcare utilization, and disease severity by age groups.
UNASSIGNED: The number of patients who met our inclusion criteria was 10,578 with 2731 (25.8%) in the 17-25-year-old group. AYA patients had fewer ambulatory visits vs children (90% vs 95%; P value <.05). AYA patients were admitted more frequently from emergency facilities vs children (22.3% vs 10.9%; P value <.05). AYA patients received steroids more often than adults and younger patients (48.9% vs 45.3 vs 44.3% P value <.05, respectively). AYA patients received more narcotic (41.1% vs 22.3 % P value <.05) and antidepressant prescriptions (15.9% vs 9.5%; P value <.05) compared with children. With advancing age, a decrease in biologic use was noted (51% vs 40% vs 25.4% P value <.05, respectively).
UNASSIGNED: AYA patients with IBD have higher rates of hospital admissions from emergency department, fewer ambulatory health visits and they receive more steroids compared to children. Our study demonstrates the need for age-specific IBD programs for AYA patients.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are medications used in child and adolescent psychiatry mainly for the treatment of depression, anxiety and obsessive compulsive disorder. In general, these medications are safe and well tolerated. However, they can cause adverse effects such as activation syndrome, which if not identified can negatively affect adherence and response to treatment. Activation syndrome has received little attention and can be difficult to recognise due to the lack of a clear definition and objective diagnostic measures, and also because it can be confused with a worsening of the psychiatric disorder or mania triggered by the antidepressants. For all the above, it is important that professionals who prescribe antidepressants in the paediatric population are able to identify and manage activation syndrome when it occurs. Our aim was to carry out a narrative review of activation syndrome in children and adolescents treated with SSRIs in terms of definition, prevalence, pathophysiology, associated factors, relationship with suicide risk, management strategies and recommendations for reducing the risk of suicidal behaviours when using antidepressants in this population.
METHODS: We performed a non-systematic narrative review of activation syndrome in children and adolescents which involved finding information in PubMed, Ovid, EBSCO, ProQuest and Embase. Review articles, prospective and retrospective investigations, systematic reviews, meta-analyses and other articles related to activation syndrome in children and adolescents were selected. The search was limited to studies published in English and Spanish that involved children and adolescents and no limits were applied to the publication date or study design.
RESULTS: A total of 62 articles were included, 61 of them in English. The results were grouped into the following topics: definition; prevalence; pathophysiology; associated factors; relationship with suicide risk; management strategies; and recommendations for reducing the risk of suicidal behaviours when using antidepressants in this population. Activation syndrome refers to a set of symptoms consisting of impulsiveness, restlessness, increased activity, insomnia, irritability, disinhibition and agitation. This syndrome is poorly characterised in terms of its definition, prevalence, risk factors and pathophysiology, a situation that limits its recognition and evaluation. There are many factors that predispose the development of the syndrome such as age, differences in brain development in the paediatric population, the characteristics of the patient or the antidepressant, disorders of neurological development, and the doses and plasma levels of the medications. It has been thought that activation syndrome may be related to suicidal tendencies. However, the evidence in support of this link is inconsistent and further studies are therefore necessary.
CONCLUSIONS: Activation syndrome with SSRI is a particularly important adverse effect in children and adolescents and, when it occurs, can cause lack of adherence to or discontinuation of treatment. Strict vigilance is therefore recommended during the use of these medications.

UNASSIGNED: Chronic pain presents a multifaceted challenge in clinical practice, necessitating a nuanced understanding of pharmacological interventions to optimize treatment outcomes. This review provides an outline of various pharmacological agents commonly used in chronic pain management and highlights their safety considerations, particularly regarding suicide risk.
UNASSIGNED: This review discusses the role of antidepressants, anticonvulsants, GABA receptor agonists, NMDA receptor antagonists, corticosteroids, cannabis and cannabinoids, bisphosphonates, calcitonin, and alpha-2 adrenergic receptor agonists in chronic pain management. It assesses their therapeutic benefits, potential for misuse, and psychiatric adverse effects, including the risk of suicide. Each pharmacological class is evaluated in terms of its efficacy, safety profile, and considerations for clinical practice. We searched peer-reviewed English literature on the topic using the MEDLINE database without time restrictions.
UNASSIGNED: While pharmacological interventions offer promise in alleviating chronic pain, healthcare providers must carefully weigh their benefits against potential risks, including the risk of exacerbating psychiatric symptoms and increasing suicide risk. Individualized treatment approaches, close monitoring, and multidisciplinary collaboration are essential for optimizing pain management strategies while mitigating adverse effects. Ongoing research efforts are crucial for advancing our understanding of these pharmacological interventions and refining pain management practices.

Depression is a chronic mental disorder characterized by persistent low mood and loss of interest. Treatments for depression are varied but may not be sufficient cure. Drug-based treatment regimens have drawbacks such as slow onset of action, low bioavailability, and drug side effects. Nanocarrier Drug Delivery Systems (NDDS) has received increasing attention for brain drug delivery since it assists the drug through the blood-brain barrier and improves bioavailability, which may be beneficial for treating depression. Due to the particle size and physicochemical properties of nanocarriers, it presents a promise to improve the stability and solubility of antidepressants, thereby enhancing the drug concentration. Moreover, ligand-modified nanocarriers can be taken as a target direct medicines release system and reduce drug side effects. The purpose of the present review is to provide an up-to-date understanding of the Nanocarrier drug delivery system and relevant antidepressants in different routes of ingestion, to lay a foundation for the treatment of patients with depression.

UNASSIGNED: This study identifies patterns of antidepressant prescribing and subsequent hospital admissions from 2010 to 2018 amongst older adults in Northern Ireland (NI).
UNASSIGNED: Participants comprised all General Practitioner (GP)-registered adults aged fifty-five years and above on 01/01/2010 (n = 386,119). Administrative data linkage included demographic information; antidepressant prescribing data from the NI Enhanced Prescribing Database (EPD); and hospital patient admissions. Repeated measures latent class analysis (RMLCA) identified patterns of antidepressant prescribing (from 2010 to 2018).
UNASSIGNED: RMLCA identified four latent classes: decreasing antidepressant prescribing (5.9%); increasing antidepressant prescribing (8.0%); no-antidepressant prescribing (68.7%); and long-term antidepressant prescribing (17.5%). Compared with those in no-antidepressant prescribing class, persons in the remaining classes were more likely to be female and younger, and less likely to live in either rural areas or less-deprived areas. Compared with no-antidepressant prescribing, those with increasing antidepressant prescribing were 60% and 52% more likely to be admitted to hospital in 2019 and 2020, respectively, and their admission rate per year was 11% and 8% higher in 2019 and 2020, respectively. Similarly, those with long-term prescriptions were 70% and 67% more likely to be admitted to hospital in 2019 and 2020, respectively, and their admission rate per year was 14% and 9% higher in 2019 and 2020, respectively.
UNASSIGNED: Findings show that approximately 26% of the NI hospital admissions population were impacted by sustained or increasing antidepressant prescribing. Because of their increased likelihood of hospitalization, these individuals may benefit from psychosocial support and social prescribing alternatives to psychopharmacological treatment.

BACKGROUND: The serotonin 4 receptor (5-HT4R) is a promising target for the treatment of depression. Highly selective 5-HT4R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established.
OBJECTIVE: To determine whether prucalopride (a 5-HT4R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system.
METHODS: Using anonymised routinely collected data from a large-scale USA electronic health records network, we conducted an emulated target trial comparing depression incidence over 1 year in individuals without prior diagnoses of major mental illness, who initiated treatment with prucalopride versus two alternative anti-constipation agents that act by different mechanisms (linaclotide and lubiprostone). Cohorts were matched for 121 covariates capturing sociodemographic factors, and historical and/or concurrent comorbidities and medications. The primary outcome was a first diagnosis of major depressive disorder (ICD-10 code F32) within 1 year of the index date. Robustness of the results to changes in model and population specification was tested. Secondary outcomes included a first diagnosis of six other neuropsychiatric disorders.
RESULTS: Treatment with prucalopride was associated with significantly lower incidence of depression in the following year compared with linaclotide (hazard ratio 0.87, 95% CI 0.76-0.99; P = 0.038; n = 8572 in each matched cohort) and lubiprostone (hazard ratio 0.79, 95% CI 0.69-0.91; P < 0.001; n = 8281). Significantly lower risks of all mood disorders and psychosis were also observed. Results were similar across robustness analyses.
CONCLUSIONS: These findings support preclinical data and suggest a role for 5-HT4R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting.