The sustained psychological impact of coronavirus disease 2019 pandemic on hospital workers 2 years after the outbreak: a repeated cross-sectional study in Kobe.

BACKGROUND: Healthcare workers who are exposed to coronavirus disease 2019 are psychologically distressed. This study aimed to evaluate the mental health outcomes of hospital workers 2 years after the outbreak of coronavirus disease 2019 and to identify changes in the stress of hospital workers and predicted risk factors. METHODS: This survey was conducted 2 years after the initial evaluation performed under the first emergency declaration of the coronavirus disease 2019 pandemic among hospital workers at the same hospital in an ordinance-designated city in Japan from June to July 2022. Sociodemographic data, 19 stress-related question responses, the Impact of Event Scale-Revised, and the Maslach burnout inventory-general survey were collected. Multiple regression models were used to identify factors associated with each of the mental health outcomes 2 years after the coronavirus disease 2019 outbreak. RESULTS: We received 719 valid responses. Between 2020 and 2022, hospital workers' anxiety about infection decreased, whereas their exhaustion and workload increased. Multiple regression analysis revealed that 2 years after the coronavirus disease 2019 outbreak, nurses and young people were at a higher risk of experiencing stress and burnout due to emotional exhaustion, respectively. CONCLUSIONS: This is the first study to examine the long-term stress of hospital workers measured in Japan. Exhaustion and workload were worsened 2 years into the pandemic. Therefore, health and medical institutions should continuously monitor the physical and psychological health of staff members.

Pharmacological treatments in panic disorder in adults: a network meta-analysis.

BACKGROUND: A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines. OBJECTIVES: To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses. MAIN RESULTS: Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low. AUTHORS' CONCLUSIONS: In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.

The Impact of the COVID-19 Pandemic and Associated Control Measures on the Mental Health of the General Population : A Systematic Review and Dose-Response Meta-analysis.

BACKGROUND: To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. PURPOSE: To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose-response relations with characteristics of the pandemic and its containment. DATA SOURCES: Relevant articles were identified from the living evidence database of the COVID-19 Open Access Project, which indexes COVID-19-related publications from MEDLINE via PubMed, Embase via Ovid, and PsycInfo. Preprint publications were not considered. STUDY SELECTION: Longitudinal studies that reported data on the general population's mental health using validated scales and that were published before 31 March 2021 were eligible. DATA EXTRACTION: An international crowd of 109 trained reviewers screened references and extracted study characteristics, participant characteristics, and symptom scores at each timepoint. Data were also included for the following country-specific variables: days since the first case of SARS-CoV-2 infection, the stringency of governmental containment measures, and the cumulative numbers of cases and deaths. DATA SYNTHESIS: In a total of 43 studies (331 628 participants), changes in symptoms of psychological distress, sleep disturbances, and mental well-being varied substantially across studies. On average, depression and anxiety symptoms worsened in the first 2 months of the pandemic (standardized mean difference at 60 days, -0.39 [95% credible interval, -0.76 to -0.03]); thereafter, the trajectories were heterogeneous. There was a linear association of worsening depression and anxiety with increasing numbers of reported cases of SARS-CoV-2 infection and increasing stringency in governmental measures. Gender, age, country, deprivation, inequalities, risk of bias, and study design did not modify these associations. LIMITATIONS: The certainty of the evidence was low because of the high risk of bias in included studies and the large amount of heterogeneity. Stringency measures and surges in cases were strongly correlated and changed over time. The observed associations should not be interpreted as causal relationships. CONCLUSION: Although an initial increase in average symptoms of depression and anxiety and an association between higher numbers of reported cases and more stringent measures were found, changes in mental health symptoms varied substantially across studies after the first 2 months of the pandemic. This suggests that different populations responded differently to the psychological stress generated by the pandemic and its containment measures. PRIMARY FUNDING SOURCE: Swiss National Science Foundation. (PROSPERO: CRD42020180049).

Discontinuation of antidepressants after remission with antidepressant medication in major depressive disorder: a systematic review and meta-analysis.

A significant clinical issue encountered after a successful acute major depressive disorder (MDD) treatment is the relapse of depressive symptoms. Although continuing maintenance therapy with antidepressants is generally recommended, there is no established protocol on whether or not it is necessary to prescribe the antidepressant used to achieve remission. In this meta-analysis, the risk of relapse and treatment failure when either continuing with the same drug used to achieved remission or switching to a placebo was assessed in several clinically significant subgroups. The pooled odds ratio (OR) (±95% confidence intervals (CI)) was calculated using a random effects model. Across 40 studies (n = 8890), the relapse rate was significantly lower in the antidepressant group than the placebo group by about 20% (OR = 0.38, CI: 0.33-0.43, p < 0.00001; 20.9% vs 39.7%). The difference in the relapse rate between the antidepressant and placebo groups was greater for tricyclics (25.3%; OR = 0.30, CI: 0.17-0.50, p < 0.00001), SSRIs (21.8%; OR = 0.33, CI: 0.28-0.38, p < 0.00001), and other newer agents (16.0%; OR = 0.44, CI: 0.36-0.54, p < 0.00001) in that order, while the effect size of acceptability was greater for SSRIs than for other antidepressants. A flexible dose schedule (OR = 0.30, CI: 0.23-0.48, p < 0.00001) had a greater effect size than a fixed dose (OR = 0.41, CI: 0.36-0.48, p < 0.00001) in comparison to placebo. Even in studies assigned after continuous treatment for more than 6 months after remission, the continued use of antidepressants had a lower relapse rate than the use of a placebo (OR = 0.40, CI: 0.29-0.55, p < 0.00001; 20.2% vs 37.2%). The difference in relapse rate was similar from a maintenance period of 6 months (OR = 0.41, CI: 0.35-0.48, p < 0.00001; 19.6% vs 37.6%) to over 1 year (OR = 0.35, CI: 0.29-0.41, p < 0.00001; 19.9% vs 39.8%). The all-cause dropout of antidepressant and placebo groups was 43% and 58%, respectively, (OR = 0.47, CI: 0.40-0.55, p < 0.00001). The tolerability rate was ~4% for both groups. The rate of relapse (OR = 0.32, CI: 0.18-0.64, p = 0.0010, 41.0% vs 66.7%) and all-cause dropout among adolescents was higher than in adults. To prevent relapse and treatment failure, maintenance therapy, and careful attention for at least 6 months after remission is recommended. SSRIs are well-balanced agents, and flexible dose adjustments are more effective for relapse prevention.

Unguided Computer-Assisted Self-Help Interventions Without Human Contact in Patients With Obsessive-Compulsive Disorder: Systematic Review and Meta-analysis.

BACKGROUND: Computer-assisted treatment may reduce therapist contact and costs and promote client participation. This meta-analysis examined the efficacy and acceptability of an unguided computer-assisted therapy in patients with obsessive-compulsive disorder (OCD) compared with a waiting list or attention placebo. OBJECTIVE: This study aimed to evaluate the effectiveness and adherence of computer-assisted self-help treatment without human contact in patients with OCD using a systematic review and meta-analysis approach. METHODS: Randomized controlled trials with participants primarily diagnosed with OCD by health professionals with clinically significant OCD symptoms as measured with validated scales were included. The interventions included self-help treatment through the internet, computers, and smartphones. We excluded interventions that used human contact. We conducted a search on PubMed, Cochrane Central Register of Controlled Trials, EMBASE, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov, as well as the reference lists of the included studies. The risk of bias was evaluated using version 2 of the Cochrane risk-of-bias tool for randomized trials. We calculated the standardized mean differences for continuous outcomes and risk ratios for dichotomous outcomes. The primary outcomes were short-term improvement of OCD symptoms measured by validated scales and dropout for any reason. RESULTS: We included 11 randomized controlled trials with a total of 983 participants. The results indicated that unguided computer-assisted self-help therapy was significantly more effective than a waiting list or psychological placebo (standard mean difference -0.47, 95% CI -0.73 to -0.22). Unguided computer-assisted self-help therapy had more dropouts for any reason than waiting list or psychological placebo (risk ratio 1.98, 95% CI 1.21 to 3.23). However, the quality of evidence was very low because of the risk of bias and inconsistent results among the included studies. The subgroup analysis showed that exposure response and prevention and an intervention duration of more than 4 weeks strengthen the efficacy without worsening acceptability. Only a few studies have examined the interaction between participants and systems, and no study has used gamification. Most researchers only used text-based interventions, and no study has used a mobile device. The overall risk of bias of the included studies was high and the heterogeneity of results was moderate to considerable. CONCLUSIONS: Unguided computer-assisted self-help therapy for OCD is effective compared with waiting lists or psychological placebo. An exposure response and prevention component and intervention duration of more than 4 weeks may strengthen the efficacy without worsening the acceptability of the therapy. TRIAL REGISTRATION: PROSPERO (International Prospective Register of Systematic Reviews) CRD42021264644; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=264644.

Comparing methods for estimating patient-specific treatment effects in individual patient data meta-analysis.

Meta-analysis of individual patient data (IPD) is increasingly used to synthesize data from multiple trials. IPD meta-analysis offers several advantages over meta-analyzing aggregate data, including the capacity to individualize treatment recommendations. Trials usually collect information on many patient characteristics. Some of these covariates may strongly interact with treatment (and thus be associated with treatment effect modification) while others may have little effect. It is currently unclear whether a systematic approach to the selection of treatment-covariate interactions in an IPD meta-analysis can lead to better estimates of patient-specific treatment effects. We aimed to answer this question by comparing in simulations the standard approach to IPD meta-analysis (no variable selection, all treatment-covariate interactions included in the model) with six alternative methods: stepwise regression, and five regression methods that perform shrinkage on treatment-covariate interactions, that is, least absolute shrinkage and selection operator (LASSO), ridge, adaptive LASSO, Bayesian LASSO, and stochastic search variable selection. Exploring a range of scenarios, we found that shrinkage methods performed well for both continuous and dichotomous outcomes, for a variety of settings. In most scenarios, these methods gave lower mean squared error of the patient-specific treatment effect as compared with the standard approach and stepwise regression. We illustrate the application of these methods in two datasets from cardiology and psychiatry. We recommend that future IPD meta-analysis that aim to estimate patient-specific treatment effects using multiple effect modifiers should use shrinkage methods, whereas stepwise regression should be avoided.

Melancholic features (DSM-IV) predict but do not moderate response to antidepressants in major depression: an individual participant data meta-analysis of 1219 patients.

It is sometimes clinically believed that major depression with melancholic features is more responsive to antidepressants than non-melancholic depression. Proper analysis and, therefore, valid evidence to support or refute this common clinical lore is lacking. The sample was taken from three placebo-controlled randomized trials of duloxetine, escitalopram and paroxetine (n = 1219). We conducted a two-step individual participant data meta-analysis to combine linear mixed-effects regressions modeling melancholic features as prognostic factor (variable that predicts overall response regardless of the treatments) and as effect modifier (variable that predict differential response to drug over placebo). Melancholic features represented a statistically significant prognostic factor for greater reduction in depression severity both on antidepressants and on placebo, especially after 4 weeks of treatment. However, they were not an effect modifier of the antidepressant treatment through the acute phase treatment: in other words. The superiority of antidepressants over placebo was not influenced by the melancholic features. The treatment decision-making as to the benefits of antidepressant treatment for patients with major depression should not be influenced by the presence or absence of melancholic features.

The Characteristics and Social Functioning of Pathological Social Withdrawal, "Hikikomori," in a Secondary Care Setting: a One-Year Cohort Study.

BACKGROUND: Pathological social withdrawal, named "Hikikomori," is a Japanese culture-bound syndrome and a serious social problem in Japan. The number of Hikikomori cases in Japan was estimated at about 563,000 in 2016 according to governmental surveys. However, no studies have reported how many people with Hikikomori have access to community-based psychiatry clinics, and how different they are from non-Hikikomori patients regarding their baseline characteristics and outcomes. The aim of the present study is to evaluate the baseline characteristics, clinical attendance, and social functioning of community psychiatric clinic patients treated for social withdrawal at one-year follow-up. METHOD: Participants (n = 304) were all patients (aged under 65) of a psychiatric clinic in a one-year period. Baseline patient characteristics were compared among "current" Hikikomori patients, "past" Hikikomori," and "other" patients. Logistic regression analysis of clinic attendance status and social functioning at one-year follow-up was used to assess patient outcomes. Independent variables were age, gender, Hikikomori status, and support from clinical staff. RESULTS: Numbers of "current", "past" Hikikomori, and "other" patients were 60 (19.7%), 81 (26.6%), and 163 (53.6%), respectively. The percentage of "current" Hikikomori who attended in person (56.7%) was significantly smaller than for "past" (92.6%) and "other" (92.6) (p < .001). The age distribution of "current" Hikikomori patients was bimodal, peaking at 20 and 40-45 years. The "current" state predicted significantly fewer regular visits (OR = 0.43; 95% CI = 0.22-0.83; p = .012); support from psychiatric social workers increased visits (OR = 2.35; 95% CI = 1.14-4.86; p = .021). Among the "current" Hikikomori patients, first visit attendance in person predicted regular attendance; no factor consistently predicted working/schooling status. CONCLUSION: A sizable percentage of community clinic patients experienced Hikikomori. The "current" Hikikomori state corresponded with low clinic attendance and social function; "support from clinical staff" may increase visit regularity; no factors consistently improved social functioning. Further multi-site study is warranted to examine the generalizability of the findings from the current single-center study.

Proton pump inhibitors for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common and progressive disease characterised by chronic cough, airflow limitation and recurrent exacerbations. Since COPD exacerbations are linked to rising mortality and reduced quality of life, the condition poses a substantial burden on individuals, society and the healthcare system. Effective management of COPD exacerbations that includes treatment of related conditions in people with COPD is thus recognised as a relevant clinical question and an important research topic. Gastroesophageal reflux disease (GERD) is a known comorbidity of COPD, and pulmonary microaspiration of gastric acid is thought to be a possible cause of COPD exacerbations. Therefore, reducing gastric acid secretion may lead to a reduction in COPD exacerbations. Proton pump inhibitors (PPIs) are one of the most commonly prescribed medications and are recommended as first-line therapy for people with GERD because of their inhibitory effects on gastric acid secretion. Treatment with PPIs may present a viable treatment option for people with COPD. OBJECTIVES: To evaluate the efficacy and safety of PPI administration for people with COPD, focusing on COPD-specific outcomes. SEARCH METHODS: We searched the Cochrane Airways Register of Trials and conventional clinical trial registers from inception to 22 May 2020. We also screened bibliographies of relevant studies. SELECTION CRITERIA: Parallel-group and cluster-randomised controlled trials (RCTs) that compared oral PPIs versus placebo, usual care or low-dose PPIs in adults with COPD were eligible for inclusion. We excluded cross-over RCTs, as well as studies with a duration of less than two months. DATA COLLECTION AND ANALYSIS: Two independent review authors screened search results, selected studies for inclusion, extracted study characteristics and outcome data, and assessed risk of bias according to standard Cochrane methodology. We resolved discrepancies by involving a third review author. Primary outcomes of interest were COPD exacerbations, pneumonia and other serious adverse events. Secondary outcomes were quality of life, lung function test indices, acute respiratory infections and disease-specific adverse events. We extracted data on these outcome measures and entered into them into Review Manager software for analysis. MAIN RESULTS: The search identified 99 records, and we included one multicentre RCT that randomised 103 adults with COPD. The 12-month RCT compared an oral PPI (lansoprazole) and usual care versus usual care alone. It was conducted at one tertiary care hospital and three secondary care hospitals in Japan. This study recruited participants with a mean age of 75 years, and excluded people with symptoms or history of GERD. No placebo was used in the usual care arm. Among the primary and secondary outcomes of this review, the study only reported data on COPD exacerbations and acute respiratory infections (the common cold). As we only included one study, we could not conduct a meta-analysis. The included study reported that 12 of the 50 people on lansoprazole had at least one exacerbation over a year, compared to 26 out of 50 on usual care (risk ratio 0.46, 95% CI 0.26 to 0.81). The frequency of COPD exacerbations per person in a year was also lower in the PPI plus usual care group than in the usual care alone group（0.34 ± 0.72 vs 1.18 ± 1.40; P < 0.001). The number of people with at least one cold over the year was similar in both groups: 26 people on lansoprazole and 27 people in the usual care group. We judged the evidence to be of low to very low certainty, according to GRADE criteria. The study reported no data on pneumonia and other serious adverse events, quality of life, lung function test indices or disease-specific adverse events. The risk of bias was largely low or unclear for the majority of domains, though the performance bias was a high risk, as the study was not blinded. AUTHORS' CONCLUSIONS: Evidence identified by this review is insufficient to determine whether treatment with PPIs is a potential option for COPD. The sample size of the included trial is small, and the evidence is low to very low-certainty. The efficacy and safety profile of PPIs for people with COPD remains uncertain. Future large-scale, high-quality studies are warranted, which investigate major clinical outcomes such as COPD exacerbation rate, serious adverse events and quality of life.

Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.

BACKGROUND: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder. METHODS: We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291. FINDINGS: We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89-2·41) for amitriptyline and 1·37 (1·16-1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72-0·97) and fluoxetine (0·88, 0·80-0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01-1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43-0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30-2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low. INTERPRETATION: All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants. FUNDING: National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.

Amok: a mirror of time and people. A historical review of literature.

The conceptualization of psychiatric disorders changes continuously. This study examined 'amok', a culture-bound syndrome related to sudden mass homicide, to elucidate changing and varied concepts. A historical review of 88 English articles revealed that the meanings and assumed causes of amok have changed over time. These changes appear to have been affected by social events, medical discoveries, knowledge of descriptors and occasionally, the benefit to users. In other words, the concept of amok changes depending on the history of society and the knowledge and intention of people at the time. We should consider in detail what we focus on when diagnosing a disorder.

Dismantling cognitive-behaviour therapy for panic disorder: a systematic review and component network meta-analysis.

Cognitive-behaviour therapy (CBT) for panic disorder may consist of different combinations of several therapeutic components such as relaxation, breathing retraining, cognitive restructuring, interoceptive exposure and/or in vivo exposure. It is therefore important both theoretically and clinically to examine whether specific components of CBT or their combinations are superior to others in the treatment of panic disorder. Component network meta-analysis (NMA) is an extension of standard NMA that can be used to disentangle the treatment effects of different components included in composite interventions. We searched MEDLINE, EMBASE, PsycINFO and Cochrane Central, with supplementary searches of reference lists and clinical trial registries, for all randomized controlled trials comparing different CBT-based psychological therapies for panic disorder with each other or with control interventions. We applied component NMA to disentangle the treatment effects of different components included in these interventions. After reviewing 2526 references, we included 72 studies with 4064 participants. Interoceptive exposure and face-to-face setting were associated with better treatment efficacy and acceptability. Muscle relaxation and virtual-reality exposure were associated with significantly lower efficacy. Components such as breathing retraining and in vivo exposure appeared to improve treatment acceptability while having small effects on efficacy. The comparison of the most v. the least efficacious combination, both of which may be provided as 'evidence-based CBT,' yielded an odds ratio for the remission of 7.69 (95% credible interval: 1.75 to 33.33). Effective CBT packages for panic disorder would include face-to-face and interoceptive exposure components, while excluding muscle relaxation and virtual-reality exposure.

Correction: Smartphone Cognitive Behavioral Therapy as an Adjunct to Pharmacotherapy for Refractory Depression: Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/jmir.8602.].

Smartphone Cognitive Behavioral Therapy as an Adjunct to Pharmacotherapy for Refractory Depression: Randomized Controlled Trial.

BACKGROUND: In the treatment of major depression, antidepressants are effective but not curative. Cognitive behavioral therapy (CBT) is also effective, alone or in combination with pharmacotherapy, but accessibility is a problem. OBJECTIVE: The aim is to evaluate the effectiveness of a smartphone CBT app as adjunctive therapy among patients with antidepressant-resistant major depression. METHODS: A multisite, assessor-masked, parallel-group randomized controlled trial was conducted in 20 psychiatric clinics and hospitals in Japan. Participants were eligible if they had a primary diagnosis of major depression and were antidepressant-refractory after taking one or more antidepressants at an adequate dosage for four or more weeks. After a 1-week run-in in which participants started the medication switch and had access to the welcome session of the app, patients were randomized to medication switch alone or to medication switch plus smartphone CBT app via the centralized Web system. The smartphone app, called Kokoro-app ("kokoro" means "mind" in Japanese), included sessions on self-monitoring, behavioral activation, and cognitive restructuring presented by cartoon characters. The primary outcome was depression severity as assessed by masked telephone assessors with the Patient Health Questionnaire-9 (PHQ-9) at week 9. The secondary outcomes included the Beck Depression Inventory-II (BDI-II) and Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER). RESULTS: In the total sample (N=164), 81 participants were allocated to the smartphone CBT in addition to medication change and 83 to medication change alone. In the former group, all but one participant (80/81, 99%) completed at least half, and 71 (88%) completed at least six of eight sessions. In the intention-to-treat analysis, patients allocated the CBT app scored 2.48 points (95% CI 1.23-3.72, P<.001; standardized mean difference 0.40) lower on PHQ-9 than the control at week 9. The former group also scored 4.1 points (95% CI 1.5-6.6, P=.002) lower on BDI-II and 0.76 points (95% CI -0.05 to 1.58, P=.07) lower on FIBSER. In the per-protocol sample (comfortable with the smartphone app, still symptomatic, and adherent to medication with mild or less side effects after run-in), the intervention group (n=60) scored 1.72 points (95% CI 0.25-3.18, P=.02) lower on PHQ-9, 3.2 points (95% CI -0.01 to 6.3, P=.05) lower on BDI-II, and 0.75 points (95% CI 0.03-1.47, P=.04) lower on FIBSER than the control (n=57). The treatment benefits were maintained up to week 17. CONCLUSIONS: This is the first study to demonstrate the effectiveness of a smartphone CBT in the treatment of clinically diagnosed depression. Given the merits of the mobile mental health intervention, including accessibility, affordability, quality control, and effectiveness, it is clinically worthwhile to consider adjunctive use of a smartphone CBT app when treating patients with antidepressant-resistant depression. Research into its effectiveness in wider clinical contexts is warranted. TRIAL REGISTRATION: Japanese Clinical Trials Registry UMIN CTR 000013693; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000015984 (Archived by WebCite at http://www.webcitation.org/6u6pxVwik).

Choto-san versus placebo for patients with dementia: systematic review and meta-analysis.

BACKGROUND: Choto-san is a traditional medicine used for hypertension and headaches in Japan and China. Some studies have shown its effectiveness in the treatment of dementia. The present review aimed to assess the effectiveness and acceptability of Choto-san in the treatment of adults with cognitive impairment. METHODS: We included randomized controlled trials comparing Choto-san with placebo for patients with dementia or mild cognitive impairment. RESULTS: Three randomized controlled trials evaluating 219 participants were included. Two were studies on vascular dementia, and the other was on Alzheimer's dementia. There was no difference between Choto-san and placebo in terms of short-term dichotomous judgement of improvement, but Choto-san was more effective than placebo in terms of short-term improvement of cognitive function as measured by continuous outcomes. Also, dropouts judged it to be acceptable. However, the results were imprecise and/or heterogeneous. The number of participants included in the analysis was small (n = 199 in the primary analysis) and sometimes inconsistent, as indicated by the large I 2 (72% in the primary analysis). CONCLUSION: Low-quality evidence was suggestive of Choto-san's efficacy for vascular dementia, but the present results may be overestimated. Studies with a larger sample size and conducted over longer periods should be performed. Regardless, Choto-san can be one of the choices for the treatment of vascular dementia as it is well tolerated.

Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis.

BACKGROUND: Panic disorder is characterised by the presence of recurrent unexpected panic attacks, discrete periods of fear or anxiety that have a rapid onset and include symptoms such as racing heart, chest pain, sweating and shaking. Panic disorder is common in the general population, with a lifetime prevalence of 1% to 4%. A previous Cochrane meta-analysis suggested that psychological therapy (either alone or combined with pharmacotherapy) can be chosen as a first-line treatment for panic disorder with or without agoraphobia. However, it is not yet clear whether certain psychological therapies can be considered superior to others. In order to answer this question, in this review we performed a network meta-analysis (NMA), in which we compared eight different forms of psychological therapy and three forms of a control condition. OBJECTIVES: To assess the comparative efficacy and acceptability of different psychological therapies and different control conditions for panic disorder, with or without agoraphobia, in adults. SEARCH METHODS: We conducted the main searches in the CCDANCTR electronic databases (studies and references registers), all years to 16 March 2015. We conducted complementary searches in PubMed and trials registries. Supplementary searches included reference lists of included studies, citation indexes, personal communication to the authors of all included studies and grey literature searches in OpenSIGLE. We applied no restrictions on date, language or publication status. SELECTION CRITERIA: We included all relevant randomised controlled trials (RCTs) focusing on adults with a formal diagnosis of panic disorder with or without agoraphobia. We considered the following psychological therapies: psychoeducation (PE), supportive psychotherapy (SP), physiological therapies (PT), behaviour therapy (BT), cognitive therapy (CT), cognitive behaviour therapy (CBT), third-wave CBT (3W) and psychodynamic therapies (PD). We included both individual and group formats. Therapies had to be administered face-to-face. The comparator interventions considered for this review were: no treatment (NT), wait list (WL) and attention/psychological placebo (APP). For this review we considered four short-term (ST) outcomes (ST-remission, ST-response, ST-dropouts, ST-improvement on a continuous scale) and one long-term (LT) outcome (LT-remission/response). DATA COLLECTION AND ANALYSIS: As a first step, we conducted a systematic search of all relevant papers according to the inclusion criteria. For each outcome, we then constructed a treatment network in order to clarify the extent to which each type of therapy and each comparison had been investigated in the available literature. Then, for each available comparison, we conducted a random-effects meta-analysis. Subsequently, we performed a network meta-analysis in order to synthesise the available direct evidence with indirect evidence, and to obtain an overall effect size estimate for each possible pair of therapies in the network. Finally, we calculated a probabilistic ranking of the different psychological therapies and control conditions for each outcome. MAIN RESULTS: We identified 1432 references; after screening, we included 60 studies in the final qualitative analyses. Among these, 54 (including 3021 patients) were also included in the quantitative analyses. With respect to the analyses for the first of our primary outcomes, (short-term remission), the most studied of the included psychological therapies was CBT (32 studies), followed by BT (12 studies), PT (10 studies), CT (three studies), SP (three studies) and PD (two studies).The quality of the evidence for the entire network was found to be low for all outcomes. The quality of the evidence for CBT vs NT, CBT vs SP and CBT vs PD was low to very low, depending on the outcome. The majority of the included studies were at unclear risk of bias with regard to the randomisation process. We found almost half of the included studies to be at high risk of attrition bias and detection bias. We also found selective outcome reporting bias to be present and we strongly suspected publication bias. Finally, we found almost half of the included studies to be at high risk of researcher allegiance bias.Overall the networks appeared to be well connected, but were generally underpowered to detect any important disagreement between direct and indirect evidence. The results showed the superiority of psychological therapies over the WL condition, although this finding was amplified by evident small study effects (SSE). The NMAs for ST-remission, ST-response and ST-improvement on a continuous scale showed well-replicated evidence in favour of CBT, as well as some sparse but relevant evidence in favour of PD and SP, over other therapies. In terms of ST-dropouts, PD and 3W showed better tolerability over other psychological therapies in the short term. In the long term, CBT and PD showed the highest level of remission/response, suggesting that the effects of these two treatments may be more stable with respect to other psychological therapies. However, all the mentioned differences among active treatments must be interpreted while taking into account that in most cases the effect sizes were small and/or results were imprecise. AUTHORS' CONCLUSIONS: There is no high-quality, unequivocal evidence to support one psychological therapy over the others for the treatment of panic disorder with or without agoraphobia in adults. However, the results show that CBT - the most extensively studied among the included psychological therapies - was often superior to other therapies, although the effect size was small and the level of precision was often insufficient or clinically irrelevant. In the only two studies available that explored PD, this treatment showed promising results, although further research is needed in order to better explore the relative efficacy of PD with respect to CBT. Furthermore, PD appeared to be the best tolerated (in terms of ST-dropouts) among psychological treatments. Unexpectedly, we found some evidence in support of the possible viability of non-specific supportive psychotherapy for the treatment of panic disorder; however, the results concerning SP should be interpreted cautiously because of the sparsity of evidence regarding this treatment and, as in the case of PD, further research is needed to explore this issue. Behaviour therapy did not appear to be a valid alternative to CBT as a first-line treatment for patients with panic disorder with or without agoraphobia.

Psychological therapies versus pharmacological interventions for panic disorder with or without agoraphobia in adults.

BACKGROUND: Panic disorder is common and deleterious to mental well-being. Psychological therapies and pharmacological interventions are both used as treatments for panic disorder with and without agoraphobia. However, there are no up-to-date reviews on the comparative efficacy and acceptability of the two treatment modalities, and such a review is necessary for improved treatment planning for this disorder. OBJECTIVES: To assess the efficacy and acceptability of psychological therapies versus pharmacological interventions for panic disorder, with or without agoraphobia, in adults. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Group Specialised Register on 11 September 2015. This register contains reports of relevant randomised controlled trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950 to present), Embase (1974 to present), and PsycINFO (1967 to present). We cross-checked reference lists of relevant papers and systematic reviews. We did not apply any restrictions on date, language, or publication status. SELECTION CRITERIA: We included all randomised controlled trials comparing psychological therapies with pharmacological interventions for panic disorder with or without agoraphobia as diagnosed by operationalised criteria in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and resolved any disagreements in consultation with a third review author. For dichotomous data, we calculated risk ratios (RR) with 95% confidence intervals (CI). We analysed continuous data using standardised mean differences (with 95% CI). We used the random-effects model throughout. MAIN RESULTS: We included 16 studies with a total of 966 participants in the present review. Eight of the studies were conducted in Europe, four in the USA, two in the Middle East, and one in Southeast Asia.None of the studies reported long-term remission/response (long term being six months or longer from treatment commencement).There was no evidence of a difference between psychological therapies and selective serotonin reuptake inhibitors (SSRIs) in terms of short-term remission (RR 0.85, 95% CI 0.62 to 1.17; 6 studies; 334 participants) or short-term response (RR 0.97, 95% CI 0.51 to 1.86; 5 studies; 277 participants) (very low-quality evidence), and no evidence of a difference between psychological therapies and SSRIs in treatment acceptability as measured using dropouts for any reason (RR 1.33, 95% CI 0.80 to 2.22; 6 studies; 334 participants; low-quality evidence).There was no evidence of a difference between psychological therapies and tricyclic antidepressants in terms of short-term remission (RR 0.82, 95% CI 0.62 to 1.09; 3 studies; 229 participants), short-term response (RR 0.75, 95% CI 0.51 to 1.10; 4 studies; 270 participants), or dropouts for any reason (RR 0.83, 95% CI 0.53 to 1.30; 5 studies; 430 participants) (low-quality evidence).There was no evidence of a difference between psychological therapies and other antidepressants in terms of short-term remission (RR 0.90, 95% CI 0.48 to 1.67; 3 studies; 135 participants; very low-quality evidence) and evidence that psychological therapies did not significantly increase or decrease the short-term response over other antidepressants (RR 0.96, 95% CI 0.67 to 1.37; 3 studies; 128 participants) or dropouts for any reason (RR 1.55, 95% CI 0.91 to 2.65; 3 studies; 180 participants) (low-quality evidence).There was no evidence of a difference between psychological therapies and benzodiazepines in terms of short-term remission (RR 1.08, 95% CI 0.70 to 1.65; 3 studies; 95 participants), short-term response (RR 1.58, 95% CI 0.70 to 3.58; 2 studies; 69 participants), or dropouts for any reason (RR 1.12, 95% CI 0.54 to 2.36; 3 studies; 116 participants) (very low-quality evidence).There was no evidence of a difference between psychological therapies and either antidepressant alone or antidepressants plus benzodiazepines in terms of short-term remission (RR 0.86, 95% CI 0.71 to 1.05; 11 studies; 663 participants) and short-term response (RR 0.95, 95% CI 0.76 to 1.18; 12 studies; 800 participants) (low-quality evidence), and there was no evidence of a difference between psychological therapies and either antidepressants alone or antidepressants plus benzodiazepines in terms of treatment acceptability as measured by dropouts for any reason (RR 1.08, 95% CI 0.77 to 1.51; 13 studies; 909 participants; very low-quality evidence). The risk of selection bias and reporting bias was largely unclear. Preplanned subgroup and sensitivity analyses limited to trials with longer-term, quality-controlled, or individual psychological therapies suggested that antidepressants might be more effective than psychological therapies for some outcomes.There were no data to contribute to a comparison between psychological therapies and serotonin-norepinephrine reuptake inhibitors (SNRIs) and subsequent adverse effects. AUTHORS' CONCLUSIONS: The evidence in this review was often imprecise. The superiority of either therapy over the other is uncertain due to the low and very low quality of the evidence with regard to short-term efficacy and treatment acceptability, and no data were available regarding adverse effects.The sensitivity analysis and investigation of the sources of heterogeneity indicated three possible influential factors: quality control of psychological therapies, the length of intervention, and the individual modality of psychological therapies.Future studies should examine the long-term effects after intervention or treatment continuation and should provide information on risk of bias, especially with regard to selection and reporting biases.

Social cohesion and health in old age: a study in southern Taiwan.

BACKGROUND: Previous studies have found that social cohesion and trust (SCT) were associated with psychological well-being and physical health. In this study, we investigated the associations between SCT and mental and physical health among community-dwelling elderly in a town in southern Taiwan. METHODS: The study population consisted of 149 community-dwelling elderly aged 65 years and older (68 men, 81 women; mean age, 75.4 ± 6.1 years) residing in the town of Dashe in southern Taiwan. Activities of daily living (ADL), SCT, depression, subjective quality of life (QOL), current medical status, past medical history, and health behaviors were assessed in face-to-face interviews. Objective neurobehavioral functions were assessed using the timed up & go (TUG) test, functional reach test, and handgrip test. RESULTS: Scores for ADL and Geriatric Depression Scale (GDS) were significantly correlated with SCT, and SCT was significantly correlated with all subjective QOL items. In addition, a strong correlation was observed between SCT and relationship with friends. Values for SCT (median ≥ 20) were significantly associated with both subjective sense of health (median ≥ 68) and subjective happiness (median ≥ 73) after adjusting for age, sex, and ADL. CONCLUSION: SCT is an important variable that influences self-rated health and happiness, independently of ADL, age, and sex. When assessing geriatric psychological function, SCT should be examined more carefully, given its association with subjective sense of health and happiness, depression, and physical function.