Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action.
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ABSTRACT:
SUBMITTER: Millan MJ
PROVIDER: S-EPMC9251978 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Objective:Despite multiple drugs available, a large proportion of patients with generalized anxiety disorder (GAD) do not show adequate response and remission. Thus, additional novel pharmacological agents are needed to increase treatment option for GAD. We aimed to investigate efficacy and safety of agomelatine in the treatment of GAD by conducting a meta-analysis. Methods:An extensive search of multiple databases and clinical trial registries were conducted. Mean change in total scores on Hamilton Anxiety Rating Scale (HAM-A) from baseline to endpoint was our primary outcome measure. Secondary efficacy measures included response and remission rates, as defined by a 50% or greater reduction in HAM-A total scores and a score of 7 or less in HAM-A total scores at study endpoint respectively. Results:Four published double blinded, randomized, placebo-controlled trials were included in this meta-analysis. Agomelatine more significantly (standardized mean difference = -0.56, p = 0.004) improved HAM-A total scores than placebo. The odds ratios (ORs) of agomelatine over placebo for response and remission rates were 3.75 (p < 0.00001) and 2.74 (p < 0.00001), respectively. Agomelatine was generally well tolerated with insignificance in dropout rate, somnolence, headache, nasopharyngitis, and dizziness compared with placebo. However, agomelatine showed significantly higher incidence of liver function increment (OR = 3.13, p = 0.01) and nausea (OR = 3.27, p = 0.02). Conclusion:We showed that agomelatine may be another treatment option in patients with GAD. However, the results should be interpreted and translated into clinical practice with caution because the meta-analysis was based on limited numbers of clinical trials.
| S-EPMC7383014 | biostudies-literature
Project description:Mechanisms underlying anxiety disorders remain elusive despite the discovery of several associated genes. We constructed the protein-protein interaction networks (interactomes) of six anxiety disorders and noted enrichment for striatal expression among common genes in the interactomes. Five of these interactomes shared distinctive overlaps with the interactomes of genes that were differentially expressed in two striatal compartments (striosomes and matrix). Generalized anxiety disorder and social anxiety disorder interactomes showed exclusive and statistically significant overlaps with the striosome and matrix interactomes, respectively. Systematic gene expression analysis with the anxiety disorder interactomes constrained to contain only those genes that were shared with striatal compartment interactomes revealed a bifurcation among the disorders, which was influenced by the anterior cingulate cortex, nucleus accumbens, amygdala and hippocampus, and the dopaminergic signaling pathway. Our results indicate that the functionally distinct striatal pathways constituted by the striosome and the matrix may influence the etiological differentiation of various anxiety disorders.
| S-EPMC8443595 | biostudies-literature
Project description:Prospective epidemiological studies found that generalized anxiety disorder (GAD) can impair immune function and increase risk for cardiovascular disease or events. Mechanisms underlying the physiological reververations of anxiety, however, are still elusive. Hence, we aimed to investigate molecular processes mediating effects of anxiety on physical health using blood gene expression profiles of 546 community participants. Of these, 179 met the status of controls and 157 cases of anxiety.
2014-12-01 | GSE61672 | GEO
Project description:Approximately 16 million people in the United States suffer from anxiety disorders alone, while another 12 million experience both anxiety and at least one other psychiatric condition. Generalized anxiety disorder (GAD) has lifetime prevalence rates between 5% and 6%. Treatment of GAD is aimed primarily at symptom reduction. Duloxetine, a serotonin norepinephrine reuptake inhibitor (SNRI), received Food and Drug Administration (FDA) approval for the treatment of GAD in 2007. This article reviews the pharmacologic profile and seminal clinical trials associated with the FDA indication of duloxetine for GAD. A literature search performed using PubMed with the keywords "duloxetine", "gad", "generalized anxiety disorder", and "venlafaxine XR" yielded 27 articles. We also focused on papers that pooled data from these seminal studies. Data on file from Eli Lilly were also reviewed, including data from the Eli Lilly website. Based on this search, duloxetine was found to be an FDA-approved treatment option for GAD that has been studied in several double-blind, placebo-controlled clinical trials. This review of duloxetine will help physicians to interpret clinical studies properly and also help them to make an informed decision about which patients are the most appropriate candidates for a trial of duloxetine.
| S-EPMC2695226 | biostudies-literature
Project description:Background: Generalized anxiety disorder (GAD) is common in young adults, yet few studies have established the psychometric properties of the GAD-7 screener in college students. Methods: A secondary analysis of three studies was conducted to determine GAD-7 factor structure stability, create a GAD-Mini version using standard procedures, and evaluate the psychometric properties, validity, sensitivity, specificity, and predictive values of both versions in young adults. Results: Exploratory and confirmatory principal components analysis indicated the GAD-7 has a single factor structure with strong loadings, reliability, and stability across data collected in three studies. Data from all studies met criteria indicative of good to excellent model fit. Iterative confirmatory principal components analyses revealed the most parsimonious group of items that maintained scale unidimensionality, strong loadings, and high reliability was two items (not able to stop or control worrying and worried too much). Both the GAD-7 and GAD-Mini exhibited good construct and convergent validity. Specificity, sensitivity, and negative predictive value were high, and positive predictive value was moderate to high for the GAD-Mini. Conclusions: The GAD-Mini is a psychometrically sound tool that can serve as a step toward universal screening in clinical practice and contribute to early treatment and improved health outcomes for GAD.
| S-EPMC7541941 | biostudies-literature
Project description:Cannabis has a long history of medical use. Although there are many cannabinoids present in cannabis, Δ9tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are the two components found in the highest concentrations. CBD itself does not produce typical behavioral cannabimimetic effects and was thought not to be responsible for psychotropic effects of cannabis. Numerous anecdotal findings testify to the therapeutic effects of CBD, which in some cases were further supported by research findings. However, data regarding CBD's mechanism of action and therapeutic potential are abundant and omnifarious. Therefore, we review the basic research regarding molecular mechanism of CBD's action with particular focus on its analgesic potential. Moreover, this article describes the detailed analgesic and anti-inflammatory effects of CBD in various models, including neuropathic pain, inflammatory pain, osteoarthritis and others. The dose and route of the administration-dependent effect of CBD, on the reduction in pain, hyperalgesia or allodynia, as well as the production of pro and anti-inflammatory cytokines, were described depending on the disease model. The clinical applications of CBD-containing drugs are also mentioned. The data presented herein unravel what is known about CBD's pharmacodynamics and analgesic effects to provide the reader with current state-of-art knowledge regarding CBD's action and future perspectives for research.
| S-EPMC7700528 | biostudies-literature
Project description:BackgroundPeople differ in their affective styles, which refers to habitual use of emotion regulation (ER) strategies. Previous research has shown that mental health is associated with an individual's adaptive flexibility of emotion regulation strategies rather than any one particular ER strategy.MethodsThe present study employed a person-centered approach using latent profile analyses to distinguish patients with generalized anxiety disorder based on their responses on an affective styles measure.ResultsResults of the latent profile analysis supported a three-class solution. Class 1 (26% of participants) identified individuals with the lowest scores of each affective style; class 2 (10%) included individuals with the highest scores of each style; and class 3 (64%) consisted of individuals who scored in the mid-range of each affective style. Greater ER flexibility was associated with better emotional functioning and quality of life.ConclusionsPatients with GAD differ in ER flexibility. The vast majority of patients appear to have only moderate or low ER flexibility. Those individuals with high ER flexibility show a greater quality of life and less emotional distress.
| S-EPMC7357573 | biostudies-literature
Project description:Despite the success of cognitive behavioral therapies (CBT) for emotional disorders, a sizable subgroup of patients with complex clinical presentations, such as patients with generalized anxiety disorder, fails to evidence adequate treatment response. Emotion Regulation Therapy (ERT) integrates facets of traditional and contemporary CBTs, mindfulness, and emotion-focused interventions within a framework that reflects basic and translational findings in affect science. Specifically, ERT is a mechanism-targeted intervention focusing on patterns of motivational dysfunction while cultivating emotion regulation skills. Open and randomized controlled psychotherapy trials have demonstrated considerable preliminary evidence for the utility of this approach as well as for the underlying proposed mechanisms. This article provides an illustration of ERT through the case of "William." In particular, this article includes a case-conceptualization of William from an ERT perspective while describing the flow and progression of the ERT treatment approach.
| S-EPMC4973631 | biostudies-literature
Project description:BackgroundGeneralized social phobia (GSP) and generalized anxiety disorder (GAD) are both associated with emotion dysregulation. Research implicates dorsal anterior cingulate cortex in both explicit emotion regulation (EER) and top-down attentional control (TAC). Although studies have examined these processes in GSP or GAD, no work compares findings across the two disorders or examines functioning in cases comorbid for both disorders (GSP/GAD). Here we compare the neural correlates of EER and TAC in GSP, GAD, and GSP/GAD.MethodsMedication-free adults with GSP (EER n = 19; TAC n = 18), GAD (EER n = 17; TAC n = 17), GSP/GAD (EER n = 17; TAC n = 15), and no psychopathology (EER n = 18; TAC n = 18) participated. During EER, individuals alternatively viewed and upregulated and downregulated responses to emotional pictures. During TAC, they performed an emotional Stroop task.ResultsFor both tasks, significant group × condition interactions emerged in dorsal anterior cingulate cortex and parietal cortices. Healthy adults showed significantly increased recruitment during emotion regulation, relative to emotion-picture viewing. GAD, GSP, and GSP/GAD subjects showed no such increases, with all groups differing from healthy adults but not from each other. Evidence of emotion-related disorder-specificity emerged in medial prefrontal cortex and amygdala. This disorder-specific responding varied as a function of emotion content but not emotion-regulatory demands.ConclusionsGSP and GAD both involve reduced capacity for engaging emotion-regulation brain networks, whether explicitly or via TAC. A reduced ability to recruit regions implicated in top-down attention might represent a general risk factor for anxiety disorders.
| S-EPMC3424322 | biostudies-literature
Project description:We conducted the first genome-wide association study (GWAS) in Generalized Anxiety Disorder (GAD) to identify potential predictors of venlafaxine XR treatment outcome. Ninety-eight European American patients participated in a venlafaxine XR clinical trial for GAD, with Hamilton Anxiety Scale (HAM-A) response/remission at 24 weeks as the primary outcome measure. All participants were genotyped with the Illumina PsychChip, and 266,820 common single nucleotide polymorphisms (SNPs) were analyzed. Although no SNPs reached genome-wide significance, 8 SNPs were marginally associated with treatment response/remission and HAM-A reduction at week 12 and 24 (p<0.00001). Several identified genes may indicate markers crossing neuropsychiatric diagnostic categories.
| S-EPMC5798606 | biostudies-literature