Hamilton Anxiety Rating Scale Total Score Research Articles

Baseline symptom severity and efficacy of Silexan in patients with anxiety disorders: A symptom-based, patient-level analysis of randomized, placebo-controlled trials.

The influence of baseline severity on the efficacy of Silexan, a proprietary essential oil from Lavandula angustifolia, in anxiety disorders has not been investigated in a pooled dataset. We report on an individual patient data analysis of all five double-blind, randomized, placebo-controlled trials with Silexan in anxiety disorders. Eligible participants received Silexan 80mg/d or placebo for 10 weeks. Analyses were based on the Hamilton Anxiety Rating Scale (HAMA), its psychic and somatic anxiety subscores, and the Clinical Global Impressions (CGI) scale. To correlate baseline severity with outcome, patients were segregated into mild, moderate, and severe cases. Altogether 1,172 patients (Silexan, n=587; placebo, n=585) were analyzed. For the HAMA total score, we found a significant association between the score at baseline and the treatment effect of Silexan versus placebo at week 10 (p<0.001). HAMA items from the somatic domain scored lower at baseline and showed less improvement than items from the psychic domain, particularly in patients with mild or moderate baseline symptoms. For CGI item 2 (global improvement), significant efficacy favoring Silexan were observed in mild, moderate, and severe baseline symptom severity. Although significant improvements were found for all subsets, the more severe the initial symptoms, the greater the treatment effects documented by the HAMA. Overall this analysis confirms that Silexan is an effective treatment option in early or mild stages of anxiety disorder. Given its favorable safety profile, Silexan can thus fill a therapeutic gap in the treatment of (subsyndromal) anxiety disorders.

Sleep Disturbances in Panic Disorder with Comorbid Complex PTSD: A Possible Relationship and Different Psychopathology?

Several studies have shown the possible link between trauma and sleep disturbances, particularly in anxiety disorders. This issue could be because sympathetic hyperarousal is central to both disorders, probably caused by a dysregulation of the noradrenergic system. This study aimed to establish if the comorbidity with complex post-traumatic stress disorder (cPTSD) is associated with sleep disturbances in panic disorder (PD) and if the presence of poor sleep quality is associated with a higher psychopathological burden. Participants (N = 211) with PD completed the International Trauma Questionnaire concerning their most troubling experience, the Hamilton Anxiety Rating Scale (HAM-A), and the Pittsburgh Sleep Quality Index (PSQI) to assess anxiety symptoms and sleep disturbances, respectively. The sample was divided into two subgroups based on the presence of cPTSD. No significant differences emerged in the bivariate analyses for what concerns sociodemographic features. As for the scores of the psychopathological scales, the analysis highlighted statistically significant differences between the subgroups. Subjects with cPTSD reported significantly higher HAM-A total scores. As for the disturbances in self-organization (DSO) and PSQI scores, these were all significantly higher in the cPTSD subsample. At the logistic regression, the presence of cPTSD was inserted as the dependent variable, while the PSQI scores of the subscales evaluating subjective sleep quality, sleep duration, sleep efficacy, and the use of hypnotics were used as independent variables. The presence of cPTSD was significantly associated with the PSQI subscores for subjective sleep quality and use of hypnotics. Patients with PD exhibit more severe sleep disturbances and a higher anxiety burden when experiencing prolonged trauma. Therapeutic advances are needed in this field to target these symptomatologic domains.

The effect psychobiotics on anxiety symptoms

IntroductionPsychobiotics are a group of probiotics that affect the central nervous system related functions and behaviors mediated by the gut-brain-axis via immune, humoral, neural, and metabolic pathways to improve not only the gastrointestinal function but also the antidepressant and anxiolytic capacity.ObjectivesAn assessment of psychobiotic and anti-anxiety effects a probiotic supplement containing Lactobacillus Plantarum CECT7485 and Lactobacillus Brevis CECT7480 (PLANTARUM) in patients with anxiety undergoing treatment with selective serotonin reuptake inhibitors (SSRI) antidepressants.MethodsSixty patients with mixed anxiety and depressive disorder (according to ICD-10 diagnostic criteria F41.2) were included in an 8-week open label study. Thirty participants received either SSRI antidepressants with PLANTARUM at a dose of 1.0 × 109 CFU once per day and thirty patients received SSRI antidepressants only. The severity of anxiety symptoms was assessed using Hamilton Anxiety Rating Scale (HAM-A) and General Anxiety Disorder Scale (GAD-7).ResultsAfter 8 weeks intervention, a significant reduction of HAM-A total score (from 37,8±5,3 to 23,6±4,4) was detected in patients with anxiety who prescribed SSRI antidepressants and PLANTARUM (p˂0,05), compared with participants who didn’t receive probiotics (p&gt;0,05). Also, a significant reduction of GAD-7 total score (from 21,7±3,3 to 12,5±2,4) was detected in patients with anxiety symptoms who received SSRI antidepressants and PLANTARUM (p˂0,01), compared with patients who didn’t intake probiotics (p&gt;0,05).ConclusionsThe present data illustrated that probiotic supplement PLANTARUM is a feasible for adjunctive to SSRI antidepressants intervention for anxiety treatment.Disclosure of InterestNone Declared

Efficacy of Silexan in patients with anxiety disorders: a meta-analysis of randomized, placebo-controlled trials

IntroductionWe report on a meta-analysis of Silexan, a proprietary active substance produced from Lavandula angustifolia, in subthreshold anxiety, mixed anxiety and depressive disorder (MADD), and generalized anxiety disorder (GAD).MethodsThe present analyses are based on all currently completed 5 double-blind, randomized, placebo-controlled trials investigating Silexan in adult out-patients who received Silexan 1 × 80 mg/day or placebo for ten weeks according to random assignment (n = 1213). Efficacy was assessed based on the Hamilton Anxiety Rating Scale (HAMA), several anxiety self-rating scales, the Clinical Global Impression (CGI) scale, and the Short Form-36 (SF-36) health status questionnaire.ResultsAfter ten weeks’ treatment, Silexan was significantly superior to placebo in reducing the HAMA total score (including the psychic and somatic anxiety sub-scores) and self-rated anxiety. Based on a ≥ 50% HAMA total score reduction, the responder rate ratio was 1.34 favoring Silexan, and the rate ratio of subjects much or very much improved according to the CGI was 1.51. Silexan was also significantly superior in improving the physical and mental health summary scores of the SF-36. There were no significant between-group differences concerning the occurrence of adverse events (AEs), serious AEs, and premature withdrawal due to AEs.ConclusionsThis meta-analysis demonstrates that Silexan exerts significant anxiolytic effects in subthreshold anxiety, GAD and MADD that were consistently reflected in investigator ratings and patient-reported outcomes, including improvement of health-related life-quality, while showing favorable tolerability and safety.

Tumor markers and depression scores are predictive of non-suicidal self-injury behaviors among adolescents with depressive disorder: A retrospective study

BackgroundNon-suicidal self-injury (NSSI) is an important risk factor for suicide in adolescents with depressive disorders; therefore, it is important to predict NSSI occurrence as early as possible. Disturbances in biological rhythms are characteristic manifestations of depressive disorders and can lead to immune dysfunction, leading to changes in tumor markers. This study aimed to produce an index that utilizes tumor markers to predict NSSI behaviors among adolescents with depressive disorders.MethodsA total of 120 hospitalized adolescent patients with depressive disorders aged 14–24 years were included in this study. Participants were divided into NSSI and non-NSSI groups based on self-reports using the Ottawa Self-Injury Inventory. Demographics, tumor marker concentrations, other peripheral blood indices, Hamilton Depression Rating Scale (HDRS) scores, and Hamilton Anxiety Rating Scale (HAMA) scores were compared between the two groups. Logistic regression analysis was conducted to develop a joint index, and a receiver operating characteristic (ROC) curve was created to predict NSSI behaviors among adolescents with depressive disorders.ResultsCompared with the non-NSSI group, the NSSI group had significantly higher insight, retardation, insomnia, hopelessness, psychiatric anxiety, total HDRS and HAMA scores, and significantly higher levels of cancer antigen 125 (CA-125), cancer antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA). In addition, a joint index was developed by combining CA-125, CA19-9, CEA, HDRS total score, HAMA total score and age using multiple logistic regression to predict NSSI behaviors. The area under the curve was 0.831, with a sensitivity and specificity of 0.734 and 0.891, respectively.ConclusionA combination of depression score, tumor marker levels, and age can identify NSSI behaviors among adolescents with depressive disorders.

Association Between Anxious Symptom Severity and Olfactory Impairment in Young Adults with Generalized Anxiety Disorder: A Case-Control Study.

ObjectiveThe findings of olfaction are inconsistent in anxiety disorders, and few studies have reported on the olfactory performance in generalized anxiety disorder (GAD). Therefore, we aim to investigate the olfactory function of patients with GAD and the association between olfactory function and anxiety symptoms.MethodsWe conducted a case–control study by selecting 107 patients with GAD and 107 healthy controls matched for sex and age, to investigate olfaction deficits in GAD and the association between anxiety severity and olfaction. All patients were treatment-naïve prior to the inclusion. Anxiety severity and olfaction were assessed by the Hamilton anxiety rating scale (HAM-A) and the Sniffin’ Sticks test (SST), respectively. Partial correlations were used to analyze the relationship between olfaction and anxiety severity. False discovery rate (FDR) correction was used in multi-correlation analyses.ResultsCompared with healthy controls, patients in the GAD group demonstrated odor threshold, discrimination and identification deficits. In the moderate/severe anxiety subgroup, discrimination score was significantly and inversely correlated with the somatic anxiety score (γ=−0.44, q = 0.03), and identification score was significantly and inversely correlated with the HAM-A total score (γ=−0.42, q= 0.04). The TDI score (the sum of threshold, discrimination and identification scores) was significantly and inversely correlated with the somatic (γ=−0.44, q = 0.04) and psychic (γ=−0.45, q = 0.04) anxiety scores in the moderate/severe anxiety subgroup.ConclusionThis study demonstrated the olfactory impairment in patients with GAD and that poorer odor discrimination was correlated with greater severity of somatic anxiety.

The effect on the anxiety level of the social support given to multiple sclerosis patients.

This is a descriptive study aiming at determining the effect on the anxiety level of the social support given to multiple sclerosis (MS) patients. This study was conducted with 123 MS patients. The data were collected the Multidimensional Scale of Perceived Social Support (MSPSS), the Hamilton Anxiety Rating Scale (HAM-A). The Multidimensional Scale of Perceived Social Support total score average was 57.18 ± 18.5, and the HAM-A total score average was 20.33 ± 10.42. A negative weak significant relationship was found between the MSPSS total score average and the HAM-A total score and its sub-dimensions. MS nurses should plan their anxiety management accordingly by giving holistic care and evaluating social support mechanisms.

Agomelatine for the Treatment of Generalized Anxiety Disorder: A Meta-Analysis.

ObjectiveDespite 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.MethodsAn 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.ResultsFour 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).ConclusionWe 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.

Psychotic symptoms in first-episode and drug naïve patients with major depressive disorder: Prevalence and related clinical factors.

Many patients with major depressive disorder (MDD) have been found to have psychotic symptoms. However, few studies have reported the prevalence of comorbid psychotic symptoms in first-episode drug naïve (FEDN) MDD patients. This study was to investigate the prevalence of psychotic symptoms and related risk factors in a large sample size of FEDN MDD patients in a Chinese population. A total of 573 patients with diagnosis of MDD at their first episode were recruited with their demographic and clinical data. Positive scale of the Positive and Negative Syndrome Scale was utilized for psychotic symptoms, Hamilton Anxiety Rating Scale (HAMA) for anxiety symptoms, and Hamilton Depression Rating Scale (HAMD) for depressive symptoms. The prevalence of psychotic symptoms in these MDD patients was 9.8%. MDD patients with psychotic symptoms had significantly higher HAMD and HAMA total scores than those without psychotic symptoms (both p < .001). A strong association was found between psychotic MDD and anxiety or suicide, with odds ratio of 33.097 for severe anxiety, and 5.012 for suicide. Our results suggest that psychotic symptoms are common in MDD patients at their first episode. The strong association between psychotic MDD and anxiety or suicide attempts demonstrates the importance of reducing anxiety symptoms in the treatment of psychotic MDD patients as well as the necessity to regularly assess suicide risk in MDD patients with psychotic symptoms to better prevent suicidal behavior.

Psychobiotics Regulate the Anxiety Symptoms in Carriers of Allele A of IL-1β Gene: A Randomized, Placebo-Controlled Clinical Trial.

Background Probiotic oral intake, via modulation of the microbiota-gut-brain axis, can impact brain activity, mood, and behavior; therefore, it may be beneficial against psychological distress and anxiety disorders. Inflammatory cytokines can influence the onset and progression of several neurodegenerative mood disorders, and the IL-1β rs16944 SNP is related to high cytokine levels and potentially affects mood disorders. The aim of this study was to examine the combined effect of IL-1β polymorphism and probiotic administration in mood disorder phenotypes in the Italian population. Methods 150 subjects were randomized into two different groups, probiotic oral suspension group (POSG) and placebo control group (PCG), and received the relative treatment for 12 weeks. Psychological profile assessment by Hamilton Anxiety Rating Scale (HAM-A), Body Uneasiness Test (BUT), and Symptom Checklist 90-Revised (SCL90R) was administered to all volunteers. Genotyping was performed on DNA extracted from salivary samples. Results After 12 weeks of intervention, a significant reduction of HAM-A total score was detected in the POSG (p < 0.01), compared to the PCG. Furthermore, IL-1β carriers have moderate risk to develop anxiety (OR = 5.90), and in POSG IL-1β carriers, we observed a reduction of HAM-A score (p = 0.02). Conclusions Consumption of probiotics mitigates anxiety symptoms, especially in healthy adults with the minor A allele of rs16944 as a risk factor. Our results encourage the use of probiotics in anxiety disorders and suggest genetic association studies for psychobiotic-personalized therapy.

Prevalence and clinical correlates of psychotic depression in first-episode and drug-naïve outpatients with major depressive disorder in a Chinese Han population

BackgroundFew systemic studies of psychotic depression (PD) have been conducted in first-episode and drug-naïve (FEDN) patients. This study was to examine the prevalence of PD and its clinical correlates in a large sample of FEDN outpatients with major depressive disorder (MDD) in a Chinese Han population, which to our best knowledge has not been studied. MethodsIn this cross-sectional study, a total of 1718 FEDN MDD outpatients were recruited. All patients were rated on the positive symptom subscale of the Positive and Negative Syndrome Scale (PANSS) for psychotic symptoms, the 17-item Hamilton Depression Rating Scale (HAMD-17) for depression and Hamilton Anxiety Rating Scale (HAMA) for anxiety. ResultsThe prevalence of PD was 10.0% (171/1718) in MDD patients. Compared to the non-PD patients, PD patients had significantly older age, lower educational levels, higher anxiety symptom score and were more likely to attempt suicide. Further logistic regression analysis indicated that PD was associated with older age, suicide attempt and comorbid anxiety (all p < 0.05). Multiple regression analyses showed that both HAMD and HAMA total scores were significantly associated with PANSS positive symptom subscale score. LimitationsOur cross-sectional study design does not show a direct causal relationship between psychiatric symptoms and related factors in patients with MDD. ConclusionsOur results suggest a high prevalence of PD in MDD patients in the acute early stage in a Chinese Han population, which is associated with demographic variables and clinical symptoms.

Influence of comorbid anxiety symptoms on cognitive deficits in patients with major depressive disorder

BackgroundMajor depressive disorder (MDD) patients with comorbid anxiety symptoms showed obvious cognitive deficits. However, it remains unclear whether comorbid anxiety symptoms will make a specific contribution to cognitive deficits in MDD. MethodsExecutive function, processing speed, attention and memory were assessed in 162 MDD patients, and 142 healthy controls (HCs) by a comprehensive neuropsychological battery. 14-item Hamilton Anxiety Rating Scale (HAM-A) was used for anxiety symptoms and MDD patients with HAM-A total score >14 were classified into MDD with comorbid anxiety (MDDA) group. A multivariate analysis of covariance and regression models was conducted to evaluate the effects of anxiety symptoms on cognitive deficits. ResultsThere were no significantly differences in all 4 cognitive domains between MDD alone and MDDA patients (all p < 0.05). In MDDA subgroup, HAM-A total score contributed to executive function and memory (both p < 0.05), while HAM-A psychic symptoms contributed to all 4 domains (all p < 0.05). Moreover, after controlling for the severity of depression, either anxiety symptoms shown as HAMA total score or psychic anxiety symptoms only contributed significantly to the executive function performance. LimitationsThe cross-sectional design made it hard to acquire a cognitive performance trajectory accompanied by the fluctuations in anxiety symptoms. ConclusionOur findings suggest that there is no significant difference in cognitive performance between MDD alone and MDDA patients. However, comorbid anxiety, especially psychic anxiety may contribute to extensive cognitive deficits in MDDA patients. Notably, anxiety symptoms only independently triggered executive dysfunction when eliminating effect of the severity of depression.

Efficacy and Safety of a Formulated Herbal Granula, Jiu Wei Zhen Xin, for Generalized Anxiety Disorder: A Meta-Analysis.

Background The traditional Chinese medicine formula Jiu Wei Zhen Xin Granula (JWZXG) is prescribed to treat generalized anxiety disorder (GAD) in China. This study was to assess the efficacy and safety of JWZXG in patients with GAD. Method Data were pooled from 14 randomized controlled trials involving the assessment of mean changes of Hamilton Anxiety Rating Scale (HAMA) total scores, response rates, adverse event rates, quality, publication bias, and risk of bias. Results Pooled analysis showed no significant difference in response rate (risk ratio 1.01, 95% CI [0.93–1.08]; Z test = 0.17, P = 0.86) and no significant difference between JWZXG group and azapirones group (RR 0.69, 95% CI [0.45, 1.06]; Z test = 1.69, P = 0.09) in rate of adverse events. Though no difference exists between JWZXG group and azapirones group in HAMA total score from baseline, JWZXG group was inferior to selective serotonin reuptake inhibitors (SSRIs) group (WMD −0.93, 95% CI [−1.64, −0.23]; Z test = 2.6, P = 0.009) which had more adverse events than JWZXG group (RR 0.64, 95% CI [0.46, 0.89]; Z test = 2.63, P = 0.009). Conclusions This meta-analysis preliminarily suggests that JWZXG is as effective as azapirones, though having the same possibility of suffering AEs. JWZXG was inferior to SSRIs but causes fewer AEs in the treatment of GAD.

Efficacy of Silexan in subthreshold anxiety: meta-analysis of randomised, placebo-controlled trials

Subthreshold psychiatric disorders do not fully meet the diagnostic criteria of syndromal disorders but may be associated with comparable disability. To investigate the anxiolytic effect of Silexan, an active substance from lavender oil for oral administration, in patients with subthreshold anxiety, a meta-analysis that included all published trials with Silexan in this indication was performed. Three randomised, placebo-controlled trials in subthreshold anxiety disorders (anxiety disorder not otherwise specified, restlessness and agitation, mixed anxiety and depressive disorder) were included. Eligible participants with a baseline Hamilton Anxiety Rating Scale (HAMA) total score ≥ 18 points received 1 × 80 mg/day Silexan or placebo for 10 weeks. Outcomes included the HAMA, the Pittsburgh Sleep Quality Index, the Zung Self-rating Anxiety Scale, the Clinical Global Impressions questionnaire and the SF-36 health status inventory. Data were analysed using meta-analysis based on pooled raw data of individual patients (random effects models). A total of 697 patients were assessed for efficacy. Silexan was superior to placebo in reducing the HAMA total score during 10 weeks’ treatment [mean value difference, 95% confidence interval: 3.83 (1.28; 6.37) points]. Superiority was comparably pronounced for psychic and somatic anxiety as well as for observer- and self-rated anxiety. Silexan had a beneficial effect on sleep (secondary to the anxiolytic effect) without causing sedation and improved the patients’ health-related quality of life. Adverse event incidence in both treatment groups was comparable [risk ratio: 1.06 (0.85; 1.33)]. Silexan has a significant and clinically meaningful anxiolytic effect in subthreshold anxiety. The results cannot be generalised to other lavender oil products.

Effect of Saffron (Crocus Satious L.) as an Add-On Therapy to Sertraline in Mild to Moderate Generalized Anxiety Disorder: A Double Blind Randomized Controlled Trial

Background: Generalized anxiety disorder (GAD) is known as the most prevalent anxiety disorder. Saffron has been previously approved as an effective adjuvant therapy in depression and might alleviate GAD symptoms. Methods: In the current double blind randomized controlled trial, 40 patients with mild to moderate GAD, diagnosed according to the diagnostic and statistical manual of mental disorders-V (DSM-V) and received sertraline were randomly assigned to the saffron receiving group (450 mg, n = 20) or placebo taking patients (n = 20). Interventions were administered as an add-on therapy to sertraline on a daily bases for 6 weeks. In addition to assessing anthropometric, demographic data, and dietary intakes of patients, a 14-item Hamilton anxiety rating scale (HAM-A) was used to assess the effect of treatment. Results: The mean (SD) of age was 29.65 (8.45) and 32.40 (6.74) years in the Saffron and placebo groups, respectively. Applying ANCOVA models adjusted for age, baseline energy intake, HAM-A total score, and weight changes from baseline to the 6th week, showed that at the end of the 6th week, saffron treated patients had a significantly lower mean HAM-A score compared to placebo group (2.95 vs. 5.05; P value = 0.005). Furthermore, within the group analysis it was shown that the total HAM-A score significantly declined in both groups (P value ≤ 0.000). Measuring changes in the HAM-A total score, relative to the baseline, following adjustment of ANCOVA models, showed that saffron was more effective than the placebo in reducing the mean HAM-A score of patients (-17.25 ± 2.67 vs. -15.35 ± 2.30; P value = 0.029). The side effects were tolerable and did not result in discontinuation of the supplementation. Conclusions: Saffron as a sertraline add-on therapy may attenuate GAD symptoms. However, more randomized clinical trials with a larger sample size and longer duration of follow-up are needed to confirm this effect.

Evidences of a New Psychobiotic Formulation on Body Composition and Anxiety.

Background Gut microbiota is implied in obesity, because of its ability to harvest energy from diet, and in the regulation of behavior. Given the link between gut microbiota, body composition, obesity, and anxiety, the aim of this study was to evaluate the effects of a new psychobiotic formulation. Methods Eligible patients were randomly divided into three groups: psychobiotics oral suspension group (POSG); dietary treatment group (DTG); combined treatment group (CTG). All subjects underwent body composition and psychological profile evaluation. Results Significant changes in body composition parameters in each group were relieved after all treatments. Hamilton anxiety rating scale (HAM-A) highlighted a significant reduction of the total score for all study population after treatments in POSG (p = 0.01) and CTG (p = 0.04). A reduction of HAM-A total score in anxious subjects in POSG or CTG and a significant reduction of positive subjects for HAM-A in POSG (p = 0.03) and in CDG (p = 0.01) were shown. Discussion Three-week intake of selected POS represents a good approach to solve problems related to obesity and behavior disorders. However, new clinical trials need to be performed on a larger population and for a longer period of treatment before definitive conclusions can be made. This trial is registered with NCT01890070.

Post Hoc Analyses of Anxiety Measures in Adult Patients With Generalized Anxiety Disorder Treated With Vilazodone.

ObjectiveTo investigate vilazodone, currently approved for major depressive disorder in adults, for generalized anxiety disorder (GAD).MethodThree randomized, double-blind, placebo-controlled studies showing positive results for vilazodone (2,040 mg/d) in adult patients with GAD (DSM-IV-TR) were pooled for analyses; data were collected from June 2012 to March 2014. Post hoc outcomes in the pooled intent-to-treat population (n = 1,462) included mean change from baseline to week 8 in Hamilton Anxiety Rating Scale (HARS) total score, psychic and somatic anxiety subscale scores, and individual item scores; HARS response (≥ 50% total score improvement) and remission (total score ≤ 7) at week 8; and category shifts, defined as HARS item score ≥ 2 at baseline (moderate to very severe symptoms) and score of 0 at week 8 (no symptoms).ResultsThe least squares mean difference was statistically significant for vilazodone versus placebo in change from baseline to week 8 in HARS total score (−1.83, P < .0001) and in psychic anxiety (−1.21, P < .0001) and somatic anxiety (−0.63, P < .01) subscale scores; differences from placebo were significant on 11 of 14 HARS items (P < .05). Response rates were higher with vilazodone than placebo (48% vs 39%, P < .001), as were remission rates (27% vs 21%, P < .01). The percentage of patients who shifted to no symptoms was significant for vilazodone on several items: anxious mood, tension, intellectual, depressed mood, somatic-muscular, somatic-sensory, cardiovascular, respiratory, and autonomic symptoms (P < .05).ConclusionsTreatment with vilazodone versus placebo was effective in adult GAD patients, with significant differences between treatment groups found on both psychic and somatic HARS items.Trial RegistrationClinicalTrials.gov identifiers: NCT01629966, NCT01766401, NCT01844115.

Efficacy of Silexan in mixed anxiety–depression – A randomized, placebo-controlled trial

Mixed anxiety and depressive disorder (MADD; ICD-10 F41.2) is a condition characterized by subsyndromal symptoms of anxiety and depression, neither of which are clearly predominant. Silexan has been demonstrated to be efficacious in subsyndromal and syndromal anxiety disorders and co-morbid depressive symptoms. In this study 318 adult out-patients with MADD according to ICD-10 criteria, a total score ≥18 points on the Hamilton Anxiety Rating Scale (HAMA), and at least moderately severe anxious and depressed mood were randomized and received 1×80mg Silexan or placebo in double-blind fashion for a scheduled period of 70 days. Primary outcome measures were the HAMA and Montgomery Åsberg Depression Rating Scale (MADRS) total score changes between baseline and treatment end. The HAMA total score decreased by 10.8±9.6 points for Silexan and by 8.4±8.9 points for placebo (treatment group difference: p<0.01, one-sided; ANCOVA with factors for treatment and centre and the baseline value as covariate), and total score decreases of 9.2±9.9 and 6.1±7.6 points, respectively, were observed for the MADRS (p<0.001). Compared to placebo, the patients treated with Silexan had a better over-all clinical outcome and showed more pronounced improvements of impaired daily living skills and health related quality of life. Eructation was the only adverse event with a substantially higher incidence under Silexan. The study thus demonstrates that Silexan is efficacious and safe in the treatment of MADD.

Efficacy of once-daily extended release quetiapine fumarate in patients with different levels of severity of generalized anxiety disorder

This study is a pooled, post-hoc analysis evaluating once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with generalized anxiety disorder (GAD). Three previously reported positive, 8-week, randomized, double-blind, placebo-controlled studies evaluated quetiapine XR therapy (50, 150, 300 mg/day) in patients with GAD [Hamilton Anxiety Rating Scale (HAM-A) total score ≥ 20]. Patients were stratified by baseline severity: HAM-A total score ≥ 22, ≥ 24, < 26, ≥ 26, ≥ 28. We report HAM-A total score change, response (≥ 50% reduction in HAM-A total score), and remission (HAM-A total score ≤ 7 and ≤ 9). Quetiapine XR significantly improved HAM-A total scores compared with placebo at Weeks 1 and 8 in the HAM-A ≥ 22, ≥ 24, and ≥ 26 cohorts (all doses), at Week 1 (all doses) and Week 8 (quetiapine XR 150 mg/day) in the < 26 cohort, and at Week 1 (all doses) and Week 8 (quetiapine XR 50 and 150 mg/day) in the HAM-A ≥ 28 group (P<0.05). Week 8 effect sizes for 50, 150, and 300 mg/day were as follows: 0.29, 0.47, 0.17 (HAM-A ≥ 22); 0.35, 0.55, 0.22 (HAM-A ≥ 24); 0.18, 0.32, 0.10 (HAM-A < 26); 0.41, 0.59, 0.24 (HAM-A ≥ 26); 0.60, 0.64, 0.22 (HAM-A ≥ 28), respectively. Acute quetiapine XR monotherapy significantly improves anxiety compared with placebo in patients with moderate or severe GAD, with symptom improvements seen as early as Week 1.

Efficacy and safety of duloxetine in the treatment of older adult patients with generalized anxiety disorder: a randomized, double‐blind, placebo‐controlled trial

ObjectiveThis was a flexible-dosed study to evaluate the efficacy and safety of duloxetine 30–120 mg once daily in the treatment of generalized anxiety disorder (GAD) in older adult patients.MethodsPatients with GAD, who were at least 65 years of age, were randomly assigned to double-blind treatment with either duloxetine (N = 151) or placebo (N = 140). The primary efficacy measure was the Hamilton Anxiety Rating Scale (HAM-A) total score, and the primary endpoint was at week 10. Global functioning was assessed by the Sheehan Disability Scale (SDS). Safety and tolerability was assessed by the occurrence of treatment-emergent adverse events, serious adverse events, laboratory analyses, and vital signs. Analyses were conducted on an intent-to-treat basis.ResultsThe overall baseline mean HAM-A total score was 24, and SDS global score was 14. Completion rates were 75% for placebo and 76% for duloxetine. At week 10, duloxetine was superior to placebo on mean changes from baseline in HAM-A total scores (−15.9 vs. −11.7, p < 0.001) and in SDS global scores (−8.6 vs. −5.4, p < 0.001). Treatment-emergent adverse events occurred in ≥5% of duloxetine-treated patients and twice the rate than with placebo including constipation (9% vs. 4%, p = 0.06), dry mouth (7% vs. 1%, p = 0.02), and somnolence (6% vs. 2%, p = 0.14).ConclusionDuloxetine treatment was efficacious in the improvement of anxiety and functioning in older adult patients with GAD, and the safety profile was consistent with previous GAD studies. © 2014 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd.Key pointsTreatment with duloxetine versus placebo can significantly reduce symptoms of generalized anxiety disorder and was associated with improved global function and increased enjoyment and satisfaction with life in patients 65 years and older.The safety and tolerability profile for duloxetine in this older adult patient population was consistent with the established profile for treatment of generalized anxiety disorder in the broader mostly younger (≥18 years of age) population, and there were no new safety findings.