First-line Treatment For Depression Research Articles

Drug-Drug Interactions of Selective Serotonin Reuptake Inhibitors: A Pharmacovigilance Study on Real-World Evidence from the EudraVigilance Database.

As the most common psychiatric symptom, depression represents a subject of high interest for the medical community. Background/Objectives: International guidelines consider selective serotonin reuptake inhibitors (SSRIs) the first-line treatment of depression. Although having better efficacy and tolerability in comparison to tricyclic antidepressants or monoamine oxidase inhibitors, the diversity and potential severity of adverse effects and interactions manifested by SSRIs, combined with the frequency of prescriptions, lead to the necessity of evaluating real-world data. The aim of this study was to identify and evaluate the drug interactions reported in EudraVigilance (EV) for the six SSRIs representatives that are authorized in Europe: fluoxetine (FXT), fluvoxamine (FVM), citalopram (CIT), escitalopram (ESC), paroxetine (PAR) and sertraline (SER). The entire class of SSRIs was examined as a comparator to identify whether one of the representatives was more prone to reporting. Methods: Descriptive analysis and disproportionality analysis were conducted on data extracted from the EV database. Results: A total of 326,450 adverse reactions (ADRs) were reported for the SSRIs group. Approximately a quarter of these (n = 83,201; 25.46%) were reported for SER and 22.37% (n = 73,131) for PAR. Of the total ADRs reported, 2.12% (n = 6925) represent preferred terms related to drug-drug interactions (DDIs): SER (n = 1474; 22.37%), CIT (n = 1272, 19.86), and FXT (n = 1309, 19.83%). Specific ADRs related to inhibitory activity represent 0.98%, and for potentiating activity, 1.89%. Conclusions: Although representing a small value of the total ADRs, DDIs may be related to severe outcomes. Awareness should be raised for this category of ADRs that can be reduced by the joined efforts of physicians and pharmacists.

The neurobiological mechanism underlying ketamine’s rapid-acting antidepressant effect

Depression is one of the most common disabling mental disorders. However, first-line treatments for depression are typically slow-acting. Ketamine, a glutamatergic modulator with rapid antidepressant effects, has proven effective in treating both refractory depression and suicidal tendencies. The neurobiological mechanisms underlying the effects of antidepressants have become a research hotspot; yet, the exact processes remain unclear. Brain imaging studies have provided important evidence from macroscopic perspectives, such as brain structure and function, while biochemical studies have made significant discoveries from microscopic perspectives, including proteomics and genomics. Previous reviews have summarized a broad range of biomarkers related to the ketamine response, encompassing studies in imaging, electrophysiology, metabolism, immunology, genetics, and neurotrophy. In this review, we systematically summarize a number of potential biomarkers for predicting and modulating the efficacy of ketamine, from both macroperspectives (such as neuroimaging and neuroelectrophysiological markers) and microperspectives (such as neurobiochemical and genetic markers). Although research in this area is still in its infancy, these biomarkers can help clinicians identify whether ketamine intervention is needed for treatment-resistant depression, thereby reducing the burden on patients and society. However, the majority of biomarkers are still in the preclinical exploratory stage, and existing findings are limited. To realize the clinical application of these biomarkers, future studies should combine biomarkers of different types to investigate the relationships and interactions between them. This approach aims to optimize clinical outcomes by enhancing the involvement of biological targets in new models.

What predicts response to sertraline for people with depression in primary care? a secondary data analysis of moderators in the PANDA trial.

Antidepressants are a first-line treatment for depression, yet many patients do not respond. There is a need to understand which patients have greater treatment response but there is little research on patient characteristics that moderate the effectiveness of antidepressants. This study examined potential moderators of response to antidepressant treatment. The PANDA trial investigated the clinical effectiveness of sertraline (n = 326) compared with placebo (n = 329) in primary care patients with depressive symptoms. We investigated 11 potential moderators of treatment effect (age, employment, suicidal ideation, marital status, financial difficulty, education, social support, family history of depression, life events, health and past antidepressant use). Using multiple linear regression, we investigated the appropriate interaction term for each of these potential moderators with treatment as allocated. Family history of depression was the only variable with weak evidence of effect modification (p-value for interaction = 0.048), such that those with no family history of depression may have greater benefit from antidepressant treatment. We found no evidence of effect modification (p-value for interactions≥0.29) by any of the other ten variables. Evidence for treatment moderators was extremely limited, supporting an approach of continuing discuss antidepressant treatment with all patients presenting with moderate to severe depressive symptoms.

Psychedelics and sexual functioning: a mixed-methods study

Do psychedelics affect sexual functioning postacutely? Anecdotal and qualitative evidence suggests they do, but this has never been formally tested. While sexual functioning and satisfaction are generally regarded as an important aspect of human wellbeing, sexual dysfunction is a common symptom of mental health disorders. It is also a common side effect of selective serotonin reuptake inhibitors (SSRIs), a first line treatment for depression. The aim of the present paper was to investigate the post-acute effects of psychedelics on self-reported sexual functioning, combining data from two independent studies, one large and naturalistic and the other a smaller but controlled clinical trial. Naturalistic use of psychedelics was associated with improvements in several facets of sexual functioning and satisfaction, including improved pleasure and communication during sex, satisfaction with one’s partner and physical appearance. Convergent results were found in a controlled trial of psilocybin therapy versus an SSRI, escitalopram, for depression. In this trial, patients treated with psilocybin reported positive changes in sexual functioning after treatment, while patients treated with escitalopram did not. Despite focusing on different populations and settings, this is the first research study to quantitively investigate the effects of psychedelics on sexual functioning. Results imply a potential positive effect on post-acute sexual functioning and highlight the need for more research on this.

Eliciting Depression Patients' Preferences for Medication Management: A Protocol for Discrete Choice Experiment.

Depression threatens people's lives and imposes huge economic burden. Antidepressant therapy is the first-line treatment for depression, and patient adherence to medication is the key to successful treatment. Depression patients have poor medication adherence, which leads to failure of depression management and significantly poorer clinical outcomes. Incorporating patient preferences into clinical decisions can improve uptake rates, optimize treatment adherence. A discrete choice experiment (DCE) can elicit and quantify individual preferences. Previous DCE studies were conducted in developed countries and ignored the influences of factors other than the medication. This paper outlines an ongoing DCE that aims to (1) explore medication-management-related characteristics that may affect depression patients' adherence to antidepressant, (2) elicit how depression patients consider the trade-offs among different medication managements. The six attributes and their levels were developed through a literature review, semi-structured interviews and experts and focus group discussions. A fractional factorial design in the software Ngene 1.2 version was used to generate 36 choice sets, and they were divided into 3 blocks. A mixed logit model will be used to explore the patients' preferences, willingness to pay and uptake rate of depression patients for medication management attributes. The final questionnaire consists of three parts. The first is the introduction, which introduces the purpose of the study and the requirements of completing the questionnaire. This was followed by a general information questionnaire, which included sociodemographic characteristics. The last part is DCE tasks, which include 13 DCE choice sets, and each choice set include two alternative and one "opt-out" option. The pilot-test results showed the questionnaire was easy to understand and could be used in formal surveys. Our study shows how the development process of the study can be conducted and reported systematically and rigorously according to the theoretical foundation and design principles in DCE.

Socioeconomic status and access to mental health care: The case of psychiatric medications for children in Ontario Canada

We examine differences in the prescribing of psychiatric medications to lower-income and higher-income children in the Canadian province of Ontario using rich administrative data that includes diagnosis codes and physician identifiers. Our most striking finding is that conditional on diagnosis and medical history, low-income children are more likely to be prescribed antipsychotics and benzodiazepines than higher-income children who see the same doctors. These are drugs with potentially dangerous side effects that ideally should be prescribed to children only under narrowly proscribed circumstances. Lower-income children are also less likely to be prescribed SSRIs, the first-line treatment for depression and anxiety conditional on diagnosis. Hence, socioeconomic differences in the prescribing of psychotropic medications to children persist even in the context of universal public health insurance and universal drug coverage.

The Effects of Remifentanil, Dexmedetomidine, and Metoral as Adjuncts to Thiopental on Hemodynamic Status After Electroconvulsive Therapy in Patients with Major Depressive Disorder: A Randomized Controlled Clinical Trial.

Depression is a prevalent mental disorder affecting more than 300 million people of all ages globally. Despite being the first-line treatment for depression, antidepressant medications are only effective for 60% - 70% of patients. Electroconvulsive therapy (ECT) is an effective treatment for severe cases, although it can result in short-term side effects. This study aimed to compare the effectiveness of remifentanil, dexmedetomidine, and metoral as premedications for ECT in patients with major depressive disorder (MDD). In this prospective double-blinded randomized controlled clinical trial, a total of 120 MDD patients aged 18 - 60 were included. They were randomly assigned to receive remifentanil, dexmedetomidine, or metoral in combination with thiopental before ECT. Hemodynamic responses (mean arterial blood pressure, pulse rate, arterial blood oxygen saturation), seizure duration, recovery time, agitation scores, and patient satisfaction scores (reverse coded) were measured and compared. Dexmedetomidine exhibited superior hemodynamic control with lower mean arterial blood pressure (P < 0.001) and pulse rate (P < 0.001) than remifentanil and metoral. Patients receiving dexmedetomidine or remifentanil showed reduced agitation (P < 0.001) and better satisfaction than the metoral group (P < 0.001). Remifentanil displayed intermediate outcomes, while metoral exhibited the least favorable results. Seizure duration was not significantly different between the dexmedetomidine and remifentanil groups (P = 0.843). Dexmedetomidine is considered the most satisfactory group due to the better control of blood pressure, heart rate, and agitation and better patient satisfaction despite the longer recovery time.

Effect of citalopram on sex hormones and testicular histomorphology in male albino rats

Introduction: Citalopram, a selective serotonin reuptake inhibitor (SSRI), is commonly used as a first-line treatment for depression. However, the potential effects of Citalopram on testicular histo-morphology and hormone levels have not been extensively studied. This study aimed to evaluate the impact of Citalopram on the microscopic structure of the testes and the levels of serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in male albino rats. Aims: The primary objective of this study was to assess the effects of Citalopram on testicular histo-morphology using the Johnson scoring system. The secondary objective was to measure the levels of serum testosterone, LH, and FSH in rats treated with varying doses of Citalopram. Methodology: A total of 25 healthy male albino rats were divided into five groups: control, group I, group II, group III, and group IV. The rats in groups I to IV were orally administered 10 mg, 20 mg, 30 mg, and 40 mg of Citalopram, respectively, while the control group received oral distilled water. The dosages were adjusted based on the suggested doses for humans and scaled according to the rats' weight.

Contradictions, methodological flaws, and potential for misinterpretations in ranking treatments of depression.

In this journal Malhi et al. recommended cognitive-behavior therapy (CBT), antidepressants, and counseling ahead of short-term psychodynamic therapy (STPP) referring to UK NICE guidelines for depression. However, these recommendations continue the ambiguous and therefore confusing NICE guidelines, which on the one hand list the above treatments as equal options as first-line treatment for depression and emphasizes the importance of patient preference and implementations factors, but on the other hand rank these first-line treatments, implying superiority of some treatments over others. Furthermore, we highlight several methodological flaws of the NICE treatment ranking and that the NICE treatment ranking is not justified by NICE's own and independent evidence and criteria. Presently it is not clear which patients benefit from which empirically-supported treatment. Thus, we continue to discourage the devaluing of efficacious treatments so that as many patients as possible may benefit from them.

Deprexis® Acceptability study in REal life (DARE): study design

IntroductionDepression is a leading cause of disability, worldwide. Recently, WHO highlighted the negative impact of recent crises (COVID-19 pandemic, war in Ukraine, economic crisis).Although most international guidelines recommend psychotherapies as first-line treatment of depression, access remains scarce in France due to limited availability of trained clinicians (notably those with CBT certification), high cost for patient in a context of non-reimbursement and fear of stigmatization (Coldefy M. HCAA, 2022/04,19). Therefore, online blended psychological treatment such as deprexis® could increase access to care for people with depression. It presents several advantages such as easy access, scalability, and a proven efficacy (Twomey et al. PLoS One. 2020;15(1):e022810).ObjectivesThis study aims to test real-life acceptability of deprexis® for people with depression in France outside a reimbursement pathway.Primary objective of this cross-sectional study is to measure acceptability of deprexis® a new digital therapy in France.Questionnaire includes acceptability of deprexis® assessed with patient willingness to complete deprexis® course, reasons of refusal, when needed, demographics and depression characteristics. The secondary objectives are to study 1/ acceptability according to type of center (Hospital based, Community Based or private practice) and type of practitioners (psychiatrists or psychologists), 2/ differences in acceptability according to severity’s level (evaluated with PHQ 9), 3/ differences in acceptability according to administration or not of a treatment (including psychotherapy), 4/ differences in acceptability according to prescriber’s profile (age, sex, place and type of practice), 5/ identification of reasons for refusal , and 6/ analyze refusal rate over time.MethodsDARE is as a cross-sectional study in which deprexis® is suggested to any patient meeting the inclusion criteria over the fixed inclusion period June-December 2022Inclusion criteria are: 1/ depression, 2/ age between 18 and 65 years, 3/ speak French sufficiently, 4/ access to Internet with a device to connect to deprexis® platform.Exclusion criteria are diagnosis of bipolar disorder, psychotic symptoms and/or suicidal thoughts during the current episode.All investigators received a video-based training on deprexis® before inclusion to make sure they all have same level of information and understanding on the program.ResultsThe study is currently recruiting. Data will be available for EPA congress.ConclusionsIt is a first time a digital therapy is completing the current therapeutic options for the treatment of depression in France. Acceptability of this innovation by both patients and Healthcare providers is a first step.DARE may allow to have a better understanding of the acceptability of a digital therapy in the treatment of depression in France and identify the different factors influencing it in a natural setting.Disclosure of Interest O. Amiot Consultant of: Ethypharm Digital Therapy, A. H. Clair Consultant of: Ethypharm Digital Therapy, P. Courtet Consultant of: Ethypharm Digital Therapy, E. Fakra Consultant of: Ethypharm Digital Therapy, V. Narboni Employee of: Ethypharm Digital Therapy, F. Gheysen Consultant of: Ethypharm Digital Therapy, E. Haffen Consultant of: Ethypharm Digital Therapy, D. Drapier Consultant of: Ethypharm Digital Therapy, L. Lecardeur Consultant of: Ethypharm Digital Therapy

Когнитивно-поведенческая терапия депрессии: руководство

&lt;p&gt;Depression is one of the most common, disabling, and lethal (e.g., suicide) forms of psychopathology. Nearly 300 million people struggle with depression worldwide, and it is the leading cause of disability for people ages 15-44. Unfortunately, most people with depression do not receive the treatment they need. There is limited access to mental health services, and when services are available, the treatments used tend to have limited scientific support. This is because many mental health professionals are not trained in empirically supported treatments, are ambivalent about the role of science in clinical practice, and have limited access to scientific research (e.g., journal paywalls). The purpose of this special issue article is to provide a free and easy to use primer on Cognitive Behavioral Therapy (CBT) for depression. CBT is the most studied form of psychotherapy, has a strong theoretical basis, can be implemented by therapists of varying experience levels, and is as effective or more effective than existing treatments, including medication. CBT may not work for every client, but it is the best place to start. In this article, we discuss: a) why CBT should be the first-line treatment for depression, b) the theoretical basis of CBT for depression, and c) a basic overview of how to administer 12 sessions of CBT for depression. We also provide a reading list and supplemental open-access materials (e.g., a cognitive skills workbook) for further education.&lt;/p&gt;

Comparing skill enhanced and standard cognitive behavioral therapy for depression: a protocol for a randomized trial

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Cognitive behavioral therapy (CBT) features prominently among the first-line treatments for depression. The development of CBT skills is associated with both symptom reductions and reduced risk for relapse, suggesting that improvements in CBT skills might be important to the benefits of CBT. Nonetheless, standard CBT places modest emphasis on the development of these skills.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; In this paper, we describe a randomized clinical trial testing the benefits of a variation of CBT that places greater emphasis on teaching patients CBT skills and makes patients' independent use of these skills a central therapeutic goal. Patients in this study (75 per condition) are being randomized to 12 weeks of standard or skill enhanced CBT for depression. The primary outcomes are change in symptoms and change in CBT skills. We will also evaluate the process of change in the treatments.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study has the potential to suggest an approach to enhancing CBT outcomes through greater focus on patients developing and independently using CBT skills. It will also provide an important context for understanding the role that CBT skills play in the therapeutic outcomes of CBT.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Trial registration:&lt;/strong&gt; The trial has been registered in ClinicalTrials.gov. Registration number: NCT04673513; registered on 17 December 2020.&lt;/p&gt;

Identifying the Common Genetic Basis of Antidepressant Response

BackgroundAntidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic analysis of prospectively assessed antidepressant response in major depressive disorder to gain insight into the underlying biology and enable out-of-sample prediction. MethodsGenome-wide analysis of remission (nremit = 1852, nnonremit = 3299) and percentage improvement (n = 5218) was performed. Single nucleotide polymorphism–based heritability was estimated using genome-wide complex trait analysis. Genetic covariance with eight mental health phenotypes was estimated using polygenic scores/AVENGEME. Out-of-sample prediction of antidepressant response polygenic scores was assessed. Gene-level association analysis was performed using MAGMA and transcriptome-wide association study. Tissue, pathway, and drug binding enrichment were estimated using MAGMA. ResultsNeither genome-wide association study identified genome-wide significant associations. Single nucleotide polymorphism–based heritability was significantly different from zero for remission (h2 = 0.132, SE = 0.056) but not for percentage improvement (h2 = −0.018, SE = 0.032). Better antidepressant response was negatively associated with genetic risk for schizophrenia and positively associated with genetic propensity for educational attainment. Leave-one-out validation of antidepressant response polygenic scores demonstrated significant evidence of out-of-sample prediction, though results varied in external cohorts. Gene-based analyses identified ETV4 and DHX8 as significantly associated with antidepressant response. ConclusionsThis study demonstrates that antidepressant response is influenced by common genetic variation, has a genetic overlap schizophrenia and educational attainment, and provides a useful resource for future research. Larger sample sizes are required to attain the potential of genetics for understanding and predicting antidepressant response.

Effectiveness of a Guided Web-Based Intervention to Reduce Depressive Symptoms before Outpatient Psychotherapy: A Pragmatic Randomized Controlled Trial

Introduction: Psychotherapy is a first-line treatment for depression. However, capacities are limited, leading to long waiting times for outpatient psychotherapy in health care systems. Web-based interventions (WBI) could help to bridge this treatment gap. Objective: This study investigates the effectiveness of a guided cognitive-behavioral WBI in depressive patients seeking face-to-face psychotherapy. Methods: A 2-arm randomized controlled trial was conducted. Depressive patients (n = 136) recruited from the waiting lists of outpatient clinics were randomly assigned to an intervention group (IG; treatment as usual [TAU] + immediate access to WBI) or a control group (CG; TAU + access to WBI after follow-up). Depressive symptoms and secondary outcomes were assessed at baseline, 7 weeks, and 5 months after randomization. Results: Mixed-model analyses revealed a significant group × time interaction effect on depressive symptoms (F_{2, 121.5} = 3.91; p < 0.05). Between-group effect sizes were d = 0.55 at 7 weeks and d = 0.52 at 5 months. The IG was superior regarding psychological symptoms and mental health quality of life but not on physical health quality of life, attitudes, motivation for psychotherapy, or subjective need and uptake of psychotherapy. Conclusions: Patients waiting for face-to-face psychotherapy can benefit from a WBI when compared to TAU. Despite the reduction of depressive symptoms in the IG, the uptake of subsequent psychotherapy was still high in both groups. The effects remained stable at the 5-month follow-up. However, this study could not determine the proportion of specific intervention effects vs. nonspecific effects, such as positive outcome expectations or attention. Future research should focus on the long-term effects and cost-effectiveness of WBI before psychotherapy.

Recognition and management of depression in early psychosis.

Depression in first-episode psychosis (FEP) is highly prevalent and associated with poor outcomes; it has become increasingly recognised and adopted in national and international guidelines for psychosis. Using a 26-item questionnaire, this study aimed to explore if this shift has led to greater recognition among UK psychiatrists, and more effective management of depression in FEP. Of the 297 respondents, 54.4% observed depression occurring in chronic psychosis, with the least number of respondents (17.7%) identifying depression occurring frequently during FEP. Although there was reasonable agreement in the use of antidepressants as a first-line treatment for depression (70% prescribing antidepressants), there was uncertainty around assessing depression and delineating from psychosis symptoms, and particularly negative symptoms. Evidence-based treatments for comorbid depression in psychosis will lead to clearer national guidelines, allowing for optimal management of depression in early psychosis, potentially leading to improved outcomes for these individuals.

Pneumopathie chronique à éosinophiles induite par la sertraline

Sertraline is a selective serotonin reuptake inhibitor which is often used as first-line treatment for depression. Several patterns of interstitial lung disease attributable to sertraline have been reported in the literature. A 69-year-old patient, who had been taking sertraline to treat severe depression for 10months, presented with a deterioration in his general condition and respiratory symptoms found to be associated with bilateral pneumonitis. An exhaustive assessment did not reveal any infectious or autoimmune aetiology. Transthoracic lung biopsy revealed a pattern of eosinophilic lung disease. Sertraline-induced lung toxicity was then suspected and this treatment was therefore stopped. The patient's symptoms resolved and the chest imaging normalized. Our observation suggests that sertraline was the cause of chronic eosinophilic pneumonia characterized by an insidious clinical presentation several months after starting the medication. Given its widespread prescription, we encourage any clinician facing this disease to pay attention to possible drug-induced origins of lung disease.

Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Induced by Long-Term Use of Citalopram and Short-Term Use of Naproxen

Patient: Female, 88-year-oldFinal Diagnosis: Syndrome of inappropriate antidiuretic hormone secretionSymptoms: Decreased appetite • malaise • nauseaMedication:—Clinical Procedure: LaboratorySpecialty: Endocrinology and Metabolic • Geriatrics • NephrologyObjective:Rare co-existance of disease or pathologyBackground:Use of selective serotonin reuptake inhibitors (SSRIs) has been reported to be associated with the syndrome of inappropriate antidiuretic hormone (SIADH), although it is uncommon. Nonsteroidal anti-inflammatory drugs (NSAIDs), as a sole agent, are an even rarer cause of SIADH. Despite being documented in the literature, the understanding of the mechanism of both agents is limited. Here, we report a case of a patient taking both of these medications, a dangerous combination that led to the development of SIADH.Case Report:An 88-year-old woman with a history of asymptomatic chronic hyponatremia presented to our facility with symptomatic acute-on-chronic hyponatremia after she started using naproxen in addition to her daily citalopram. Her hyponatremia symptoms resolved after discontinuing these 2 offending agents, along with administration of fluid restriction and oral sodium supplements.Conclusions:Naproxen is commonly prescribed and is often taken by elderly patients to control long-term or short-term pain. SSRIs, on the other hand, are a first-line treatment for depression and are usually prescribe by a psychiatrist. Hyponatremia is a rare medication adverse effect that should be kept in mind when treating these patients with either of these medications, and should especially be considered when combining them. Medication reconciliation should be done carefully by the provider to avoid adverse effects and drug interactions. When hyponatremia is encountered, options for future medication prescriptions include rechallenging with the same medication, switching to a different medication with the same mechanism of action, or using a medication from another class altogether. Monitoring of serum sodium level is warranted when titrating the offending agent.

The preclinical discovery and development of agomelatine for the treatment of depression

ABSTRACT Introduction Under the treatment of commonly used antidepressants, many patients with major depressive disorder (MDD) do not achieve remission. All previous first-line treatments for depression have focused on the enhancement of monoaminergic activity. Agomelatine was the first antidepressant with a mechanism of action extending beyond monoaminergic neurotransmission. Areas covered The aim of this case history is to describe the discovery strategy and development of agomelatine. The pharmacodynamic profile of the drug is briefly presented. The article summarizes (a) the preclinical behavioral data on agomelatine’s effects on depressive-like behavior, anxiety, and circadian rhythmicity disruptions, and (b) the results of early preclinical studies on safety, efficacy in MDD, and the risk-benefit pharmacological profile. Furthermore, the article examines findings of post-marketing research on safety, efficacy, and cost-effectiveness of the drug. Expert opinion There is now evidence supporting the clinical efficacy and safety profile of agomelatine in the acute-phase treatment of MDD. Agomelatine may be more effective in specific subgroups of MDD patients, those with severe anxiety symptoms or disturbed circadian profiles. Its antidepressant and anxiolytic activities are due to synergy between its melatonergic and 5-hydroxytryptaminergic effects. Since its discovery, novel compounds acting on the melatonergic system have been under investigation for the treatment of MDD.

Effectiveness and cost-effectiveness of group support psychotherapy delivered by trained lay health workers for depression treatment among people with HIV in Uganda: a cluster-randomised trial

WHO recommends the use of psychological interventions as first-line treatment for depression in low-income and middle-income countries. However, evaluations of the effectiveness and cost-effectiveness of such interventions among people with HIV are scarce. Our aim was to establish the effectiveness of group support psychotherapy (GSP) delivered by lay health workers for depression treatment among people living with HIV in a rural area of Uganda on a large scale. In this cluster-randomised trial, we included 30 health centres offering HIV care. These were randomly assigned to deliver either GSP or group HIV education (GHE). Randomisation, in a ratio of 1:1, was achieved by health centre managers separately picking a paper containing the intervention allocation from a basket. Participants were people living with HIV, aged 19 years and older, with mild to moderate major depression assessed with the Mini International Neuropsychiatric Interview depression module, taking antiretroviral therapy, and antidepressant-naive. Group sessions were led by trained lay health workers once a week for 8 weeks. The primary outcomes were the proportion of participants with major depression and function scores at 6 months post-treatment, analysed by intention to treat by means of multilevel random effect regression analyses adjusting for clustering in health centres. This trial is registered with the Pan African Clinical Trials Registry, PACTR201608001738234. Between Sept 13 and Dec 15, 2016, we assessed 1473 individuals, of whom 1140 were recruited from health centres offering GSP (n=578 [51%]) or GHE (n=562 [49%]). Two (<1%) participants in the GSP group were diagnosed with major depression 6 months post-treatment compared with 160 (28%) in the GHE group (adjusted odds ratio=0·01, 95% CI 0·003-0·012, p<0·0001). The mean function scores 6 months post-treatment were 9·85 (SD 0·76) in the GSP group and 6·83 (2·85) in the GHE group (β=4·12; 95% CI 3·75-4·49, p<0·0001). 36 individuals had 63 serious adverse events, which included 25 suicide attempts and 22 hospital admissions for medical complications. The outcomes of these serious adverse events included 16 deaths, 4 of which were completed suicides (GSP=2; GHE=2), and 12 of which were HIV-related medical complications (GSP=8; GHE=4). Cost-effectiveness estimates showed an incremental cost-effectiveness ratio of US$13·0 per disability-adjusted life-year averted, which can be considered very cost-effective in Uganda. Integration of cost-effective psychological treatments such as group support psychotherapy into existing HIV interventions might improve the mental health of people living with HIV. MQ Transforming Mental Health and Grand Challenges Canada.

Risks of hospitalization for upper gastrointestinal bleeding in users of selective serotonin reuptake inhibitors after Helicobacter pylori eradication therapy: a propensity score matching analysis.

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for depression but there is a concern about the risk of upper gastrointestinal bleeding (UGIB). Past studies, however, are largely confounded by the presence of Helicobacter pylori (HP). To evaluate the UGIB risk of SSRI users after treatment for HP. This was a propensity score (PS) matched cohort study with patients who used SSRI after receiving HP eradication therapy from the Hong Kong territory-wide healthcare database. The primary outcome was hospitalisation for nonvariceal UGIB. PS matching analysis with a ratio of 1:2 plus Cox regression model was used to compute the hazards ratios (HR) and 95% CI of UGIB risk. In this study, 3358 SSRI users and 57906 non-users were included. The median follow-up duration was 7.74 (interquartile range 5.32-10.42) years. The crude incidence of hospitalisation for UGIB was 3.98 (95% CI 3.80-4.16) per 1000 person-years. In the PS matching analysis of 3358 SSRI users with 6716 non-users, SSRI was associated with a higher risk of UGIB compared to non-users (HR 1.95, 95% CI 1.41-2.70). This result was consistent in sensitivity analysis with 1:1 PS matching (HR 2.13, 95% CI 1.50-3.02) and multivariable analysis with 1-month intervals (HR 1.81, 95% CI 1.34-2.45) or 3-month intervals (HR 1.61, 95% CI 1.20-2.17). After stratifying by age, the increased risk of SSRI was only significant among patients >50years. SSRI users have a higher risk of hospitalisation for nonvariceal UGIB after treatment for HP, particularly among older patients.