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Abstract: Background: It is widely believed that in randomized controlled trials of antidepressants the difference between drug and placebo response rates is rather small (around 20%), leading to a common perception that antidepressants have limited efficacy. Aim: The aim of the present paper was to present an alternative calculation and interpretation of antidepressant–placebo difference in the treatment response to antidepressant in drug trials which may shed a new light on the efficacy of antidepressants. Issues: We have previously highlighted several controversial points concerning the calculation of antidepressant and placebo response rates in randomised controlled trials, which may influence views concerning the efficacy of drugs, and demonstrated several factors which may lead to overestimation of the placebo effect and underestimation of antidepressant efficacy. The traditional interpretation of antidepressant–placebo difference in randomized controlled trials on major depression has been also challenged previously from at least five points of view but all leading to a conclusion that currently prevailing opinions concerning relative placebo and antidepressant response rates overestimate placebo response, and thereby underestimate efficacy of antidepressant drugs. In our present paper we propose another method for calculating placebo and antidepressant response rates which may shed new light on an overlooked aspect of the efficacy of these drugs. Conclusions: We contend that opinions on the effectiveness of antidepressants should be reconsidered, and comparisons with placebo should be more carefully applied. Interpretation of the placebo response is of crucial importance for establishing the efficacy of antidepressive medications, and psychiatry should not become the hostage of placebo. [Copyright &y& Elsevier]

Background: In epidemiological studies, statins appear to benefit mood, and there are now some randomized controlled trials examining the efficacy of statins. However, the role of statins in depression remains uncertain. Thus the aim of this paper was to assess the effect of statins on depressive symptoms by performing a meta-analysis of all double-blind, randomized, placebo controlled clinical trials (RCT) conducted in subjects with depression.Methods: A systematic search was executed using PubMed and ClinicalTrials.gov in November 30th, 2015 for all double-blind, RCT of statins versus placebo in persons with depressive symptoms. Sixty-seven potential articles were identified through search of electronic databases, of those three met inclusion criteria and were included in the meta-analysis. The outcome measure was change in Hamilton Depression Rating Scale (HDRS) scores associated with statin use. A meta-analysis was conducted and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. GRADE was used to assess study quality.Results: The three articles included provided data on 165 participants with moderate to severe depression. Of these, 82 were randomized to statins as an adjuvant therapy to antidepressant treatment (i.e., citalopram or fluoxetine) and 83 to the placebo arm. All studies were double-blind RCTs, with a follow-up of 6-12 weeks. The statin agents evaluated were lovastatin, atorvastatin, and simvastatin. When compared to placebo, statins, as add-on to treatment as usual, largely improved depressive symptoms as assessed by the HDRS (SMD=-0.73, 95% IC -1.04 to -0.42, p<0.001, 3 between-group comparisons, n=165). No serious adverse effects were reported.Conclusions: Our results suggest that adjunctive treatment with statins could be useful for the treatment of depressive symptoms. Additional double-blind, randomised, placebo-controlled trials are necessary to settle the matter. [ABSTRACT FROM AUTHOR]

Background Depressive and anxiety disorders contribute to a high disease burden. This paper investigates whether concise formats of cognitive behavioral- and/or pharmacotherapy are equivalent with longer standard care in the treatment of depressive and/or anxiety disorders in secondary mental health care. Methods A pragmatic randomized controlled equivalence trial was conducted at five Dutch outpatient Mental Healthcare Centers (MHCs) of the Regional Mental Health Provider (RMHP) ‘Rivierduinen’. Patients (aged 18–65 years) with a mild to moderate anxiety and/or depressive disorder, were randomly allocated to concise or standard care. Data were collected at baseline, 3, 6 and 12 months by Routine Outcome Monitoring (ROM). Primary outcomes were the Brief Symptom Inventory (BSI) and the Web Screening Questionnaire (WSQ). We used Generalized Estimating Equations (GEE) to assess outcomes. Results Between March 2010 and December 2012, 182 patients, were enrolled ( n = 89 standard care; n = 93 concise care). Both intention-to-treat and per-protocol analyses demonstrated equivalence of concise care and standard care at all time points. Severity of illness reduced, and both treatments improved patient’s general health status and subdomains of quality of life. Moreover, in concise care, the beneficial effects started earlier. Discussion Concise care has the potential to be a feasible and promising alternative to longer standard secondary mental health care in the treatment of outpatients with a mild to moderate depressive and/or anxiety disorder. For future research, we recommend adhering more strictly to the concise treatment protocols to further explore the beneficial effects of the concise treatment. The study is registered in the Netherlands Trial Register, number NTR2590. Clinicaltrials.gov identifier: NCT01643642 . [ABSTRACT FROM AUTHOR]

Objective Low-grade chronic inflammation is one potential mechanism underlying the well-established association between major depressive disorder (MDD) and increased cardiovascular morbidity. Both aspirin and statins have anti-inflammatory properties, which may contribute to their preventive effect on cardiovascular diseases. Previous studies on the potentially preventive effect of these drugs on depression have provided inconsistent results. The aim of the present paper was to assess the prospective association between regular aspirin or statin use and the incidence of MDD. Method This prospective cohort study included 1631 subjects (43.6% women, mean age 51.7 years), randomly selected from the general population of an urban area. Subjects underwent a thorough physical evaluation as well as semi-structured interviews investigating DSM-IV mental disorders at baseline and follow-up (mean duration 5.2 years). Analyses were adjusted for a wide array of potential confounders. Results Our main finding was that regular aspirin or statin use at baseline did not reduce the incidence of MDD during follow-up, regardless of sex or age (hazard ratios, aspirin: 1.19; 95%CI, 0.68–2.08; and statins: 1.25; 95%CI, 0.73–2.14; respectively). Limitations Our study is not a randomized clinical trial and could not adjust for all potential confounding factors, information on aspirin or statin use was collected only for the 6 months prior to the evaluations, and the sample was restricted to subjects between 35 and 66 years of age. Conclusion Our data do not support a large scale preventive treatment of depression using aspirin or statins in subjects aged from 35 to 66 years from the community. [ABSTRACT FROM AUTHOR]

Background: As yet there is no firm evidence about the types of intervention that can reduce emergency room revisits. However, the literature on emergency room revisits suggests patient difficulties with managing their health problems and treatments after discharge may play a role. Objectives: We carried out a randomized trial of an emergency department-based nursing intervention, but results showed no reduction in revisits (primary outcome). This paper describes the secondary outcomes of the trial: patient perceptions of continuity of care, illness perceptions, self-care capacities, psychological symptoms and medication adherence 30 days after emergency room discharge. Design: Randomized, controlled trial. Settings: The trial was conducted in the emergency department of a tertiary cardiac hospital in Montreal, Canada between November 2007 and March 2010. Participants: The study involved 203 patients, including 108 in the experimental group and 95 in the control group. Methods: The intervention included one nurse patient encounter before discharge and two phone calls in the 10 days after discharge. Participants provided data 30 days post-discharge on secondary outcomes potentially related to emergency department revisits. Results: Although, as previously reported, the intervention had no impact on the primary outcome of emergency department revisits, the present study demonstrated a significant positive effect on patients’ perceived continuity of care (p = .033), self-care capacities (p = .037), anxiety (p = .007) and depressive symptoms (p = .043), and the illness perceptions treatment control subscale (p = .037). No differences were found for other illness perception subscales or medication adherence (all p’s > .05). Conclusion: Although the intervention did not influence emergency department revisits it did improve secondary outcomes, suggesting pathways for future research. [ABSTRACT FROM AUTHOR]

Shugan granule is derived from Xiaoyao powder, a traditional Chinese medicine that has been shown to be effective in treating emotional disorders. At present, there is no standard drug treatment for mixed anxiety-depressive disorder (MADD), and no evidence-based clinical trial has been performed for any drug, meaning MADD patients are unable to obtain standardized treatment. The purpose of this clinical trial was to test the clinical efficacy and safety of Shugan granules in the treatment of MADD, and to provide clinical trial-based support along with drug recommendations for the treatment of MADD. A multicenter, randomized, double-blind, placebo-controlled study was conducted on 400 patients with MADD recruited from January 1, 2019 to December 31, 2020, and they were randomly divided into test and placebo groups with a 1:1 ratio. Subjects in the test group (n = 200) received oral administration of Shugan granules, while subjects in the placebo group (n = 200) received oral administration of a Shugan granule simulator. The treatment lasted for 8 weeks. The Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale-17 (HAMD-17), Clinical Global Impression Scale (CGIS), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used to evaluate efficacy. In addition, the traditional Chinese medicine (TCM) syndrome scale for MADD was developed to observe improvements of related symptoms in patients after treatment based on the disease guidelines of TCM and the clinical manifestations of depression. Furthermore, the safety of Shugan granules was evaluated during and after treatment. After 8 weeks of treatment, the total scores for HAMA, HAMD, SAS, and SDS in the test group were significantly lower than those in the placebo group (P < 0.01). The proportion of patients with efficacy index (EI) > 1 for the CGIS score in the test group was significantly higher than that in the placebo group (P < 0.01). The efficacy of treatment in the test group based on the TCM syndrome scale was 70.16% and 88.27% after 4 weeks and 8 weeks, respectively, which was significantly higher than that in the placebo group (44.27% and 66.67% after 4 weeks and 8 weeks, respectively; P < 0.01). The disappearance rate of single symptoms in the test group was 20–30% higher than that in the placebo group, with a significant difference between groups (P < 0.05). During the treatment period, the incidence of adverse reactions was 2.05% in the test group and 2.06% in the placebo group, with no significant differences noted (P = 1.0000). Shugan granule was more effective than placebo in the treatment of MADD. Moreover, there was no significant difference between the two groups in terms of safety. This paper provides a clinical therapeutic regime using Shugan granule for the treatment of MADD. [Display omitted] • As far as we know, this is the first randomized controlled multicenter clinical trial for MADD in the world. • The indications for usage of Xiaoyao powder was expanded to the treatment or control of MADD. • We developed the TCM symptom scale for evaluation of MADD and therapeutic effects of medications on it. • This study provides a high-quality evidence for the treatment of MADD by using a standardized traditional formula". [ABSTRACT FROM AUTHOR]

Abstract: Most comparisons of the efficacy of antidepressants have relied on the assumption that missing data are randomly distributed. Dropout rates differ between drugs, suggesting this assumption may not hold true. This paper examines the effect of non-random dropout on a comparison of two antidepressant drugs, escitalopram and nortriptyline, in the treatment of major depressive disorder. The GENDEP study followed adult patients with major depressive disorder over 12 weeks of treatment, and the primary analysis found no difference in efficacy of the two antidepressants under missing at random assumption. By applying the recently developed Muthén–Roy model, we compared the relative efficacy of these two antidepressants taking into account non-random distribution of missing outcomes (NMAR). Individuals who dropped out of the study were those who were not responding to treatment. Based on the best fitting NMAR model, it was found that escitalopram reduced symptom scores by an additional 1.4 points on the Montgomery–Åsberg Depression Rating Scale (p = 0.02), equivalent to 5% of baseline depression severity, compared to nortriptyline. We conclude that association between dropout and worsening symptoms led to an overestimate of the effectiveness of treatment, especially with nortriptyline, in the primary analysis. These findings review the primary analysis of GENDEP and suggest that, when non-random dropout is accounted for, escitalopram is more effective than nortriptyline in reducing symptoms of major depression. [Copyright &y& Elsevier]

Abstract: This paper describes the rationale and design of the vanguard for the Comparison of Depression Interventions after Acute Coronary Syndrome (CODIACS), a multicenter, randomized, controlled trial of a patient preference‐based, stepped care protocol for persistent depressive symptoms after acute coronary syndrome (ACS). The overall aim of the vanguard phase was to determine whether the patient-preference, stepped care protocol, which is based on the intervention used in the recent Coronary Psychosocial Evaluation Studies (COPES) trial, was feasible in patients with recent ACS who were recruited from 5 geographically diverse sites. Innovative design features of this trial include randomization to either initial patient-preference of treatment or to a referred care arm in which the primary care provider decided upon care. Additionally, delivery of psychotherapy was accomplished by telephone, or webcam, depending upon patient preference. The vanguard phase provides estimates of eligibility and screening/enrollment ratios, patient acceptance of screening, and retention. In this report, we describe the innovative features and the baseline results of the vanguard phase of CODIACS. The data from this vanguard study will be used to finalize planning for a large, phase III clinical trial designed to evaluate the effect of treatment on depressive symptoms, coronary events, and death. [Copyright &y& Elsevier]

Abstract: Aim of study: Depression is a psychiatric disorder. Chaihu-Shugan-San (CSS) is a traditional Chinese medicine formula suggested in the treatment of depression, but its effectiveness and safety are not well defined. This meta-analysis aimed to assess the effectiveness and safety of CSS in depression therapy. Materials and methods: The databases including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CNKI database, Wanfang Data and VIP Information were searched. Papers were reviewed systematically by two researchers and were analyzed using Cochrane software Revman 5.0. Results: Ten randomized controlled trials comparing 835 subjects were included. Of these studies, seven studies used fluoxetine (20mg, once a day), two used paroxetine (20mg, once a day) and one used doxepin (25mg, two times a day) as the antidepressant drugs. Meta-analyses revealed that CSS in combination with antidepressant drugs treatment significantly improved depressive symptoms (WMD=−3.56; 95% CI −5.09 to −2.03) and significantly increased effective rate (OR=3.31; 95% CI 1.80–6.10) and recovery rate (OR=2.32; 95% CI 1.61–3.34) compared with antidepressant drugs therapy. In addition, the efficacy of CSS as monotherapy was significantly better than antidepressants in improving depressive symptoms (WMD=−3.09; 95% CI −5.13 to −1.06) and in creasing effective rate (OR=2.61; 95% CI 1.23–5.53). CSS was comparable to antidepressants in increasing recovery rate (OR=1.83; 95% CI 0.84–3.98). No serious adverse events were reported in any of the included trials. Conclusion: The present work supported that CSS was effective and safe in treating depressed patients. More full-scale randomized clinical trials with reliable designs are recommended to further evaluate the clinical benefit and long-term effectiveness of CSS for the treatment of depression. [Copyright &y& Elsevier]

Abstract: Background: Antidepressants are often the first-line treatment for depression but only one third of patients respond fully to pharmacotherapy. This paper describes the protocol for a randomised controlled trial (RCT) designed to evaluate the clinical and cost effectiveness of cognitive behavioural therapy (CBT) as an adjunct to pharmacotherapy for patients with treatment resistant depression in primary care. Methods/design: CoBalT is a two parallel group multi-centre pragmatic RCT. Eligible participants were those who: (i) were aged 18–75years; (ii) were currently taking antidepressant medication (for at least 6weeks at an adequate dose); (iii) scored ≥14 on the Beck Depression Inventory (BDI-II); (iv) had adhered to their medication; and (v) met ICD-10 criteria for depression (assessed using the Clinical Interview Schedule — revised version). Those who gave written informed consent were randomised to one of two treatment groups: usual care or usual care plus CBT. The primary outcome is depressive symptoms assessed using the BDI-II at 6months post-randomisation. Secondary outcomes measured at 6 and 12months include quality of life, antidepressant use and health care utilisation. Outcomes will be analysed on an intention-to-treat basis. Discussion: The CoBalT trial will provide evidence on the clinical and cost effectiveness of CBT as an adjunct to antidepressant medication in the treatment of depression that has not responded to pharmacotherapy. Given the move to widen access to ‘talking therapies’, the results of this study will be timely. [Copyright &y& Elsevier]

Abstract: Objective: To review the efficacy of non-pharmacological treatment for depression in people with depression and chronic physical health problems. Method: Five electronic databases were searched including EMBASE, Medline and PsycINFO for randomized controlled trials (RCTs). Each paper was assessed for quality, data extracted and, where possible, the data meta-analyzed. The overall quality of each meta-analysis was assessed. Results: 35 studies met our inclusion criteria and 22 were meta-analyzed using a random-effects model. The largest and strongest evidence base supports individual- and group-based cognitive and behavioral interventions (18 trials). The evidence was strongest for those interventions aimed solely at reducing depression in comparison to those aimed more broadly at reducing the psychosocial stress associated with having a chronic physical health problem. Conclusion: Overall, the efficacy of certain types of non-pharmacological interventions for people with depression and chronic physical health problems has been demonstrated. The overall impression is that their efficacy in this population is comparable to that in people with depression without chronic physical health problems but the evidence-base is currently inadequate and larger trials with long-term follow-up are required. [Copyright &y& Elsevier]

Abstract: Sickness leave is a major source of societal costs in depression treatment. However, very little is known about the rationale behind sick leave and their effects on depressive symptoms. Aim of the paper is to evaluate the effect of sick leave on treatment outcome and the association of sick leave with patient, depression and treatment-related factors. For this we compared patients with sick leave and non-sick leave regarding symptom reduction following 6weeks of treatment. A total of 118 patients of 41 physicians in a controlled clinical trial with a naturalistic prospective design were analysed. After 8weeks of treatment no significant differences were found between patients who had or did not have sick leave, in terms of improvement of depressive symptoms. The analyses of physician, patient and illness-related variables regarding their predictive value showed no significant effect. No systematic effect of sick leave and no clear criteria were found that were related to receiving a sick leave certificate. It can be assumed that physicians do not only base the decision of whether to sign a depressive patient off sick on illness-specific factors. For a targeted implementation of sick leave as therapeutic measure predictors for effectiveness should be defined. [ABSTRACT FROM AUTHOR]

Abstract: This paper describes the context in which a theoretically driven physical activity counselling intervention was developed as a pragmatic treatment for primary care patients with depression. The intervention, delivered by Physical Activity Facilitators (PAFs), alongside usual care, was developed and piloted, then compared with usual care within a randomised TRial of Exercise and Depression in the UK (TREAD-UK). Details about the background of the intervention are provided, including underpinning principles, theoretical framework (i.e., Self-Determination Theory; ) for behaviour change, counselling style and techniques (drawn mainly from motivational interviewing), contextual issues, and delivery issues associated with the PAF. In particular, we provide an outline of the content of a training programme for the PAFs. A detailed description of how we operationalised the intervention including aims, content and techniques, and strategies employed by the PAFs is provided. Finally, we reflect on future implementation issues. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cognitive therapy (CT) has been shown to be efficacious in the treatment of depression in numerous randomized controlled trials (RCTs). However, little evidence is available that speaks to the effectiveness of this treatment under routine clinical conditions. Method: This paper examines outcomes of depressed individuals seeking cognitive therapy at an outpatient clinic (N =217, Center for Cognitive Therapy; CCT). Outcomes were then compared to those of participants in a large NIMH-funded RCT of cognitive therapy and medications as treatments for depression. Results: The CCT is shown to be a clinically representative setting, and 61% of participants experienced reliable change in symptoms over the course of treatment; of those, 45% (36% of the total sample) met criteria for recovery by the end of treatment. Participants at CCT had similar outcomes to participants treated in the RCT, but there was some evidence that those with more severe symptoms at intake demonstrated greater improvement in the RCT than their counterparts at CCT. Limitations: The CCT may not be representative of all outpatient settings, and the structure of treatment there was considerably different from that in the RCT. Treatment fidelity was not assessed at CCT. Conclusions: Depressed individuals treated with cognitive therapy in a routine clinical care setting showed a significant improvement in symptoms. When compared with outcomes evidenced in RCTs, there was little evidence of superior outcomes in either setting. However, for more severe participants, outcomes were found to be superior when treatment was delivered within an RCT than in an outpatient setting. Clinicians treating such patients in non-research settings may thus benefit from making modifications to treatment protocols to more closely resemble research settings. [ABSTRACT FROM AUTHOR]