Classes Of Antidepressants Research Articles

Antidepressants versus placebo for generalised anxiety disorder (GAD).

Generalised anxiety disorder (GAD) is a mental health condition characterised by excessive anxiety and worry about everyday events. GAD is a common disorder and generally affects women twice as often as men. Treatments include various psychological and pharmacological therapies. Among the pharmacological therapies, antidepressants, in particular, selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs), are commonly used for the treatment of GAD and many studies have shown their benefit over placebo. Only one systematic review and meta-analysis comparing all antidepressants to placebo has been done in the past. Since then, new data on existing antidepressants have emerged and new antidepressants have been introduced. An updated and more comprehensive review is needed to provide a stronger understanding of the efficacy, acceptability, tolerability, and impact on the quality of life of the various types of antidepressants compared to placebo. To assess the effects of antidepressants in GAD in adults, specifically: to determine the efficacy of antidepressants in alleviating symptoms of GAD compared to placebo and to review the acceptability of antidepressants in GAD in terms of adverse effects, including the general prevalence of adverse effects compared to placebo. We searched the Cochrane Common Mental Health Disorders (CCMD) register, CENTRAL, MEDLINE, Embase, PsycINFO, and two trials registers in October 2022. We included randomised controlled trials (RCT) or cluster-RCTs that randomly assigned participants to receive either an antidepressant or placebo for the treatment of GAD. There were no restrictions on dose, frequency, intensity, or duration of treatment. The studies included adults of either sex with a primary diagnosis of GAD and without any serious medical comorbidities. Psychiatric comorbidities were allowed as long as GAD was the primary diagnosis. We excluded studies investigating psychotherapies and those that included participants who had regular use of benzodiazepines. There were no restrictions on setting, country, or language. Two review authors independently checked eligibility and extracted data following standard Cochrane methodological procedures. We assessed risk of bias using the Cochrane RoB 1 tool. A third review author resolved disagreements between the two primary review authors. We extracted study characteristics, participant characteristics, intervention details, settings, and outcome measures regarding efficacy, acceptability, tolerability, and quality of life. We used GRADE to assess the certainty of the evidence. We included 37 unique RCTs with 12,226 participants in the review. The studies included adults with moderate-severe GAD and without any serious medical comorbidities. Few studies included participants with secondary psychiatric comorbidities. The double-blind treatment duration ranged from four weeks to 28 weeks. Antidepressants have a benefit over placebo on rate of treatment response measured as a reduction of at least 50% on the Hamilton Anxiety Rating Scale (HAM-A) (risk ratio (RR) 1.41, 95% confidence interval (CI) 1.29 to 1.55; 20 studies, 7267 participants; high-certainty evidence). The magnitude of effect corresponds to a number needed to treat for an additional beneficial outcome (NNTB) of 7 (95% CI 5 to 9). Antidepressants have no difference in acceptability compared to placebo, measured as the number of participants who dropped out during the trial as a proportion of the total number of randomised participants (RR 1.03, 95% CI 0.93 to 1.14; 33 studies, 11,294 participants; high-certainty evidence). Fewer participants dropped out due to a lack of efficacy in the antidepressant group compared to the placebo group (RR 0.41, 95% CI 0.33 to 0.50; 29 studies, 11,007 participants; high-certainty evidence) with an NNTB of 27 (95% CI 24 to 32), and more participants dropped out due to adverse effects in the antidepressant group compared to placebo (RR 2.18, 95% CI 1.81 to 2.61; 32 studies, 11,793 participants; high-certainty evidence) with a number needed to treat for an additional harmful outcome (NNTH) of 17 (95% CI 13 to 112). We observed similar findings when classes of antidepressants were compared with placebo. The certainty of the evidence for the analyses comparing different classes of antidepressants to placebo was high. This review added to the growing literature on antidepressants in the treatment of GAD. We have high confidence that antidepressants are more effective than placebo at improving treatment response and that antidepressants have similar acceptability to placebo. Fewer participants dropped out due to a lack of efficacy in the antidepressant group compared to the placebo group and more participants dropped out due to adverse effects in the antidepressant group compared to placebo. We are highly confident in this evidence. This review identified some important gaps in the literature on antidepressants for GAD and can be used as a tool to guide future research. Future studies may be more transparent with their methodology and outcome reporting. Future reviews may also include people with comorbidities, and explore other sources of heterogeneity.

An Exploration of the Interplay Between Caffeine and Antidepressants Through the Lens of Pharmacokinetics and Pharmacodynamics.

Caffeine consumption is regarded as a widespread phenomenon, and its usage has continued to increase. In addition, the growing usage of antidepressants worldwide and increase in mental health disorders were shown in recent statistical analyses conducted by the World Health Organisation. The coadministration of caffeine and antidepressants remains a concern due to potential interactions that can alter a patient's response to therapy. This review investigates the pharmacokinetic and pharmacodynamic interactions between caffeine and the five main classes of antidepressants: selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), and other antidepressants not categorised by class, which we have categorised as 'miscellaneous'. The interaction between fluvoxamine and caffeine resulted in increased concentrations of caffeine in the body and lowered the renal clearance of fluvoxamine. Other SSRIs such as fluoxetine and escitalopram had augmented antidepressant effects by decreasing their renal clearance and prolonging their effects in the body when coadministered with caffeine. Caffeine may also increase the concentration of paroxetine, potentially affecting its pharmacodynamic effects. TCAs such as clomipramine, imipramine, desipramine, and sertraline, were found to reduce the metabolism of caffeine. However, studies suggest caffeine had no significant effect on the concentration of these medications in blood or brain tissue. The inhibition of caffeine at high doses when used with MAOIs such as tranylcypromine and phenelzine was found to lead to a higher likelihood of experiencing hypertension. Coadministration of caffeine with venlafaxine (SNRIs) suggests minimal interactions between the two substances and the pharmacodynamic effects of venlafaxine were unlikely to be impacted by caffeine consumption. Miscellaneous antidepressants (reboxetine, mianserin, agomelatine, maprotiline, and mirtazapine) displayed varying pharmacodynamic interactions with caffeine, resulting in increased antidepressant effects where vortioxetine, maprotiline, and mirtazapine failed to demonstrate any interactions. In conclusion, caffeine demonstrated varying effects on the pharmacokinetic and pharmacodynamic properties of each class of antidepressants, with several classes of antidepressants demonstrating a similar effect on caffeine.

A Scoping Review of Eosinophilic Pneumonia and Antidepressants: An Association Not to Be Overlooked.

Background: Eosinophilic pneumonias denote a rare condition, wherein infiltrating eosinophilic granulocytes accumulate within the lung parenchyma. Although eosinophilic pneumonias may be idiopathic, they are also associated with secondary causes. More than 110 medications have been linked to eosinophilic pneumonia, including several antidepressants. This review presents an analysis of case reports of eosinophilic pneumonia correlated to antidepressants. Objectives: The objectives of this study are to provide a contemporary overview of the literature delineating eosinophilic pneumonia as a potential sequela of antidepressant medication treatment, and to discuss possible pathogenetic mechanisms linking antidepressants to eosinophilic pneumonia. Methods and Data Selection: A literature search was performed in PubMed and Scopus databases from 1963 to October 2024. The search strategy used the terms "eosinophilic pneumonia AND antidepressants". Sources included in this review were screened for relevance, focusing on references discussing eosinophilic pneumonia associated with any class of antidepressants. Case reports meeting the diagnostic criteria for acute eosinophilic pneumonia (AEP) or chronic eosinophilic pneumonia (CEP) were included in the review. Clinical, epidemiological, laboratory, radiology and bronchoscopy data, implicated antidepressant and dosage, and therapeutic interventions were reported. Results: This study found that various types of antidepressants are associated with AEP and CEP. The clinical presentation ranges from mild symptoms to respiratory failure and intubation. Outcomes were favorable in most cases, with complete remission achieved after discontinuation of the causative drug and, in severe cases, a short course of corticosteroids. Conclusions: Although a rare cause, antidepressants may lead to eosinophilic pneumonia, and should be considered in the differential diagnosis of unexplained pulmonary infiltrates. Clinical suspicion must be aroused, as early recognition would prevent unnecessary work-up and navigation of the diagnosis.

Modern Experience in Pharmacotherapy of Irritable Bowel Syndrome in Children

This review examines modern approaches to the diagnosis and treatment of irritable bowel syndrome (IBS) in children, one of the most common functional disorders of the gastrointestinal tract. IBS is characterized by chronic abdominal pain, intestinal motility disorders and stool changes, which significantly reduces the quality of life of patients. The article analyzes in detail the pathogenetic mechanisms of IBS, including the role of the gut–brain axis, gut microbiota and neuroendocrine factors. Special attention is paid to the pharmacotherapy of IBS in children, including the use of antidepressants, probiotics and herbal components, as well as the role of correctors of the motor activity of the digestive tract in relieving symptoms. Modern recommendations on the use of various classes of antidepressants are considered, taking into account their pharmacokinetic and pharmacodynamic characteristics. The prospects of using probiotics and herbal preparations in the complex therapy of IBS are also analyzed. The data obtained confirm the need for a personalized approach to the treatment of IBS, taking into account the genetic and physiological characteristics of patients.

Inclination of antidepressant medication continuation during pregnancy between 2012 and 2023 in Japan: A cohort study.

As multiple Japanese academic societies have recently issued treatment guidelines for perinatal antidepressant treatments, it is considered worthwhile to evaluate the latest trends and continuation of antidepressant medication during pregnancy to optimize antenatal prescriptions. The prevalence, trend, and continuation of antidepressant use during pregnancy in Japan from 2012 to 2023 were evaluated, using a large administrative claims database, in women whose pregnancies ended in live births. Annual changes were evaluated using a multivariate logistic regression model adjusted for maternal age at delivery. Of 179,797 women with a mean maternal age at delivery of 32.5 years, 1870 (1.04 %) were prescribed antidepressants during pregnancy. The prevalence significantly increased (P < 0.0001) from 0.63 % in 2012 to 1.67 % in 2023. Antidepressants were prescribed to 1730 women (0.96 %) during the first trimester. Of these, 670 (38.7 %) were antidepressant continuers throughout pregnancy, showing a significant increase (P < 0.0001) from 19.51 % in 2012 to 50.70 % in 2023. The most frequently prescribed class of antidepressants during pregnancy was serotonin reuptake inhibitors (0.74 %), especially sertraline (0.33 %) and escitalopram (0.23 %), with a significant increase in their annual prevalence. Prescriptions for women whose pregnancies ended in abortion or stillbirth could not be evaluated. Given that antidepressant use and its continuation during pregnancy have become more common, it is important to further disseminate knowledge of the guidelines to healthcare professionals and women of childbearing age, including the promotion of preconception care and shared decision-making.

Investigating the role of GPR39 in treatment of stress-induced depression and anxiety.

Chronic stress is one of the leading causes of depression. Yet, knowledge of the pathomechanism of this process still eludes us. Chronic unpredictable mild stress (CUMS) model of depression enables researchers to look for a root cause of the disease in mice by mimicking a stressful human environment. Since zinc has already been shown to impact the treatment of depression, in our study we aimed to shed light on the role of the zinc receptor GPR39 in stress-induced depression. We also aimed to highlight the role of GPR39 activation in monoamine-based antidepressant treatment. Using large battery of behavioural tests, we provided a detailed description of CUMS-induced phenotype in both - CD-1 and GPR39 knock-out mice. Our experiments showed that combined treatment with TC-G 1008 (GPR39 agonist) and antidepressants produces stronger antidepressant-like effect of classic antidepressants. We also demonstrated the inter-strain differences in stress response and the greater stress susceptibility of GPR39 knock-out mice. The lack of GPR39 expression also either diminished or completely abolished the response to treatment with different antidepressants combined with TC-G 1008. The results show that GPR39 KO mice are more susceptible to chronic stress and that they are non-responsive to SSRI treatment. Utilizing various behavioural tests gave us much broader understanding not only of the role of GPR39 in depression treatment, but also of the importance of detailed behavioural description in a proper interpretation of the results. Further research with known selective agonists and antagonists of GPR39 will be necessary to understand the full potential of this receptor as a pharmacological target.

Antidepressants and Weight Gain: An Update on the Evidence and Clinical Implications.

To highlight recent research on antidepressant use and weight change and explore best clinical practices for reducing weight gain and obesity risk in individuals with depression. Research on antidepressant use and weight gain suggests that genetic and biological factors including metabolizer phenotypes and inflammation can help to predict an individual's threshold for weight change among specific agents. For individuals with increased susceptibility to metabolic complications, medications including bupropion, fluoxetine, and newer agents (e.g., gepirone) have shown to be efficacious in improving depressive symptoms while concurrently reducing metabolic risks. Additional areas of focus following antidepressant related weight gain include switching to a weight neutral drug alternative, integrated behavioral interventions, and/or pharmacotherapy including GLP-1 receptor agonists (e.g., metformin, liraglutide). Individuals experiencing depression are at heightened risk of metabolic disorders and weight gain, which may be further exacerbated by antidepressant treatment. The increased support of weight neutral antidepressant agents in addition to innovative lifestyle interventions, breakthroughs in drug mechanisms, anti-obesity medications and overall familiarity with the side effects of each antidepressant class will help clinicians make appropriate decisions when treating patients with depression.

Emerging role of microglia in the developing dopaminergic system: perturbation by early life stress.

Early life stress correlates with a higher prevalence of neurological disorders, including autism, attention-deficit/hyperactivity disorder, schizophrenia, depression, and Parkinson's disease. These conditions, primarily involving abnormal development and damage of the dopaminergic system, pose significant public health challenges. Microglia, as the primary immune cells in the brain, are crucial in regulating neuronal circuit development and survival. From the embryonic stage to adulthood, microglia exhibit stage-specific gene expression profiles, transcriptome characteristics, and functional phenotypes, enhancing the susceptibility to early life stress. However, the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood. This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia, leading to dopaminergic system disorders, along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions. Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support (e.g., insulin-like growth factor-1) and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning. Furthermore, blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission. Furthermore, inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons, inhibiting dopamine synthesis, reuptake, and receptor activity. Enhanced microglial phagocytosis inhibits dopamine axon extension. These long-lasting effects of microglial perturbations may be driven by early life stress-induced epigenetic reprogramming of microglia. Indirectly, early life stress may influence microglial function through various pathways, such as astrocytic activation, the hypothalamic-pituitary-adrenal axis, the gut-brain axis, and maternal immune signaling. Finally, various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed. These strategies include classical antidepressants and antipsychotics, antibiotics and anti-inflammatory agents, and herbal-derived medicine. Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.

Antidepressant use and dementia risk

Use of antidepressants in elderly patients has raised concerns over the risk of impaired cognition and development of dementia. The research data evaluating this potential association are conflicting, however, with little information on the effects of long‐term exposure or potential differences among the various classes of antidepressants (Wang et al., 2018).

Impact of Antidepressant Use on Intraoperative Blood Loss and Transfusion Rates in Lumbar Fusion Surgery

A quarter of spine surgery patients take antidepressants. Basic science research has suggested serotonergic antidepressants impair platelet function. This has been supported by only a small number of works in the setting of spine surgery. The purpose of this study is to investigate the impact of antidepressants on intraoperative bleeding risk during lumbar fusion. Patients who underwent elective 1-3 level lumbar fusion at a single, academic, tertiary center (2017-2021) were identified. Antidepressant use and class, demographic and surgical data were evaluated. Bleeding risk was assessed by total intraoperative blood loss (mL), calculated using the formula by Gross et al, and by postoperative transfusion. Patients prescribed versus not prescribed an antidepressant were matched 1:1 by age, sex, BMI, Elixhauser, smoking status, and levels fused. Appropriate statistical analysis was performed (Alpha was set at 0.05). 420 patients with, and 420 patients without an antidepressant prescription at the time of lumbar fusion were identified. Patients without an antidepressant prescription had a higher Charlson Comorbidity Index (0.91 ± 1.09 vs. 0.76 ± 1.1; p = 0.048), but otherwise the groups were demographically similar, and underwent similar surgeries. Antidepressant use was not associated with increased intraoperative bleeding or postoperative transfusion rate, regardless of sub-analysis by procedure type or antidepressant class. Antidepressant use was not associated with increased intraoperative blood loss or increased postoperative transfusion requirement, regardless of sub-analysis by fusion type or antidepressant class. The current findings do not support discontinuing antidepressants prior to lumbar fusion.

A novel hypothesis-generating computational workflow utilizing reverse pharmacophore mapping-A drug repurposing perspective of istradefylline towards major depressive disorder.

Drug repurposing (DR) offers a compelling alternative to traditional drug discovery's lengthy, resource-intensive process. DR is the process of identifying alternative clinical applications for pre-approved drugs as a low-risk and low-cost strategy. Computational approaches are crucial during the early hypothesis-generating stage of DR. However, 'large-scale' data retrieval remains a significant challenge. A computational workflow addressing such limitations might improve hypothesis generation, ultimately benefit patients and advance DR research. We introduce a novel computational workflow (combining free-accessible computational platforms) to provide 'proof-of-concept' of the pre-approved drug's suitability for repurposing. Three key phases are included: target fishing (via reverse pharmacophore mapping), target identification (via disease- and drug-target pathway identification) and retrospective literature and drug-like analysis (via in silico ADMET properties determination). Istradefylline is a Parkinson's disease-approved drug with literature-attributed antidepressant properties remaining unclear. Practically applied, istradefylline's antidepressant activity was assessed in the context of major depressive disorder (MDD). Data mining aided by target identification resulted in istradefylline potentially representing a novel antidepressant drug class. Retrieved drug targets (KYNU, MAO-B, ALOX12 and PLCB2) associated with selected MDD pathways (tryptophan metabolism and serotonergic synapse) generated a hypothesis that istradefylline increased extracellular 5-HT levels (MAO-B inhibition) and reduced inflammation (KYNU, ALOX12 and PLCB2 inhibition). The practically applied workflow's generated hypothesis aligns with known experimental data, validating the effectiveness of this novel computational workflow. It is a low-risk and low-cost DR computational tool providing a bird's-eye view for exploring alternative clinical applications of pre-approved drugs.

Spectrophotometric Analysis of Edible Salt for Iodate Quantities

Introduction: The Spectrophotometric method was used to identify iodate by utilizing a class of antidepressants known as imipramine hydrochloride (IPH), desipramine hydrochloride (DPH), clomipramine hydrochloride (CPH), and trimipramine hydrochloride (TPM). Method: Iodate in nano amounts can be measured using this method in an acidic medium with 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate (MBTH) acting as an electrophilic coupling reagent. The MBTH-IPH/DPH/CPH/TPM method had a blue with a maximum absorbance at 630 nm. Beer, 's law was followed, and the blue color that was produced remained stable for up to 24 hours at room temperature (270C). Result: The boundaries depending on the situation for the assessment of the strategy like molar absorptivity and Sandell's sensitivity gave various qualities with various reagents. The method was tested with interference from common 11 cations and 8 anions, and the results obtained were within a reasonable range. Conclusion: The procedure was used for the determination of iodate in iodized edible salts because iodate is one of the common ions in iodized salt. It was found that the method is reliable and can be used effectively for the determination. result: The methods obey Beer’s law. The colour developed was stable for 24 hours at room temperature. The molar absorptivity and Sandell’s sensitivity gave different values with different reagents. Interference was not observed with 11 cations and 8 anions. The method showed good reproducibility and can be satisfactorily applied for the determination in iodate in iodized edible salts.

Prevalence of Antidepressant Prescriptions for Community-Dwelling Adults Diagnosed with Depressive Disorder in the UK: A Systematic Review.

The UK National Institute for Health and Care Excellence (NICE) guidance for the treatment of depression is widely followed and has international influence. According to these guidelines, antidepressant medications are recommended for moderate to severe depression. Nonetheless, antidepressants are increasingly prescribed, including for cases of subthreshold and mild depression. This may indicate that a proportion of depressed patients uses pharmacological interventions with unclear evidence-base, though other factors such as physical and mental health comorbidities need to be accounted for. This study aims to investigate the prevalence and trends of antidepressant prescriptions among community-dwelling adults diagnosed with depression according to NICE recommendations. We conducted a systematic review of PsycInfo, PubMed/MEDLINE, and Scopus databases. Observational studies reporting on the prevalence of antidepressant treatments in UK adults diagnosed with depression were sought. Fifteen studies were included. The prevalence of antidepressants for depression treatment ranged from 30.8 to 95% and mainly concerned selective serotonin reuptake inhibitors (SSRIs) among classes of antidepressant drugs. Little information about depression severity as well as comorbid conditions was reported. High prevalence rates of antidepressant drug use highlight the widespread adoption of pharmacological interventions, while also raising concerns about compliance with NICE guidelines. Careful assessment of depressive illness severity and comorbidities is needed to ensure the delivery of adequate care to people with depression. Systematic Review Registration Number (PROSPERO) CRD42023448152.

Classical psychedelics’ action on brain monoaminergic systems

The study of the mechanism of action of classical psychedelics has gained significant interest due to their clinical potential in the treatment of several psychiatric conditions, including major depressive and anxiety disorders. These drugs bind 5-hydroxytryptamine receptors (5-HTR) including 5-HT1AR, 5-HT2AR, 5-HT2BR, and/or 5-HT2CR, as well as other targets. 5-HTRs regulate the activity of ascending monoaminergic neurons, a mechanism primarily involved in the action of classical antidepressant drugs, antipsychotics, and drugs of abuse. Sparse neurochemical data have been produced on the control of monoaminergic neuron activity in response to classical psychedelics. Here we review the available data in order to determine whether classical psychedelics have specific neurochemical effects on serotonergic, dopaminergic, and noradrenergic neurons. The data show that these drugs have disparate effects on each monoaminergic system, demonstrating a complex response with state-dependent and region-specific effects. For instance, several psychedelics inhibit the firing of serotonergic neurons, although this is not necessarily associated with a decrease in serotonin release in all regions. Noradrenergic neuron spontaneous activity also appears to be inhibited by psychedelics, also not necessarily associated with a decrease in noradrenaline release in all regions. Psychedelics influence on dopaminergic systems is also complex as the above-mentioned 5-HTRs may have opposing effects on dopaminergic neuron activity, in a state-dependent manner. There is an apparent lack of clear neuronal signature induced by psychedelics on monoaminergic neuron activity despite specific recurrent mechanisms. This review provides a current summary of the action of psychedelics on monoamine neuromodulators serotonin, dopamine and noradrenaline, compiling reoccurring and contradictory findings demonstrating that a monoamine signature of psychedelics, if applicable, would be state- and region-dependant.

The 3 Ds: Depression, Dysbiosis, and Clostridiodes difficile.

This paper explores the intricate relationship between depression, gut dysbiosis, and Clostridioides difficile infections, collectively termed "The 3 Ds". Depression is a widespread mental disorder increasing in prevalence. It is recognized for its societal burden and complex pathophysiology, encompassing genetic, environmental, and microbiome-related factors. The consequent increased use of antidepressants has led to growing concerns about their effects on the gut microbiome. Various classes of antidepressants and antipsychotics show antimicrobial activity, potentially leading to shifts in the gut microbiome and contributing to the development of dysbiosis. Dysbiosis, in turn, can predispose individuals to opportunistic infections like C. difficile, a significant healthcare concern due to its high recurrence rates and severe impact on patients' quality of life. Further, the link between antidepressant use and an increased risk of C. difficile infection (CDI) is explored and, finally, the emergence of live biotherapeutic products as novel treatment options for recurrent CDI is discussed.

Psychotropic medication profiles and future treatment risk among Northern Irish adults: a Latent Transition Analysis

ObjectiveTo identify within the Northern Irish adult population distinct psychotropic prescription profiles at initiation/discontinuation of a ‘treatment episode’ and associated risk of future psychotropic treatment. ApproachData linkage analysis of psychotropic prescriptions and household information. The ‘treatment episode’ was defined as the first identified period (&gt;6 months) of psychotropic prescriptions preceded and followed by ≥ 12 months without psychotropics. Latent Transition Analysis was used to identify classes of psychotropic usage at initiation/discontinuation of treatment, with Cox regression used to estimate the likelihood of recommencing psychotropics. ResultsWe identified 157,836 patients, median age forty-five years (IQR 32,62) , 58.7% female, median exposure 1.5 years (IQR 1,2.5). Five latent classes of patients were identified in relation to received prescriptions: hypnotics, anxiolytics, antipsychotics, antidepressants and multiple psychotropics. The percentage of patients in the antidepressant class increased between initiation and discontinuation (from 64.2% to 67.1%) while that in the multiple psychotropics class fell (from 7.2% to 5.4%). 43% of patients who started treatment with multiple psychotropics had switched to antidepressants at discontinuation. These patients were significantly less likely to restart treatment than those who continued to receive multiple psychotropics (Hazard Ratio 0.83, 95%CI 0.76, 0.89) after adjusting for age at discontinuation, year of entry, deprivation, sex and duration of previous treatment. ConclusionsContinued receipt of multiple psychotropics is associated with an increased risk of future/ongoing treatment. This may reflect diagnostic uncertainly, complex disorder and discontinuation-associated side-effects. ImplicationsResearchers and practitioners alike should consider the diagnostic, health and treatment implications of these findings.

Increased Odds of Cognitive Impairment in Adults with Depressive Symptoms and Antidepressant Use.

The relationship between antidepressant use and class with cognition in depression is unclear. This study aimed to evaluate the association of cognition with depressive symptoms and antidepressant use (class, duration, number). Data from the National Health and Nutrition Examination Survey were examined for cognitive function through various tests and memory issues through the Medical Conditions questionnaire. Depressive symptoms were assessed using the Patient Health Questionnaire-9. A total of 2867 participants were included. Participants with depressive symptoms had significantly higher odds of cognitive impairment (CI) on the animal fluency test (aOR=1.89, 95% CI=1.30, 2.73, P=0.002) and Digit Symbol Substitution test (aOR=2.58, 95% CI=1.34, 4.9, P=0.007), as well as subjective memory issues (aOR=7.25, 95% CI=4.26, 12.32, P<0.001) than those without depression. There were no statistically significant associations between any of the CI categories and depressive symptoms treated with an antidepressant and antidepressant use duration. Participants who were using more than one antidepressant had significantly higher odds of subjective memory issues than those who were using one antidepressant. Specifically, users of atypical antidepressants, selective serotonin reuptake inhibitors, or tricyclic antidepressants (TCAs) had significantly higher odds of subjective memory issues in comparison to no antidepressants, with TCAs showing the largest odds (aOR=4.21, 95% CI=1.19, 14.86, P=0.028). This study highlights the relationship between depressive symptoms, antidepressant use, and CI. Future studies should further evaluate the mechanism underlying this phenomenon.

Fast-acting antidepressant-like effects of ketamine in aged male rats

BackgroundThe aging process causes anatomical and physiological changes that predispose to the development of late-life depression while reduces the efficacy of classical antidepressants. Novel fast-acting antidepressants such as ketamine might be good candidates to be explored in the context of aging, especially given the lack of previous research on its efficacy for this age period. Thus, the aim of the present study was to characterize ketamine’s effects in older rats.MethodsThe fast-acting (30 min) and repeated (7 days) antidepressant-like effects of ketamine (5 mg/kg, ip) were evaluated in 14-month-old single-housed rats through the forced-swim and novelty-suppressed feeding tests. In parallel, the modulation of neurotrophic-related proteins (i.e., mBDNF, mTOR, GSK3) was assessed in brain regions affected by the aging process, prefrontal cortex and hippocampus, as well as possible changes in hippocampal cell proliferation.ResultsAcute ketamine induced a fast-acting antidepressant-like response in male aged rats, as observed by a reduced immobility in the forced-swim test, in parallel with a region-specific increase in mBDNF protein content in prefrontal cortex. However, repeated ketamine failed to induce antidepressant-like efficacy, but decreased mBDNF protein content in prefrontal cortex. The rate of hippocampal cell proliferation and/or other markers evaluated was not modulated by either paradigm of ketamine.ConclusionsThese results complement prior data supporting a fast-acting antidepressant-like effect of ketamine in rats, to further extend its efficacy to older ages. Future studies are needed to further clarify the lack of response after the repeated treatment as well as its potential adverse effects in aging.

Antidepressant class and concurrent rTMS outcomes in major depressive disorder: a systematic review and meta-analysis

Repetitive transcranial magnetic stimulation (rTMS) is frequently used as an adjunctive treatment with antidepressants for depression. We aimed to evaluate the clinical efficacy and safety of antidepressant classes when administered concurrently with rTMS for the management of major depressive disorder (MDD). In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from inception to April 12th 2024 for terms relating to medication, depression, and rTMS and appraised by 2 independent screeners. All randomized clinical trials that prospectively evaluated a specific antidepressant adjunctively with sham rTMS as a control in MDD were included. The study was registered with PROSPERO (CRD42023418435). The primary outcome measure assessed symptomatic improvement measured by formal depression scales. We used a random-effects model with pooled Standardized Mean Differences (SMDs) and log odds ratios (OR). All studies were assessed for their methodological quality and bias using the Cochrane Collaboration Risk of Bias tool version 2 (RoB2). 14 articles from 5376 identified studies were included in the systematic review and meta-analysis. There was only sufficient trial data to evaluate the effects of rTMS and combination therapy with selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs). Across studies, 848 participants (mean [SD] age:41.1 [18.7] years for SSRIs, 51.8 [3.8] years for SNRIs) prospectively examined the efficacy of antidepressant medication with rTMS. Combining rTMS with SSRIs led to significantly lower depression scores, (SMD [CI] of-0.65 [-0.98,-0.31], p=0.0002, I2=66.1%), higher response (OR=0.97 [0.50, 1.44], p<0.0001, I2=25.33%) and remission rates (OR=1.04 [0.55, 1.52], p<0.0001, I2=0.00%) than medication with sham rTMS. No additive benefit was found for SNRIs with rTMS (SMD of 0.10 [-0.14, 0.34], p=0.42, I2=0.00%; OR=0.12 [-0.39, 0.62], p=0.64, I2=0.00%; OR=-0.31 [-0.90, 0.28], p=0.86, I2=39.9%). The overall risk of bias for the included studies ranged from low to high, with 1 study having a high risk of bias. The combination of rTMS with SSRIs, but not SNRIs, significantly reduced depression severity, increasing response and remission rates. Some analyses demonstrated high heterogeneity, which was influenced by an SSRI trial with a high effect size. Overall, these results suggest that not all antidepressant combination therapies are alike, and SSRIs should be considered when initiating rTMS. Donald T. Stuss Young Investigator Research Innovation Award from the Sandra Black Centre for Brain Resilience & Recovery and the Harquail Centre for Neuromodulation through the Sunnybrook Foundation.

Association between antidepressant use and delirium in older adults: an analysis of the World Health Organization’s global pharmacovigilance database

BackgroundPsychoactive drugs frequently cause delirium adverse events in older adults. However, few data on the relationship between antidepressants and delirium are available. Here, we investigated the association between antidepressant prescription and pharmacovigilance reports of delirium in older adults.MethodsUsing the World Health Organization’s VigiBase® global pharmacovigilance database from 1967 to 2022, we performed a disproportionality analysis in order to probe the putative associations between each antidepressant class (non-selective monoamine reuptake inhibitors (NSMRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), alpha-2-adrenergic receptor antagonists, and other antidepressants) and reports of delirium in people aged 65 or over. We calculated the reporting odds ratios (r-OR) and their 95% confidence interval ([95%CI]) with logistic regression models before and after adjustment for confounding factors. Secondary analyses were performed for each drug and within each class by age group (65-74, and 75 and over). We also studied the reports of concomitant delirium and hyponatremia.ResultsOur main analysis included 87,524 cases of delirium. After adjustment for confounders, a significant association was found between delirium and all antidepressant classes other than SNRIs. Intraclass disparities were found for the association between the most frequently prescribed antidepressants and reports of delirium. An elevated risk of reports of concomitant delirium and hyponatremia was found for SSRIs (4.46 [4.01-4.96]), SNRIs (1.25 [1.07-1.46]), MAOIs (1.72 [1.41-2.09]), and the “other antidepressants” class (1.47 [1.30-1.65]).ConclusionsThere was a significant association between reports of delirium and antidepressant classes (other than SNRIs). However, this association varied from one drug to another within a given antidepressant class. Moreover, this association could not always be explained by antidepressant-induced hyponatremia.