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Purpose: Educational attainment has been shown to be positively associated with mental health and a potential buffer to stressful events. One stressful life event likely to affect everyone in their lifetime is bereavement. This paper assesses the effect of educational attainment on mental health post-bereavement.Methods: By utilising large administrative datasets, linking Census returns to death records and prescribed medication data, we analysed the bereavement exposure of 208,332 individuals aged 25-74 years. Two-level multi-level logistic regression models were constructed to determine the likelihood of antidepressant medication use (a proxy of mental ill health) post-bereavement given level of educational attainment.Results: Individuals who are bereaved have greater antidepressant use than those who are not bereaved, with over a quarter (26.5 %) of those bereaved by suicide in receipt of antidepressant medication compared to just 12.4 % of those not bereaved. Within individuals bereaved by a sudden death, those with a university degree or higher qualifications are 73 % less likely to be in receipt of antidepressant medication compared to those with no qualifications, after full adjustment for demographic, socio-economic and area factors (OR 0.27, 95 % CI 0.09,0.75). Higher educational attainment and no qualifications have an equivalent effect for those bereaved by suicide.Conclusions: Education may protect against poor mental health, as measured by the use of antidepressant medication, post-bereavement, except in those bereaved by suicide. This is likely due to the improved cognitive, personal and psychological skills gained from time spent in education. [ABSTRACT FROM AUTHOR]

Bupleurum scorzonerifolium (BS) is one of the sources of Bupleuri Radix, which was first recorded in Shennong's classic of materia medica. It has a medicinal history of 2000 years and is now widely used for the treatment of depression clinically. However, the material basis of antidepressant effects is unclear, and the quality evaluation method is lacking. The paper aims to investigate the antidepressant quality markers (Q-markers) of BS by electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS). Firstly, the rat depression model was established by using chronic unpredictable mild stress (CUMS) combined with the solitary confinement method to evaluate the pharmacodynamics of BS. After verification of the antidepressant effect of BS, UPLC-ESI-Q-TOF-MS was used to analyze BS and the blood components of BS. A total of 34 components were identified in BS, in which 8 components, including saikosaponin a (SSa), saikosaponin c (SSc), saikosaponin d (SSd), saikosaponin b 1 (SSb 1), saikosaponin b 2 (SSb 2), glycyrrhetinic acid, nootkatone and valerenic acid, were detected in serum. SSa, SSc, SSd, SSb 1 and SSb 2 were found as metabolites, and glycyrrhetinic acid, nootkatone and valerenic Acid were identified as the prototypes in the blood. The depression model of zebrafish was established with reserpine to verify the antidepressant effect of the potential eight active components. The results showed that all these components could markedly improve the depressive behavior of zebrafish, increase the content of 5-HT and reduce the cortisol content. Finally, according to the principles of effectiveness, accessibility and measurability for Q-markers, SSa, SSc, and SSd were confirmed as Q-markers of BS, and the contents of 3 Q-markers in 10 batches of BS from different origins were determined to be 0.0728–1.465%. In addition, the total contents of 3 Q-markers in BS produced in Lindian, Heilongjiang Province, were higher than those in other origins. This paper provided a reliable method for the quality evaluation of BS for depression treatment. [Display omitted] • Eight antidepressant components of BS have been discovered. • 34 components of BS have been analyzed and identified. • SSa, SSc and SSd have been identified as anti-depression Q-markers of BS. • HPLC-ELSD detection method for anti-depression Q-markers have been established. [ABSTRACT FROM AUTHOR]

Rationale: In recent decades, the use of ayahuasca (AYA) - a β-carboline- and dimethyltryptamine-rich hallucinogenic botanical preparation traditionally used by Northwestern Amazonian tribes for ritual and therapeutic purposes - has spread from South America to Europe and the USA, raising concerns about its possible toxicity and hopes of its therapeutic potential. Thus, it is important to analyze the acute, subacute, and long-term effects of AYA to assess its safety and toxicity.Objectives: The purpose of this study was to conduct a systematic review of human studies assessing AYA effects on psychiatric symptoms, neuropsychological functioning, and neuroimaging.Methods: Papers published until 16 December 2015 were included from PubMed, LILACS and SciELO databases following a comprehensive search strategy and pre-determined set of criteria for article selection.Results: The review included 28 full-text articles. Acute AYA administration was well tolerated, increased introspection and positive mood, altered visual perceptions, activated frontal and paralimbic regions and decreased default mode network activity. It also improved planning and inhibitory control and impaired working memory, and showed antidepressive and antiaddictive potentials. Long-term AYA use was associated with increased cortical thickness of the anterior cingulate cortex and cortical thinning of the posterior cingulate cortex, which was inversely correlated to age of onset, intensity of prior AYA use, and spirituality. Subacute and long-term AYA use was not associated with increased psychopathology or cognitive deficits, being associated with enhanced mood and cognition, increased spirituality, and reduced impulsivity.Conclusions: Acute, subacute, and long-term AYA use seems to have low toxicity. Preliminary studies about potential therapeutic effects of AYA need replication due to their methodological limitations. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for patients with depression who have not achieved optimal outcomes with one or more trials of antidepressant medication. It is an effective antidepressant treatment but there remains considerable scope for improving clinical outcomes. One method to potentially enhance the efficacy of rTMS is through the improvement of methods of stimulation localization. The purpose of this paper is to review the literature pertaining to rTMS localization methods and approaches relevant to the treatment of major depressive disorder (MDD) and provide specific opinions on the state of the art in regards to targeting of rTMS treatment in depression. A targeted review of the literature on rTMS targeting in depression. There is emerging evidence that optimal rTMS treatment outcomes are likely to be achieved with stimulation at a relatively anterior stimulation site in the left dorsolateral prefrontal cortex (DLPFC). However, some lines of research suggest that there may be two effective stimulation sites: one quite posterior, and one more anterior, in the DLPFC. The 'Beam F3' method provides reasonable localization to the anterior stimulation site and the posterior stimulation site corresponds to that typically used in studies using the '5 cm method'. Neuro-navigational methods are generally most likely to consistently ensure placement of the TMS coil such that it results in stimulation of a selected cortical site. fMRI – connectivity based approaches to targeting specific circuits in the DLPFC are intellectually attractive but it may not be possible to demonstrate differential effectiveness of these over the methods most commonly been used in clinical practice. There is an emerging literature helping to improve our understanding of the optimal methods for targeting rTMS treatment for depression. However, we lack substantive prospective clinical trials demonstrating improved clinical outcomes with these techniques. • rTMS is an effective treatment for MDD and response rates should be able to be improved by enhanced methods for targeting. • Clinical responses seem to be better when treatment is provided at sites more anterior and lateral in the DLPFC. • There is emerging evidence that antidepressant responses may be achieved by stimulation of two separate sites. • The Beam F3 approach is a good method for targeting of stimulation at the more anterior stimulation site within the DLPFC. • Connectivity analysis of resting state fMRI data has potential to be used in the personalisation of stimulation targeting. [ABSTRACT FROM AUTHOR]

Background: Depression is a severe mental disorder that poses a significant threat to both the physical and mental wellbeing of individuals. Currently, there are various methods for treating depression, including traditional Chinese herbal formulations like Chaihu-Shugan-San (CSS), which have shown effective antidepressant effects in both clinical and animal research. Objective: This review aims to provide a comprehensive synthesis of evidence related to CSS, considering both preclinical and clinical studies, to uncover its potential multi-level, multi-pathway, and multi-target mechanisms for treating depression and identify its active ingredients. Methods: A thorough search was conducted in electronic databases, including PubMed, MEDLINE, Web of Science, Google Scholar, CNKI, and Wanfang, using keywords such as "Chaihu Shugan" and "depression" to retrieve relevant literature on CSS and its active ingredients. The review process adhered to the PRISMA guidelines. Results: This review consolidates the mechanisms underlying antidepressant effects of CSS and its active ingredients. It emphasizes its involvement in the regulation of monoaminergic neurotransmitter systems, synaptic plasticity, and the hypothalamic-pituitary-adrenal axis, among other aspects. Conclusion: CSS exerts a pivotal role in treating depression through various pathways, including the monoaminergic neurotransmitter system, the hypothalamic-pituitary-adrenal axis, synaptic plasticity, inflammation, brainderived neurotrophic factor levels, and the brain-gut axis. This review facilitates a comprehensive understanding of the current state of CSS research, fostering an in-depth exploration of the etiological mechanisms of depression and the potential discovery of novel antidepressant drugs. [ABSTRACT FROM AUTHOR]

Prenatal depression affects approximately 10% to 15% of women. Guidelines recommend supporting women to make informed treatment decisions; however, minimal evidence exists regarding this decision-making process. This study aimed to develop a constructivist grounded theory of prenatal antidepressant treatment decision-making. Semi-structured interviews were conducted with purposively sampled women from the community or specialty clinics (N = 31). Iterative data collection and analysis, theoretical sampling, and member checking supported model sufficiency. In the Creating Comfort in Choice theory that we developed, participants were highly conscious of societal stigma toward mental illness and prenatal medication use, so fear, anxiety, and guilt dominated decision-making. Participants navigated dynamically among three clusters of decision-making activities: seeking information, making sense of information, and self-soothing. "Seeking information" included internal and external processes. In "making sense of information," participants appraised available evidence. In "self-soothing," participants engaged in coping strategies to try to alleviate painful emotions. The Creating Comfort in Choice theory can support patient-oriented decision-making regarding prenatal mental healthcare. [ABSTRACT FROM AUTHOR]

Background Depression is one of the most common psychological disorders that can affect a person’s mood and change his/her perception of the self and environment. Melilotus officinalis L. plant contains effective substances and antioxidant compounds. Objective The present study aims to investigate the antidepressant effects of alcoholic extract of Melilotus officinalis L. in male rats. Methods In this experimental research, 42 male rats were divided into six groups of 7 including control (normal saline), negative control (reserpine), positive control (reserpine+fluoxetine) and three reserpine groups treated by intraperitoneal injection of 100, 200, 400 mg/kg doses of alcoholic extract of Melilotus officinalis L. Behavioral tests including forced swim test (FST) and tail suspension test (TST) were used to evaluate depression, and the antioxidant capacity and malondialdehyde level were also measured. The data were analyzed in SPSS software, version 20 using one-way analysis of variance. The significance level was set at P<0.05. Results The 200 mg/kg and 400 mg/kg doses of alcoholic extract significantly reduced the duration of immobility in the FST compared to the negative control. In the TST, the doses of 200 and 400 mg/kg showed a significant increase compared to the negative control. The doses of 200 and 400 mg/kg significantly increased the antioxidant capacity of the brain compared to the negative control. The doses of 200 and 400 mg/kg significantly reduced the antioxidant capacity of the brain compared to the negative control. Conclusion The alcoholic extract of Melilotus officinalis L has antidepressant effects similar to fluoxetine probably due to its antioxidant compounds. [ABSTRACT FROM AUTHOR]

The incidence of depression has been steadily rising in recent years, making it one of the most prevalent mental illnesses. As the pursuit of novel antidepressant drugs captivates the pharmaceutical field, the therapeutic efficacy of Traditional Chinese Medicine (TCM) has been widely explored. Chaihu (Bupleurum) has been traditionally used for liver conditions such as hepatitis, liver inflammation, liver fibrosis, and liver cancer. It is believed to have hepatoprotective effects, promoting liver cell regeneration and protecting against liver damage. In addition, Bupleurum has also been used as a Jie Yu (depression-relieving) medicine in China, Japan, Republic of Korea, and other Asian countries for centuries. This review article aims to summarize the research conducted on the antidepressant properties and mechanisms of Bupleurum, as well as discuss the potential of TCM formulas containing Bupleurum. This review highlights various antidepressant ingredients isolated from Bupleurum, including saikosaponin A, saikosaponin D, rutin, puerarin, and quercetin, each with distinct mechanisms of action. Additionally, Chinese herb prescriptions and extracts containing Bupleurum, such as Chaihu Shugansan, Xiaoyaosan, and Sinisan, are also included due to their demonstrated antidepressant effects. This review reveals that these Bupleurum compounds exhibit antidepressant effects through the regulation of neurotransmitter mechanisms (such as 5-HT and DA), the NMDA (N-methyl-D-aspartate) system, brain-derived neurotrophic factor (BDNF), and other intracellular signaling pathways. Collectively, this comprehensive review provides insights into the multiple applications of Bupleurum in the treatment of depression and highlights its potential as an alternative or complementary approach to traditional therapies. However, it is essential to consider the potential adverse effects and clinical restrictions of Bupleurum despite its promising potential. Further research is needed to elucidate its specific mechanisms of action and evaluate its effectiveness in human subjects. [ABSTRACT FROM AUTHOR]

Introduction: Plants and their extracts have been integral to the development of medicinal treatments throughout history, offering a vast array of compounds for innovative therapies. Baccaurea motleyana Müll. Arg., commonly known as Rambai, is an evergreen tree with economic importance in the Old- World Tropics. Method: The study investigates its phytochemical composition through Gas Chromatography-Mass Spectrometry (GC-MS) and evaluates its pharmacological properties, including antidiabetic, antidiarrheal, antimicrobial, and antidepressant effects. Result and Discussion: The GC-MS analysis revealed 15 bioactive compounds in the methanol extract, with Phenol, 3,5-bis(1,1-dimethylethyl)-, Methyl stearate, and Hexadecanoic acid, methyl ester being the predominant ones. The cytotoxicity assay demonstrated significant activity in the ethyl acetate fraction. Antimicrobial assays indicated mild to moderate antibacterial activity. In vivo studies on mice revealed significant hypoglycemic, antidiarrheal, and antidepressant properties. Molecular docking studies against EGFR, DHFR, GLUT- 3, KOR, and MOA identified promising compounds with potential therapeutic effects. The identified compounds exhibited favorable ADME/T properties, emphasizing their potential for drug development. The study underscores the promising therapeutic potential of Baccaurea motleyana, showcasing its diverse bioactive compounds with significant medicinal properties. Conclusion: These findings lay the groundwork for future research, emphasizing the exploration of B. motleyana as a source of natural remedies for addressing prevalent health conditions. [ABSTRACT FROM AUTHOR]

Bupropion (Bup) belongs to the norepinephrine–dopamine reuptake inhibitor (NDRI) class and it is the only FDA-approved drug of its class for the treatment of major depressive disorder (MDD), sold under the name of Wellbutrin. Although bupropion is effective in suppressing the symptoms, its regular use and overdose might lead to seizures and liver failure. Thus, we aimed to nanoformulate bupropion onto a niosomal vesicle to improve its efficacy and achieve the same therapeutic effect at lower scheduled doses. A thin film hydration method was adopted to synthesize and optimize Bup entrapped niosomes using three different surfactants of the sorbitan ester series (Span 20, 40, and 60) in combination with cholesterol. The optimization data determined that the niosome formulated with a cholesterol-to-surfactant ratio of 1:1.5 is the most stable system, with the Bup entrapped niosomes containing Span 20 (Bup@N20C) exhibiting minimal in vitro and in vivo toxicity, and demonstrating the sustained release of Bup in artificial cerebrospinal fluid (ACSF). The Bup@N20C formulation showed increased exploration activity and reduced irregular movements in reserpine-induced depression in the adult zebrafish model, suggesting the potential for mood improvement through the suppression of depression-like behavior which was established by statistical analysis and trajectory data. The Bup@N20C-treated group even surpasses the treatment effect of the positive control group and is comparable to the control group. Hence, it can be inferred that niosomal formulations of Bup represent a promising delivery system capable of achieving the brain delivery of the cargo by bypassing the blood–brain barrier facilitated by their small architectural structure. [ABSTRACT FROM AUTHOR]

Fluoxetine (FLX) is one of the most persistent pharmaceuticals found in wastewater due to increased use of antidepressant drugs in recent decades. In this study, a nanocomposite of ternary ZnCoAl layered double hydroxide supported on activated carbon (LAC) was used as an adsorbent for FLX in wastewater effluents. The nanocomposite was characterized using Fourier Transform Infrared Spectroscopy (FTIR), scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), and surface area analysis (BET). The adsorption investigations showed that the maximum removal capacity was achieved at pH 10, with a 0.1 g/L adsorbent dose, 50 mL volume of solution, and at a temperature of 25 °C. The FLX adsorption process followed the Langmuir–Freundlich model with a maximum adsorption capacity of 450.92 mg/g at FLX concentration of 50 µg/mL. Density functional theory (DFT) computations were used to study the adsorption mechanism of FLX and its protonated species. The safety and toxicity of the nanocomposite formed from the adsorption of FLX onto LAC (FLX-LAC) was investigated in male albino rats. Acute toxicity was evaluated using probit analysis after 2, 6, and 24 h to determine LD50 and LD100 values in a rat model. The FLX-LAC (20 mg/kg) significantly increased and lengthened the sleep time of the rats, which is important, especially with commonly used antidepressants, compared to the pure standard FLX (7 mg/kg), regular thiopental sodium medicine (30 mg/kg), and LAC alone (9 mg/kg). This study demonstrated the safety and longer sleeping duration in insomniac patients after single-dose therapy with FLX-LAC. Selective serotonin reuptake inhibitors (SSRIs) like FLX were found to have decreased side effects and were considered the first-line mood disorder therapies. [ABSTRACT FROM AUTHOR]

Background: Our knowledge of the broader impacts of antidepressant withdrawal, beyond physical side effects, is limited. Further research is needed to investigate the lived experiences of withdrawal, to aid clinicians on how to guide patients through the process. Aim: To explore antidepressant users' experiences and views on the withdrawal process and how it affected their quality of life across multiple life domains. Design and Setting: We conducted in‐depth qualitative interviews with 20 individuals from the community who had attempted to withdraw from Serotonin Reuptake Inhibitor antidepressants in the past year. Method: Semi‐structured interviews were conducted online. A topic guide was used to ensure consistency across interviews. The interviews were audio‐recorded and transcribed verbatim and analysed using inductive reflexive thematic analysis. Results: Five themes were generated. The first highlighted the challenges of managing the release from emotional blunting and cognitive suppression following antidepressant discontinuation. The second related to the negative impact of withdrawal on close relationships and social interactions. The third showed that concurrent with negative physical symptoms, there was a positive impact on health (exercise was reported by some as a coping mechanism). The fourth theme focused on support from GPs and families, emphasising the importance of mental health literacy in others. The final theme underscored the importance of gradual and flexible tapering in enabling a manageable withdrawal experience, and the consideration of timing. Conclusion: The lived experience of withdrawal significantly impacts individuals' well‐being. Participants emphasised that withdrawal is not just about physical side effects but also affects their emotional, cognitive, and social functioning. Patient and Public Involvement (PPI): Eight people attended individual online meetings to share their experiences of antidepressant withdrawal to help inform the study design and recruitment strategy. Insights from these meetings informed the development of the topic guide. Questions about GP involvement, family relationships, and mood and thinking changes were included based on this PPI work. This ensured the inclusion of topics important to antidepressant users and facilitated the researcher's questioning during the interviews. [ABSTRACT FROM AUTHOR]

Depression remains the major cause of global disease burden and affects individuals in all communities around the world. More than 300 million individuals worldwide suffer from depression. The objective of the present study was to evaluate the antidepressant activity of ethanol leaf extract of Entada africana (ELEEA) in mice. Preliminary phytochemical screening and acute toxicity studies of the extract were carried out using standard methods. Antidepressant activity screening of the extract was conducted using Tail Suspension Test (TST), Forced Swim Test (FST), and Open Field Test (OFT) in mice. Phytochemical screening shows the presence of terpenoids, steroids, cardiac glycosides, tannins, saponins, flavonoids and carbohydrates in the extract. The result of the acute toxicity studies revealed an LD50 value of 28.3 mg/kg body weight in mice. ELEEA at all the tested doses significantly (p < 0.05) reduced the duration of immobility of mice in TST compared to the normal saline (control) group. In the FST, the extract at doses of 2, 4 and 8 mg/kg body weight exhibited significant (p < 0.01) reduction in the immobility time when compared to the control group. However, in the OFT, ELEEA at doses of 2, 4 and 8 mg/kg body weight and diazepam (0.5 mg/kg) had no significant effect (p > 0.05) on the number of lines crossed by the mice compared to the control group. The results of our study suggest that the ethanol leaf extract of Entada africana has potential for use as an antidepressant agent. [ABSTRACT FROM AUTHOR]

Rationale: Current psychotropic medications have been shown to modulate immune activation. However, the effects of individual psychotropic agents on the immune system and how these might contribute to their efficacy remain largely unclear. Objective: This paper aims to review previous literature on the effects of antidepressants and antipsychotics on the immune system, with a systematic review of in vitro findings, and discuss the relevance of these effects for the response to treatment and future drug development. Results: Inflammatory markers have been associated with fluctuations in clinical status and with treatment response both in depression and psychosis. The in vitro literature on antidepressants shows that some antidepressants, such as clomipramine and fluoxetine, more consistently decrease pro-inflammatory cytokines (interleukin (IL)-6, interferon (IFN)-γ, tumour necrosis factor (TNF)-α), whilst others (mirtazapine and venlafaxine) tend to increase their levels. However, any overall conclusion is challenged by several inconsistent findings, which appear partly dependent on different methodological approaches used. The in vitro studies on antipsychotics are even less clear-cut showing pro- and anti-inflammatory activity for the same antipsychotic agent (haloperidol, clozapine, risperidone) across different studies. We also noted inconsistencies between in vivo and in vitro literature, which could partly be attributed to the interaction in vivo with various biological systems or lifestyle factors that can modulate the immune system. Conclusions: Inflammatory markers seem to hold potential for developing more individualised treatment strategies in the future. In this context, further research disentangling the differential immunomodulatory effects of different drugs could be used for tailoring treatment to specific individuals, according to their immune endophenotypes. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) remains a huge personal and societal encumbrance. Particularly burdensome is a virulent subtype of MDD, treatment resistant major depression (TMRD), which afflicts 15–30% of MDD patients. There has been recent interest in N-methyl-d-aspartate receptors (NMDARs) as targets for treatment of MDD and perhaps TMRD. To date, most pre-clinical and clinical studies have focused on ketamine, although psychotomimetic and other side effects may limit ketamine's utility. These considerations prompted a recent promising pilot clinical trial of nitrous oxide, an NMDAR antagonist that acts through a mechanism distinct from that of ketamine, in patients with severe TRMD. In this paper, we review the clinical picture of TRMD as a subtype of MDD, the evolution of ketamine as a fast-acting antidepressant, and clinical and basic science studies supporting the possible use of nitrous oxide as a rapid antidepressant. [ABSTRACT FROM AUTHOR]

Abstract Background Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects. Methods STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1–2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. Discussion Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. Trial registration ISRCTN, ISRCTN15984604 . Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an increasingly used treatment for patients with depression. The use of rTMS in depression is supported by over 20 years of clinical trials. There has been a significant increase in knowledge around the use of rTMS in recent years.Objective: The aim of this paper was to review the use of rTMS in depression to provide an update for rTMS practitioners and clinicians interested in the clinical use of this treatment.Methods: A targeted review of the literature around the use of rTMS treatment of depression with a specific focus on studies published in the last 3 years.Results: High-frequency rTMS applied to the left dorsolateral prefrontal cortex is an effective treatment for acute episodes of major depressive disorder. There are several additional methods of rTMS delivery that are supported by clinical trials and meta-analyses but no substantive evidence that any one approach is any more effective than any other. rTMS is effective in unipolar depression and most likely bipolar depression. rTMS courses may be repeated in the management of depressive relapse but there is less evidence for the use of rTMS in the maintenance phase.Conclusions: The science around the use of rTMS is rapidly evolving and there is a considerable need for practitioners to remain abreast of the current state of this literature and its implications for clinical practice. rTMS is an effective antidepressant treatment but its optimal use should be continually informed by knowledge of the state of the art. [ABSTRACT FROM AUTHOR]

Copyright of Dusunen Adam: Journal of Psychiatry & Neurological Sciences is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Antidepressants often disrupt sleep. Vortioxetine, a multimodal antidepressant acting through serotonin (5-HT) transporter (SERT) inhibition, 5-HT3, 5-HT7 and 5-HT1D receptor antagonism, 5-HT1B receptor partial agonism, and 5-HT1A receptor agonism, had fewer incidences of sleep-related adverse events reported in depressed patients. In the accompanying paper a polysomnographic electroencephalography (sleep-EEG) study of vortioxetine and paroxetine in healthy subjects indicated that at low/intermediate levels of SERT occupancy, vortioxetine affected rapid eye movement (REM) sleep differently than paroxetine. Here we investigated clinically meaningful doses (80-90% SERT occupancy) of vortioxetine and paroxetine on sleep-EEG in rats to further elucidate the serotoninergic receptor mechanisms mediating this difference. Cortical EEG, electromyography (EMG), and locomotion were recorded telemetrically for 10 days, following an acute dose, from rats receiving vortioxetine-infused chow or paroxetine-infused water and respective controls. Sleep stages were manually scored into active wake, quiet wake, and non-REM or REM sleep. Acute paroxetine or vortioxetine delayed REM onset latency (ROL) and decreased REM episodes. After repeated administration, vortioxetine yielded normal sleep-wake rhythms while paroxetine continued to suppress REM. Paroxetine, unlike vortioxetine, increased transitions from non-REM to wake, suggesting fragmented sleep. Next, we investigated the role of 5-HT3 receptors in eliciting these differences. The 5-HT3 receptor antagonist ondansetron significantly reduced paroxetine's acute effects on ROL, while the 5-HT3 receptor agonist SR57227A significantly increased vortioxetine's acute effect on ROL. Overall, our data are consistent with the clinical findings that vortioxetine impacts REM sleep differently than paroxetine, and suggests a role for 5-HT3 receptor antagonism in mitigating these differences. [ABSTRACT FROM AUTHOR]

Copyright of Acta Psychiatrica Belgica is the property of Acta Psychiatrica Belgica SRMMB and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose – A pragmatic evaluation of the practicality of diabetes screening for users of serotonin specific reuptake inhibitors (SSRI’s). The paper aims to discuss this issue. Design/methodology/approach – This study audited the response of SSRI-users to personal invitation for diabetes screening. One-third of such patients had been screened during the past year. The remaining 217 patients were invited for fasting blood glucose tests and the improvement in screening rates measured. The rate of positive results was compared to a cohort who received fasting blood glucose screening due to physical risk factors for diabetes. Findings – Specific invitation increased the take-up of screening from 34 to 52 per cent of SSRI-users. Engagement was significantly better when patients could be contacted by telephone rather than letter. The SSRI-using cohort had a greater rate of identified diabetes than a cohort with physical risk factors for diabetes. Practical implications – SSRI-users are a difficult group to engage in medical screening and an assertive approach is of value. It is likely that the physical care of these patients would be enhanced by the active maintenance of contact by a practice healthcare professional. Screening of SSRI-users for diabetes is justified by both detection rate and the importance of establishing co-morbidity in terms of treatment decisions. Originality/value – Co-morbidity of diabetes and depression has been observed to result in a poor prognosis for the patient which can be tempered if successful engagement leads to early treatment of both conditions with a more tailored choice of medication and care. [ABSTRACT FROM AUTHOR]

Based on a realist conceptualization of interests, this paper explores how commercial and scientific priorities appear to have converged and diverged during the development of the antidepressant Zelmid. The drug represents the first of the selective serotonin reuptake inhibitors (SSRIs) to reach the market. Zelmid was synthesized in 1971 and launched by the Swedish firm Astra in 1982, but subsequently withdrawn the next year because of adverse neurological effects. This paper draws on in-depth interviews with scientists representing both industry and academia who had high-level involvement in various phases of the project (experimental, pre-clinical and clinical), as well as on textual sources such as scientific articles and memoirs. Zelmid was a product of mechanism-based or “rational” drug discovery from the early 1960s and the associated intermingling of science and commerce. It is argued that both scientists and the pharmaceutical company shared an interest in embracing mechanism-based drug discovery because it simultaneously promised medico-scientific advances and profits. However, the intermingling of science and commerce also strained the relationship between scientific and commercial priorities further along the trajectory of the drug; for example, concerning issues such as dosage strategy and drug use in primary care, where corporate management allegedly took decisions contrary to the recommendations of both academic and company scientists. On such occasions the asymmetry in power became apparent in scientists' narratives: commercial considerations trumped those of science since, ultimately, decisions rest with management, not with scientists. In addition, temporality appears to be associated with the divergence of commercial and scientific priorities. While rare during experimental and pre-clinical phases, divergence was concentrated downstream to the clinical testing and post-marketing phases. It is hypothesized that a similar pattern of convergence and divergence of commercial and scientific priorities may exist in the trajectory of other drugs. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors' (SSRIs') wide use, combined with the blurry limit between health and psychological illness, have led neuroscientists, clinicians and ethicists to envision the possibility of these medications' use in non-clinical populations. This prospect has evoked ethical debates, which have often ignored the findings of the empirical literature. In this context, an evaluation of the empirical evidence for SSRIs' personality enhancing effects is needed. The present paper examines SSRIs' effects on healthy personality, including the Five Factor Model traits Neuroticism and Extraversion, as well as some of their facets: Angry Hostility, Impulsiveness, Vulnerability, Warmth, Gregariousness and Assertiveness. The review encompasses investigations in healthy humans, human clinical populations, as well as relevant animal studies. Emerging data raise the possibility that SSRIs, when used by people without a currently diagnosable mental disorder, may reduce some facets of Neuroticism, especially Angry Hostility. On the other hand, very limited support exists for an SSRI-driven change in other Neuroticism facets, such as Impulsiveness, in healthy humans. An increase in Extraversion (potentially, Warmth, Gregariousness, and, in some contexts, Assertiveness) is possible, but currently available evidence is only indirect. Future research is needed, both to clarify methodological ambiguities in existing studies, and to answer unaddressed questions, such as ones of the stability, predictors, moderators, dose- and context-dependency of the effects. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is one of the most disabling diseases worldwide and is becoming a significant public health threat. Current treatments forMDDprimarily consist of monoamine-targeting agents and have limited efficacy. However, the glutamate neurotransmitter system has recently come into focus as a promising alternative for novel antidepressant treatments. We review the current data on the glutamate NMDA receptor antagonist ketamine, which has been shown in clinical trials to act as a rapid antidepressant inMDD.We also examine ketamine efficacy on dimensions of psychopathology, including anhedonia, cognition, and suicidality, consistent with theNIMH Research Domain Criteria initiative. Other aspects of ketamine reviewed in this paper include safety and efficacy, different administration methods, and the risks of misuse of ketamine outside of medical settings. Finally, we conclude with a discussion of glutamatergic agents other than ketamine currently being tested as novel antidepressants. [ABSTRACT FROM AUTHOR]

The main objective of this paper is to establish the potency range and the action mechanism of selective serotonin reuptake inhibition (SSRI) fluoxetine on female CD-1 mice (25-39 kg). Our results indicated that fluoxetine's antidepressant doses of 16 mg/kg (i.p.), 32 mg/kg (i.p.), and 64 mg/kg (i.p.) had an analgesic and anxiolytic effect without significant results on the spatial memory test. Reduced activity on memory work on specific activities was only observed with a dose of 64 mg/kg (i.p.). This is evidence to suggest that fluoxetine can be more effective with doses that showed an antidepressant effect. It also indicates that fluoxetine can have an analgesic and anxiolytic effect without reducing motor activity on mice. The maximum dose tested on this study showed variations on motor activity of mice suggesting that SSRI fluoxetine can have sedative effects. [ABSTRACT FROM AUTHOR]

Background: Depressive disorders are significantly more common in the medically ill compared to the general population. Depression is associated with worsening of physical symptoms, greater healthcare utilization and poorer treatment adherence. The present paper provides a critical review on the assessment and management of depression in the medically ill. Methods: Relevant articles pertaining to depression in the medically ill were identified, reviewed and synthesized qualitatively. A systematic review was not performed due to the large breadth of this topic, making a meaningful summary of all published and unpublished studies not feasible. Notable studies were reviewed and synthesized by a diverse set of experts to provide a balanced summary. Results: Depression is frequently under-recognized in medical settings. Differential diagnoses include delirium, personality disorders and depressive disorders secondary to substances, medications or another medical condition. Depressive symptoms in the context of an adjustment disorder should be initially managed by supportive psychological approaches. Once a mild to moderate major depressive episode is identified, a stepped care approach should be implemented, starting with general psychoeducation, psychosocial interventions and ongoing monitoring. For moderate to severe symptoms, or mild symptoms that are not responding to low-intensity interventions, the use of antidepressants or higher intensity psychotherapeutic interventions should be considered. Psychotherapeutic interventions have demonstrated benefits with small to moderate effect sizes. Antidepressant medications have also demonstrated benefits with moderate effect sizes; however, special caution is needed in evaluating side effects, drug–drug interactions as well as dose adjustments due to impairment in hepatic metabolism and/or renal clearance. Novel interventions for the treatment of depression and other illness-related psychological symptoms (e.g. death anxiety, loss of dignity) are under investigation. Limitations: Non-systematic review of the literature. Conclusion: Replicated evidence has demonstrated a bidirectional interaction between depression and medical illness. Screening and stepped care using pharmacological and non-pharmacological interventions is merited. [ABSTRACT FROM AUTHOR]

Depression and depressive symptoms are prevalent in patients with cancer. Depression is underdiagnosed and therefore, patients often receive inadequate treatment for depression. We have assessed the evidence of primary prophylactic treatment for depression in patients with cancer. The systematic review was prospectively registered at PROSPERO and was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Five electronic databases were searched on the 31st of May 2018 and two independent reviewers screened the papers. Randomized controlled trials of adult patients with cancer treated prophylactically with an antidepressive intervention of any kind using validated assessment tools to measure depression or depressive symptoms were included. No language or publication year restrictions were applied. Seven out of eighteen studies reported a statistically significant prophylactic effect on depression. The studies were classified into three groups based on the type of intervention. The meta-analyses showed a significant difference in favour of pharmacotherapy (RR 0.34, 95% CI 0.18; 0.63), psychotherapy (SMD -0.23,95% CI -0.46; 0.00), and other interventions (SMD -0.17, 95% CI -0.31; −0.03). Only one study had overall low risk of bias and the rest had high risk of bias predominantly due to blinding, incomplete data, or allocation concealment. Preventive measures have been examined in patients with cancer, but no convincing evidence for any specific intervention is present. Depression in patients with cancer can be prevented and prophylactic treatment should be given during oncological treatment but further high quality studies testing safe interventions are still needed. [ABSTRACT FROM AUTHOR]