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.

Effectiveness of Self-Help Plus in Preventing Mental Disorders in Refugees and Asylum Seekers in Western Europe: A Multinational Randomized Controlled Trial.

INTRODUCTION: Self-Help Plus (SH+) is a group-based psychological intervention developed by the World Health Organization for managing stress. OBJECTIVE: To assess the effectiveness of SH+ in preventing mental disorders in refugees and asylum seekers in Western Europe. METHODS: We conducted a randomized controlled trial in 5 European countries. Refugees and asylum seekers with psychological distress (General Health Questionnaire score ≥3), but without a Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) or ICD/10 diagnosis of mental disorder, as assessed with the Mini International Neuropsychiatric Interview (MINI), were randomized to SH+ or enhanced treatment as usual (ETAU). The primary outcome was the frequency of mental disorders with the MINI at 6 months. Secondary outcomes included the frequency of mental disorders at postintervention, self-identified problems, psychological symptoms, and other outcomes. RESULTS: Four hundred fifty-nine individuals were randomly assigned to SH+ or ETAU. For the primary outcome, we found no difference in the frequency of mental disorders at 6 months (Cramer V = 0.007, p = 0.90, RR = 0.96; 95% CI 0.52-1.78), while the difference significantly favored SH+ at after the intervention (secondary outcome, measured within 2 weeks from the last session; Cramer V = 0.13, p = 0.01, RR = 0.50; 95% CI 0.29-0.87). CONCLUSIONS: This is the first randomized indicated prevention study with the aim of preventing the onset of mental disorders in asylum seekers and refugees in Western Europe. As a prevention effect of SH+ was not observed at 6 months, but rather after the intervention only, modalities to maintain its beneficial effect in the long term need to be identified.

Antidepressant treatment effects and country income: meta-regression analysis of individual participant data from duloxetine trials.

OBJECTIVE: In recent decades, significant numbers of pharmaceutical trials have gradually been relocated to low- and middle-income countries. However, there is little evidence regarding the transferability of trial outcomes across countries. Analysing duloxetine randomised controlled trials (RCTs) conducted in different countries, we investigated whether per capita gross national income (GNI) and healthcare expenditure (HE) are associated with pre-post mean changes of depression severity and differences in duloxetine-placebo effect sizes. METHOD: Meta-analyses included RCTs investigating duloxetine efficacy in patients with depression. Individual participant data (IPD) from multi-centre duloxetine trials were provided by the manufacturer. Data extracted from published reports also entered analyses in case of trials conducted in only one country. A meta-regression approach was applied to analyse associations of GNI and HE with standardised pre-post mean change using raw score standardisation (SMCR) and comparative effect size, that is, the mean differences (MD) in pre-post effect size between duloxetine and placebo treatment. RESULTS: 23 trials with 8417 randomised participants entered analyses. Regression coefficients indicated a negative linear relationship of SMCR with GNI (z-standardised ß = -3.61, R2  = 14.8%, p < 0.001) and HE (ß = -4.72, R2  = 24.8%, p < 0.001) for participants treated with duloxetine. Similar associations were found for placebo treatment (GNI: ß = -3.52, R2  = 23.8%, p < 0.001; ß = -3.34, R2  = 21.0% p < 0.001). Neither GNI nor HE was associated with the MD between duloxetine and placebo pre-post differences. CONCLUSIONS: Findings challenge the idea of the universal transferability of antidepressant trial outcomes across countries. Understanding the results of antidepressant RCTs demands more sophisticated clarification of context factors involved in determining effectiveness of antidepressant medication and should be discussed with a view to socio-economic context in their countries of origin.

Benzodiazepines versus placebo for panic disorder in adults.

BACKGROUND: Panic disorder is characterised by recurrent unexpected panic attacks consisting of a wave of intense fear that reaches a peak within a few minutes. Panic disorder is a common disorder, with an estimated lifetime prevalence of 1% to 5% in the general population and a 7% to 10% prevalence in primary care settings. Its aetiology is not fully understood and is probably heterogeneous.Panic disorder is treated with psychological and pharmacological interventions, often used in combination. Although benzodiazepines are frequently used in the treatment of panic disorder, guidelines recommend antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), as first-line treatment for panic disorder, particularly due to their lower incidence of dependence and withdrawal reaction when compared to benzodiazepines. Despite these recommendations, benzodiazepines are widely used in the treatment of panic disorder, probably because of their rapid onset of action. OBJECTIVES: To assess the efficacy and acceptability of benzodiazepines versus placebo in the treatment of panic disorder with or without agoraphobia in adults. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR Studies and References), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950-), Embase (1974-), and PsycINFO (1967-) up to 29 May 2018. We handsearched reference lists of relevant papers and previous systematic reviews. We contacted experts in the field for supplemental data. SELECTION CRITERIA: All double-blind (blinding of patients and personnel) controlled trials randomising adults with panic disorder with or without agoraphobia to benzodiazepine or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently checked the eligibility of studies and extracted data using a standardised form. Data were then entered data into Review Manager 5 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details, settings, and outcome measures in terms of efficacy, acceptability, and tolerability. MAIN RESULTS: We included 24 studies in the review with a total of 4233 participants, of which 2124 were randomised to benzodiazepines and 1475 to placebo. The remaining 634 participants were randomised to other active treatments in three-arm trials. We assessed the overall methodological quality of the included studies as poor. We rated all studies as at unclear risk of bias in at least three domains. In addition, we judged 20 of the 24 included studies as having a high risk of bias in at least one domain.Two primary outcomes of efficacy and acceptability showed a possible advantage of benzodiazepines over placebo. The estimated risk ratio (RR) for a response to treatment was 1.65 (95% confidence interval (CI) 1.39 to 1.96) in favour of benzodiazepines, which corresponds to an estimated number needed to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 7). The dropout rate was lower among participants treated with benzodiazepines (RR 0.50, 95% CI 0.39 to 0.64); the estimated NNTB was 6 (95% CI 5 to 9). We rated the quality of the evidence as low for both primary outcomes. The possible advantage of benzodiazepine was also seen for remission (RR 1.61, 95% CI 1.38 to 1.88) and the endpoint data for social functioning (standardised mean difference (SMD) -0.53, 95% CI -0.65 to -0.42), both with low-quality evidence. We assessed the evidence for the other secondary outcomes as of very low quality. With the exception of the analyses of the change score data for depression (SMD -0.22, 95% CI -0.48 to 0.04) and social functioning (SMD -0.32, 95% CI -0.88 to 0.24), all secondary outcome analyses showed an effect in favour of benzodiazepines compared to placebo. However, the number of dropouts due to adverse effects was higher with benzodiazepines than with placebo (RR 1.58, 95% CI 1.16 to 2.15; low-quality evidence). Furthermore, our analyses of adverse events showed that a higher proportion of participants experienced at least one adverse effect when treated with benzodiazepines (RR 1.18, 95% CI 1.02 to 1.37; low-quality evidence). AUTHORS' CONCLUSIONS: Low-quality evidence shows a possible superiority of benzodiazepine over placebo in the short-term treatment of panic disorders. The validity of the included studies is questionable due to possible unmasking of allocated treatments, high dropout rates, and probable publication bias. Moreover, the included studies were only short-term studies and did not examine the long-term efficacy nor the risks of dependency and withdrawal symptoms. Due to these limitations, our results regarding the efficacy of benzodiazepines versus placebo provide only limited guidance for clinical practice. Furthermore, the clinician's choice is not between benzodiazepines and placebo, but between benzodiazepines and other agents, notably SSRIs, both in terms of efficacy and adverse effects. The choice of treatment should therefore be guided by the patient's preference and should balance benefits and harms from treatment in a long-term perspective.

Antidepressants versus placebo for panic disorder in adults.

BACKGROUND: Panic disorder is characterised by repeated, unexpected panic attacks, which represent a discrete period of fear or anxiety that has a rapid onset, reaches a peak within 10 minutes, and in which at least four of 13 characteristic symptoms are experienced, including racing heart, chest pain, sweating, shaking, dizziness, flushing, stomach churning, faintness and breathlessness. It is common in the general population with a lifetime prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions. Amongst pharmacological agents, the National Institute for Health and Care Excellence (NICE) and the British Association for Psychopharmacology consider antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), as the first-line treatment for panic disorder, due to their more favourable adverse effect profile over monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). Several classes of antidepressants have been studied and compared, but it is still unclear which antidepressants have a more or less favourable profile in terms of effectiveness and acceptability in the treatment of this condition. OBJECTIVES: To assess the effects of antidepressants for panic disorder in adults, specifically:1. to determine the efficacy of antidepressants in alleviating symptoms of panic disorder, with or without agoraphobia, in comparison to placebo;2. to review the acceptability of antidepressants in panic disorder, with or without agoraphobia, in comparison with placebo; and3. to investigate the adverse effects of antidepressants in panic disorder, with or without agoraphobia, including the general prevalence of adverse effects, compared to placebo. SEARCH METHODS: We searched the Cochrane Common Mental Disorders' (CCMD) Specialised Register, and CENTRAL, MEDLINE, EMBASE and PsycINFO up to May 2017. We handsearched reference lists of relevant papers and previous systematic reviews. SELECTION CRITERIA: All double-blind, randomised, controlled trials (RCTs) allocating adults with panic disorder to antidepressants or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently checked eligibility and extracted data using a standard form. We entered data into Review Manager 5 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details and settings. Primary outcomes included failure to respond, measured by a range of response scales, and treatment acceptability, measured by total number of dropouts for any reason. Secondary outcomes included failure to remit, panic symptom scales, frequency of panic attacks, agoraphobia, general anxiety, depression, social functioning, quality of life and patient satisfaction, measured by various scales as defined in individual studies. We used GRADE to assess the quality of the evidence for each outcome MAIN RESULTS: Forty-one unique RCTs including 9377 participants overall, of whom we included 8252 in the 49 placebo-controlled arms of interest (antidepressant as monotherapy and placebo alone) in this review. The majority of studies were of moderate to low quality due to inconsistency, imprecision and unclear risk of selection and performance bias.We found low-quality evidence that revealed a benefit for antidepressants as a group in comparison with placebo in terms of efficacy measured as failure to respond (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.66 to 0.79; participants = 6500; studies = 30). The magnitude of effect corresponds to a number needed to treat for an additional beneficial outcome (NNTB) of 7 (95% CI 6 to 9): that means seven people would need to be treated with antidepressants in order for one to benefit. We observed the same finding when classes of antidepressants were compared with placebo.Moderate-quality evidence suggested a benefit for antidepressants compared to placebo when looking at number of dropouts due to any cause (RR 0.88, 95% CI 0.81 to 0.97; participants = 7850; studies = 30). The magnitude of effect corresponds to a NNTB of 27 (95% CI 17 to 105); treating 27 people will result in one person fewer dropping out. Considering antidepressant classes, TCAs showed a benefit over placebo, while for SSRIs and serotonin-norepinephrine reuptake inhibitor (SNRIs) we observed no difference.When looking at dropouts due to adverse effects, which can be considered as a measure of tolerability, we found moderate-quality evidence showing that antidepressants as a whole are less well tolerated than placebo. In particular, TCAs and SSRIs produced more dropouts due to adverse effects in comparison with placebo, while the confidence interval for SNRI, noradrenergic reuptake inhibitors (NRI) and other antidepressants were wide and included the possibility of no difference. AUTHORS' CONCLUSIONS: The identified studies comprehensively address the objectives of the present review.Based on these results, antidepressants may be more effective than placebo in treating panic disorder. Efficacy can be quantified as a NNTB of 7, implying that seven people need to be treated with antidepressants in order for one to benefit. Antidepressants may also have benefit in comparison with placebo in terms of number of dropouts, but a less favourable profile in terms of dropout due to adverse effects. However, the tolerability profile varied between different classes of antidepressants.The choice of whether antidepressants should be prescribed in clinical practice cannot be made on the basis of this review.Limitations in results include funding of some studies by pharmaceutical companies, and only assessing short-term outcomes.Data from the present review will be included in a network meta-analysis of psychopharmacological treatment in panic disorder, which will hopefully provide further useful information on this issue.

The evidence-practice gap in specialist mental healthcare: systematic review and meta-analysis of guideline implementation studies.

BACKGROUND: Clinical practice guidelines are not easily implemented, leading to a gap between research synthesis and their use in routine care. AIMS: To summarise the evidence relating to the impact of guideline implementation on provider performance and patient outcomes in mental healthcare settings, and to explore the performance of different strategies for guideline implementation. METHOD: A systematic review of randomised controlled trials, controlled clinical trials and before-and-after studies comparing guideline implementation strategies v. usual care, and different guideline implementation strategies, in patients with severe mental illness. RESULTS: In total, 19 studies met our inclusion criteria. The studies did not show a consistent positive effect of guideline implementation on provider performance, but a more consistent small to modest positive effect on patient outcomes. CONCLUSIONS: Guideline implementation does not seem to have an impact on provider performance, nonetheless it may influence patient outcomes positively.

Vortioxetine for depression in adults.

BACKGROUND: Major depressive disorder is a common mental disorder affecting a person's mind, behaviour and body. It is expressed as a variety of symptoms and is associated with substantial impairment. Despite a range of pharmacological and non-pharmacological treatment options, there is still room for improvement of the pharmacological treatment of depression in terms of efficacy and tolerability. The latest available antidepressant is vortioxetine. It is assumed that vortioxetine's antidepressant action is related to a direct modulation of serotonergic receptor activity and inhibition of the serotonin transporter. The mechanism of action is not fully understood, but it is claimed to be novel. Vortioxetine was placed in the category of "Other" antidepressants and may therefore provide an alternative to existing antidepressant drugs. OBJECTIVES: To assess the efficacy and acceptability of vortioxetine compared with placebo and other antidepressant drugs in the treatment of acute depression in adults. SEARCH METHODS: We searched Cochrane's Depression, Anxiety and Neurosis Review Group's Specialised Register to May 2016 without applying any restrictions to date, language or publication status. We checked reference lists of relevant studies and reviews, regulatory agency reports and trial databases. SELECTION CRITERIA: We included randomised controlled trials comparing the efficacy, tolerability, or both of vortioxetine versus placebo or any other antidepressant agent in the treatment of acute depression in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies and extracted data. We extracted data on study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. We analysed intention-to-treat (ITT) data only and used risk ratios (RR) as effect sizes for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI). Meta-analyses used random-effects models. MAIN RESULTS: We included 15 studies (7746 participants) in this review. Seven studies were placebo controlled; eight studies compared vortioxetine to serotonin-norepinephrine reuptake inhibitors (SNRIs). We were unable to identify any study that compared vortioxetine to antidepressant drugs from other classes, such as selective serotonin reuptake inhibitors (SSRIs).Vortioxetine may be more effective than placebo across the three efficacy outcomes: response (Mantel-Haenszel RR 1.35, 95% CI 1.22 to 1.49; 14 studies, 6220 participants), remission (RR 1.32, 95% CI 1.15 to 1.53; 14 studies, 6220 participants) and depressive symptoms measured using the Montgomery-Åsberg Depression Scale (MADRS) (score range: 0 to 34; higher score means worse outcome: MD -2.94, 95% CI -4.07 to -1.80; 14 studies, 5566 participants). The quality of the evidence was low for response and remission and very low for depressive symptoms. We found no evidence of a difference in total dropout rates (RR 1.05, 95% CI 0.93 to 1.19; 14 studies, 6220 participants). More participants discontinued vortioxetine than placebo because of adverse effects (RR 1.41, 95% CI 1.09 to 1.81; 14 studies, 6220 participants) but fewer discontinued due to inefficacy (RR 0.56, 95% CI 0.34 to 0.90, P = 0.02; 14 studies, 6220 participants). The quality of the evidence for dropouts was moderate.The subgroup and sensitivity analyses did not reveal factors that significantly influenced the results.In comparison with other antidepressants, very low-quality evidence from eight studies showed no clinically significant difference between vortioxetine and SNRIs as a class for response (RR 0.91, 95% CI 0.82 to 1.00; 3159 participants) or remission (RR 0.89, 95% CI 0.77 to 1.03; 3155 participants). There was a small difference favouring SNRIs for depressive symptom scores on the MADRS (MD 1.52, 95% CI 0.50 to 2.53; 8 studies, 2807 participants). Very low quality evidence from eight studies (3159 participants) showed no significant differences between vortioxetine and the SNRIs as a class for total dropout rates (RR 0.89, 95% CI 0.73 to 1.08), dropouts due to adverse events (RR 0.74, 95% CI 0.51 to 1.08) and dropouts due to inefficacy (RR 1.52, 95% CI 0.70 to 3.30).Against individual antidepressants, analyses suggested that vortioxetine may be less effective than duloxetine in terms of response rates (RR 0.86, 95% CI 0.79 to 0.94; 6 studies, 2392 participants) and depressive symptoms scores on the MADRS scale (MD 1.99, 95% CI 1.15 to 2.83; 6 studies; 2106 participants). Against venlafaxine, meta-analysis of two studies found no statistically significant differences (response: RR 1.03, 95% CI 0.85 to 1.25; 767 participants; depressive symptom scores: MD 0.02, 95% CI -2.49 to 2.54; 701 participants). In terms of number of participants reporting at least one adverse effect (tolerability), vortioxetine was better than the SNRIs as a class (RR 0.90, 95% CI 0.86 to 0.94; 8 studies, 3134 participants) and duloxetine (RR 0.89, 95% CI 0.84 to 0.95; 6 studies; 2376 participants). However, the sensitivity analysis casts some doubts on this result, as only two studies used comparable dosing.We judged none of the studies to have a high risk of bias for any domain, but we rated all studies to have an unclear risk of bias of selective reporting and other biases. AUTHORS' CONCLUSIONS: The place of vortioxetine in the treatment of acute depression is unclear. Our analyses showed vortioxetine may be more effective than placebo in terms of response, remission and depressive symptoms, but the clinical relevance of these effects is uncertain. Furthermore, the quality of evidence to support these findings was generally low. In comparison to SNRIs, we found no advantage for vortioxetine. Vortioxetine was less effective than duloxetine, but fewer people reported adverse effects when treated with vortioxetine compared to duloxetine. However, these findings are uncertain and not well supported by evidence. A major limitation of the current evidence is the lack of comparisons with the SSRIs, which are usually recommended as first-line treatments for acute depression. Studies with direct comparisons to SSRIs are needed to address this gap and may be supplemented by network meta-analyses to define the role of vortioxetine in the treatment of depression.

Men's Views on Depression: A Systematic Review and Metasynthesis of Qualitative Research.

BACKGROUND: According to the concept of "male depression," depression among men might be underdiagnosed and undertreated because of gender differences in symptoms and coping. There is evidence that men experience atypical depressive symptoms including irritability, aggression, substance abuse, and increased risk behavior. To date, a substantial number of qualitative studies on men's views on depression has been conducted in the last few decades. METHODS: Based on a systematic review and metasynthesis of qualitative studies on men's subjective perspectives on depression, we aim at a comprehensive understanding of men's subjective views on depression with a specific focus on masculinity constructions. RESULTS: Based on 34 studies assessed as appropriate for the study, 2 overarching subthemes could be identified: normative expectations regarding masculinity ideals and men's subjective perspectives of depression as "weakness." Men's strategies include denial of "weakness" and "closing up." Further themes include suicide, masculinity ideals as a healthy resource, and alternative masculinities. DISCUSSION/CONCLUSIONS: Traditional masculinity values might serve as barriers but also as facilitators to adaptive coping strategies in depressed men. More research is needed to study the dimensions and role of alternative masculinities in the context of depression.

Implementation of treatment guidelines for specialist mental health care.

BACKGROUND: A huge gap exists between the production of evidence and its uptake in clinical practice settings. To fill this gap, treatment guidelines, based on explicit assessments of the evidence base, are commonly used in several fields of psychiatry, including schizophrenia and related psychotic disorders. However, it remains unclear whether treatment guidelines have any material impact on provider performance and patient outcomes, and how implementation should be conducted to maximise benefit. OBJECTIVES: The primary objective of this review was to examine the efficacy of guideline implementation strategies in improving process outcomes (performance of healthcare providers) and patient outcomes. We also explored which components of different guideline implementation strategies could influence them. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Register (March 2012 and August 2015), as well as references of included studies. SELECTION CRITERIA: Studies that examined schizophrenia-spectrum disorders to compare guideline implementation strategies with usual care or to assess the comparative efficacy of different guideline implementation strategies. DATA COLLECTION AND ANALYSIS: Review authors worked independently and in duplicate to critically appraise records from 990 studies; six individual studies met the inclusion criteria. Among the six included studies, significant heterogeneity was found in the focus of the guideline, target of the intervention, implementation strategy, and outcome measures, so meta-analysis was carried out for antipsychotic co-prescribing only. MAIN RESULTS: This review now includes six studies, with a total of 1727 participants. Of the six included studies, practitioner impact was assessed in four. Overall, risk of bias was rated as low or unclear, and all evidence in the 'Summary of findings' tables was graded as low or very low quality. Meta-analysis revealed that a combination of several guideline dissemination and implementation strategies targeting healthcare professionals did not reduce antipsychotic co-prescribing in schizophrenia outpatients (2 RCTs, N = 1082, RR 1.10 CI 0.99 to 1.23; corrected for cluster design: N = 310, RR 0.97, CI 0.75 to 1.25, very low-quality evidence). One trial, which studied a nurse-led intervention aimed at promoting cardiovascular disease screening, found a significant effect in the proportion of people receiving screening (Framingham score: N = 110, RR 0.69, 95% CI 0.55 to 0.87), although in the analysis corrected for cluster design, the effect was no longer statistically significant (N = 38, RR 0.71, 95% CI 0.48 to 1.03, very low-quality evidence).One trial reported the patient outcomes of global state, satisfaction with care, treatment adherence, and drug attitude; no effect between treatments was seen. Quality of life was not reported by any of the studies.One trial, which studied the use of re-written guideline text compared to original text, did not find a significant effect on staff receiving training (N = 68, RR 1.03, 95% CI 0.87 to 1.21, low-quality evidence), staff receiving supervision (N = 68, RR 0.86, 95% CI 0.64 to 1.17, low-quality evidence), or staff providing psychological interventions (N = 68, RR 0.86, 95% CI 0.62 to 1.18, low-quality evidence).Regarding participant outcomes, only one trial assessed the efficacy of a shared decision-making implementation strategy and found no impact on psychopathology, satisfaction with care, or drug attitude. Another single trial studied a multifaceted intervention to promote medication adherence and found no effect on adherence rates. AUTHORS' CONCLUSIONS: Considering the available evidence, it is not possible to arrive at definitive conclusions. The preliminary pattern of evidence suggests that uncertainty remains about clinically meaningful and sustainable effects of treatment guidelines on patient outcomes and how best to implement such guidelines for maximal benefit.

Antidepressants and benzodiazepines for panic disorder in adults.

BACKGROUND: A panic attack is a discrete period of fear or anxiety that has a rapid onset, reaches a peak within 10 minutes and in which at least four of 13 characteristic symptoms are experienced, including racing heart, chest pain, sweating, shaking, dizziness, flushing, stomach churning, faintness and breathlessness. Panic disorder is common in the general population with a lifetime prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions. Amongst pharmacological agents, antidepressants and benzodiazepines are the mainstay of treatment for panic disorder. Different classes of antidepressants have been compared; and the British Association for Psychopharmacology, and National Institute for Health and Care Excellence (NICE) consider antidepressants (mainly selective serotonin reuptake inhibitors (SSRIs)) as the first-line treatment for panic disorder, due to their more favourable adverse effect profile over monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). In addition to antidepressants, benzodiazepines are widely prescribed for the treatment of panic disorder. OBJECTIVES: To assess the evidence for the effects of antidepressants and benzodiazepines for panic disorder in adults. SEARCH METHODS: The Specialised Register of the Cochrane Common Mental Disorders Group (CCMDCTR) to 11 September 2015. This register includes relevant randomised controlled trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950-), Embase (1974-) and PsycINFO (1967-). Reference lists of relevant papers and previous systematic reviews were handsearched. We contacted experts in this field for supplemental data. SELECTION CRITERIA: All double-blind randomised controlled trials allocating adult patients with panic disorder to antidepressants or benzodiazepines versus any other active treatment with antidepressants or benzodiazepines. DATA COLLECTION AND ANALYSIS: Two review authors independently checked eligibility and extracted data using a standard form. Data were entered in RevMan 5.3 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details, settings and outcome measures in terms of efficacy, acceptability and tolerability. MAIN RESULTS: Thirty-five studies, including 6785 participants overall (of which 5365 in the arms of interest (antidepressant and benzodiazepines as monotherapy)) were included in this review; however, since studies addressed many different comparisons, only a few trials provided data for primary outcomes. We found low-quality evidence suggesting no difference between antidepressants and benzodiazepines in terms of response rate (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.67 to 1.47; participants = 215; studies = 2). Very low-quality evidence suggested a benefit for benzodiazepines compared to antidepressants in terms of dropouts due to any cause, even if confidence interval (CI) ranges from almost no difference to benefit with benzodiazepines (RR 1.64, 95% CI 1.03 to 2.63; participants = 1449; studies = 7). We found some evidence suggesting that serotonin reuptake inhibitors (SSRIs) are better tolerated than TCAs (when looking at the number of patients experiencing adverse effects). We failed to find clinically significant differences between individual benzodiazepines. The majority of studies did not report details on random sequence generation and allocation concealment; similarly, no details were provided about strategies to ensure blinding. The study protocol was not available for almost all studies so it is difficult to make a judgment on the possibility of outcome reporting bias. Information on adverse effects was very limited. AUTHORS' CONCLUSIONS: The identified studies are not sufficient to comprehensively address the objectives of the present review. The majority of studies enrolled a small number of participants and did not provide data for all the outcomes specified in the protocol. For these reasons most of the analyses were underpowered and this limits the overall completeness of evidence. In general, based on the results of the current review, the possible role of antidepressants and benzodiazepines should be assessed by the clinician on an individual basis. The choice of which antidepressant and/or benzodiazepine is prescribed can not be made on the basis of this review only, and should be based on evidence of antidepressants and benzodiazepines efficacy and tolerability, including data from placebo-controlled studies, as a whole. Data on long-term tolerability issues associated with antidepressants and benzodiazepines exposure should also be carefully considered.The present review highlights the need for further higher-quality studies comparing antidepressants with benzodiazepines, which should be conducted with high-methodological standards and including pragmatic outcome measures to provide clinicians with useful and practical data. Data from the present review will be included in a network meta-analysis of psychopharmacological treatment in panic disorder, which will hopefully provide further useful information on this issue.

A systematic review of Chinese randomized clinical trials of SSRI treatment of depression.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have become the most frequently used antidepressants in China in recent decades. This systematic review and meta-analysis examined the efficacy and tolerability of SSRIs in Chinese studies and the quality of Chinese randomized controlled trials. METHODS: Major Western and Chinese electronic databases were searched for double-blind, parallel group randomised controlled trials (RCTs) comparing SSRIs (fluoxetine, citalopram, escitalopram, fluvoxamine, paroxetine, or sertraline) with other antidepressants such as SSRI, Selective Noradrenaline Reuptake Inhibitor (SNRI), tricyclic antidepressant (TCA), Traditional Chinese Medicine (TCM) and/or placebo. Response, remission, and dropout rates due to side effects were defined as primary outcomes. Mean total Hamilton Rating Scale of Depression (HAMD) scores at endpoint, overall dropout rates and total Treatment Emergent Symptom Scale (TESS) scores were defined as secondary outcomes. Data were combined with random effects models. Risk of bias was assessed by the Cochrane evaluation tool. Quality of reports was assessed by the fulfilment of Consolidated Standards of Reporting Trial (CONSORT) items. RESULTS: A total of 71 studies were included. Only one study was listed in both Chinese and Western databases. SSRIs were found to be more effective than TCAs. No significant differences were observed regarding dropout rates due to side effects. Using the Cochrane risk of bias tool, adequate methods of sequence generation were described in 16 (23%) studies. All authors failed to report trial registration. Informed consent, sources of funding, email address, protocol, and limitations were also not mentioned in most studies. However, reporting quality improved steadily between 1996 and 2013. CONCLUSIONS: In light of the low trial quality, the findings of a significant advantage of SSRI over TCA in terms of response rate and remission rate should be replicated by large high-quality Chinese studies.

Implementation of treatment guidelines for specialist mental health care.

BACKGROUND: A huge gap exists between the production of evidence and its take-up in clinical practice settings. To fill this gap, treatment guidelines, based on explicit assessments of the evidence base, are commonly employed in several fields of medicine, including schizophrenia and related psychotic disorders. It remains unclear, however, whether treatment guidelines have any impact on provider performance and patient outcomes, and how implementation should be conducted to maximise benefit. OBJECTIVES: The primary objective of this review was to examine the efficacy of guideline implementation strategies in improving process outcomes (performance of healthcare providers) and patient outcomes. We additionally explored which components of different guideline implementation strategies can influence process and patient outcomes. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Register (March 2012), as well as references of included studies. SELECTION CRITERIA: Studies that examined schizophrenia-spectrum disorders to compare guideline implementation strategies with usual care or to assess the comparative efficacy of different guideline implementation strategies. DATA COLLECTION AND ANALYSIS: Review authors worked independently and in duplicate to critically appraise records from 882 studies; five individual studies met the inclusion criteria and were considered. As critical appraisal of the five included studies revealed substantial heterogeneity in terms of focus of the guideline, target of the intervention, implementation strategy and outcome measures, meta-analysis was carried out for antipsychotic co-prescribing only. MAIN RESULTS: Of the five included studies, practitioner impact was assessed in three. The five studies were generally at unclear risk of bias, and all evidence in the 'Summary of findings' table was graded by review authors as of very low quality. Meta-analysis of two studies revealed that a combination of several guideline dissemination and implementation strategies targeting healthcare professionals did not reduce antipsychotic co-prescribing in schizophrenia outpatients (two studies, n = 1,082, risk ratio (RR) 1.10, 95% confidence interval (CI) 0.99 to 1.23; corrected for cluster design: n = 310, RR 0.97, CI 0.75 to 1.25). One trial, which studied a nurse-led intervention aimed at promoting cardiovascular disease screening, found a significant effect in terms of the proportion of people receiving screening (blood pressure: n = 96, RR 0.07, 95% CI 0.02 to 0.28; cholesterol: n = 103, RR 0.46, 95% CI 0.30 to 0.70; glucose: n = 103, RR 0.53, 95% CI 0.34 to 0.82; BMI: n = 99, RR 0.22, 95% CI 0.08 to 0.60; smoking status: n = 96, RR 0.28, 95% CI 0.12 to 0.64; Framingham score: n = 110, RR 0.69, 95% CI 0.55 to 0.87), although in the analysis corrected for cluster design, the effect was statistically significant for blood pressure and cholesterol only (blood pressure, corrected for cluster design: n = 33, RR 0.10, 95% CI 0.01 to 0.74; cholesterol, corrected for cluster design: n = 35, RR 0.49, 95% CI 0.24 to 0.99; glucose, corrected for cluster design: n = 35, RR 0.58, 95% CI 0.28 to 1.21; BMI, corrected for cluster design: n = 34, RR 0.18, 95% CI 0.02 to 1.37; smoking status, corrected for cluster design: n = 32, RR 0.25, 95% CI 0.06 to 1.03; Framingham score, corrected for cluster design: n = 38, RR 0.71, 95% CI 0.48 to 1.03; very low quality). Regarding participant outcomes, one trial assessed the efficacy of a shared decision-making implementation strategy and found no impact in terms of psychopathology, satisfaction with care and drug attitude. Another single trial studied a multifaceted intervention to promote medication adherence and found no impact in terms of adherence rates. AUTHORS' CONCLUSIONS: With only five studies meeting inclusion criteria, and with limited low or very low quality usable information, it is not possible to arrive at definitive conclusions. The preliminary pattern of evidence suggests that, although small changes in psychiatric practice have been demonstrated, uncertainty remains in terms of clinically meaningful and sustainable effects of treatment guidelines on patient outcomes and how best to implement such guidelines for maximal benefit.

Azapirones versus placebo for panic disorder in adults.

BACKGROUND: Panic disorder is common in the general population. It is often associated with other psychiatric disorders, such as drug dependence, major depression, bipolar disorder, social phobia, specific phobia and generalised anxiety disorder. Azapirones are a class of drugs used as anxiolytics. They are associated with less drowsiness, psychomotor impairment, alcohol potentiation and potential for addiction or abuse than benzodiazepines. However, azapirones are not widely used in the treatment of panic disorder and evidence for their efficacy is unclear. It is important to find out if azapirones are effective and acceptable in the treatment of panic disorder. OBJECTIVES: To assess the effects of azapirones on panic disorder in adults, specifically:1. to determine the efficacy of azapirones in alleviating symptoms of panic disorder, with or without agoraphobia, in comparison with placebo;2. to review the acceptability of azapirones in panic disorder, with or without agoraphobia, in comparison with placebo; and3. to investigate adverse effects of azapirones in panic disorder with or without agoraphobia, including general prevalence of adverse effects, compared with placebo. SEARCH METHODS: We searched the Cochrane Depression Anxiety and Neurosis Group Trials Specialised Register (CCDANCTR, search date: 10th January 2014), which includes relevant randomised controlled trials from The Cochrane Library (all years), MEDLINE (1950-), EMBASE (1974-), and PsycINFO (1967-). SELECTION CRITERIA: Randomised controlled trials that compared azapirones with placebo for panic disorder in adults. DATA COLLECTION AND ANALYSIS: Three review authors independently identified studies, assessed trial quality and extracted data. We contacted study authors for additional information. MAIN RESULTS: Three studies involving 170 participants compared the azapirone buspirone with placebo. No study provided enough usable information on our primary efficacy outcome (response). For our primary acceptability outcome, moderate-quality evidence indicated that azapirones had lower acceptability than placebo: risk ratio (RR) for dropouts for any reason 2.13 (95% confidence interval (CI) 1.11 to 4.07; 3 studies, 170 participants. Evidence for secondary efficacy outcomes were of low quality. Results on efficacy between azapirone and placebo in terms of agoraphobia (standardised mean difference (SMD) -0.01, 95% CI -0.56 to 0.53; 1 study, 52 participants), general anxiety (mean difference (MD) -2.20, 95% CI -5.45 to 1.06; 2 studies, 115 participants) and depression (MD -1.80, 95% CI -5.60 to 2.00; 1 study, 52 participants) were uncertain. None of the studies provided information for the assessment of allocation concealment or sequence generation. Conflicts of interest were not explicitly expressed. The risk of attrition bias was rated high for all three studies. Information on adverse effects other than dropouts for any reason was insufficient to include in the analyses. AUTHORS' CONCLUSIONS: The efficacy of azapirones is uncertain due to the lack of meta-analysable data for the primary outcome and low-quality evidence for secondary efficacy outcomes. A small amount of moderate-quality evidence suggested that the acceptability of azapirones for panic disorder was lower than for placebo. However, only trials of one azapirone (namely buspirone) were included in this review; this, combined with the small sample size, limits our conclusions. If further research is to be conducted, studies with larger sample sizes, with different azapirones and with less risk of bias are necessary to draw firm conclusions regarding azapirones for panic disorder.

Agomelatine efficacy and acceptability revisited: systematic review and meta-analysis of published and unpublished randomised trials.

BACKGROUND: Agomelatine is a novel antidepressant drug with narrative, non-systematic reviews making claims of efficacy. AIMS: The present study systematically reviewed published and unpublished evidence of the acute and long-term efficacy and acceptability of agomelatine compared with placebo in the treatment of major depression. METHOD: Randomised controlled trials comparing agomelatine with placebo in the treatment of unipolar major depression were systematically reviewed. Primary outcomes were (a) Hamilton Rating Scale for Depression (HRSD) score at the end of treatment (short-term studies) and (b) number of relapses (long-term studies). RESULTS: Meta-analyses included 10 acute-phase and 3 relapse prevention studies. Seven of the included studies were unpublished. Acute treatment with agomelatine was associated with a statistically significant superiority over placebo of -1.51 HRSD points (99% CI -2.29 to -0.73, nine studies). Data extracted from three relapse prevention studies failed to show significant effects of agomelatine over placebo (relative risk 0.78, 99% CI 0.41-1.48). Secondary efficacy analyses showed a significant advantage of agomelatine over placebo in terms of response (with no effect for remission). None of the negative trials were published and conflicting results between published and unpublished studies were observed. CONCLUSIONS: We found evidence suggesting that a clinically important difference between agomelatine and placebo in patients with unipolar major depression is unlikely. There was evidence of substantial publication bias.

Agomelatine versus other antidepressive agents for major depression.

BACKGROUND: Major depressive disorder (MDD), or depression, is a syndrome characterised by a number of behavioural, cognitive and emotional features. It is most commonly associated with a sad or depressed mood, a reduced capacity to feel pleasure, feelings of hopelessness, loss of energy, altered sleep patterns, weight fluctuations, difficulty in concentrating and suicidal ideation. There is a need for more effective and better tolerated antidepressants to combat this condition. Agomelatine was recently added to the list of available antidepressant drugs; it is a novel antidepressant that works on melatonergic (MT1 and MT2), 5-HT 2B and 5-HT2C receptors. Because the mechanism of action is claimed to be novel, it may provide a useful, alternative pharmacological strategy to existing antidepressant drugs. OBJECTIVES: The objective of this review was 1) to determine the efficacy of agomelatine in alleviating acute symptoms of major depressive disorder in comparison with other antidepressants, 2) to review the acceptability of agomelatine in comparison with other antidepressant drugs, and, 3) to investigate the adverse effects of agomelatine, including the general prevalence of side effects in adults. SEARCH METHODS: We searched the Cochrane Collaboration's Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to 31 July 2013. The CCDANCTR includes relevant randomised controlled trials from the following bibliographic databases: CENTRAL (the Cochrane Central Register of Controlled Trials) (all years), EMBASE (1974 onwards), MEDLINE (1950 onwards) and PsycINFO (1967 onwards). We checked reference lists of relevant studies together with reviews and regulatory agency reports. No restrictions on date, language or publication status were applied to the search. Servier Laboratories (developers of agomelatine) and other experts in the field were contacted for supplemental data. SELECTION CRITERIA: Randomised controlled trials allocating adult participants with major depression to agomelatine versus any other antidepressive agent. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and a double-entry procedure was employed. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. MAIN RESULTS: A total of 13 studies (4495 participants) were included in this review. Agomelatine was compared to selective serotonin reuptake inhibitors (SSRIs), namely paroxetine, fluoxetine, sertraline, escitalopram, and to the serotonin-norepinephrine reuptake inhibitor (SNRI), venlafaxine. Participants were followed up for six to 12 weeks. Agomelatine did not show any advantage or disadvantage over the other antidepressants for our primary outcome, response to treatment (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.95 to 1.08, P value 0.75 compared to SSRIs, and RR 1.06; 95% CI 0.98 to 1.16, P value 0.16 compared to venlafaxine). Also, agomelatine showed no advantage or disadvantage over other antidepressants for remission (RR 0.83; 95% CI 0.68 to 1.01, P value 0.07 compared to SSRIs, and RR 1.08; 95% CI 0.94 to 1.24, P value 0.73 compared to venlafaxine). Overall, agomelatine appeared to be better tolerated than venlafaxine in terms of lower rates of drop outs (RR 0.40; 95% CI 0.24 to 0.67, P value 0.0005), and showed the same level of tolerability as SSRIs (RR 0.95; 95% CI 0.83 to 1.09, P value 0.44). Agomelatine induced a lower rate of dizziness than venlafaxine (RR 0.19, 95% CI 0.06 to 0.64, P value 0.007).With regard to the quality of the body of evidence, there was a moderate risk of bias for all outcomes, due to the number of included unpublished studies. There was some heterogeneity, particularly between published and unpublished studies. The included studies were conducted in inpatient and outpatient settings, thus limiting the generalisability of the results to primary care settings. With regard to precision, the efficacy outcomes were precise, but the tolerability outcomes were mostly imprecise. Publication bias was variable and depended on the outcome of the trial. Our review included unpublished studies, and we think that this reduced the impact of publication bias. The overall methodological quality of the studies was not very good. Almost all of the studies were sponsored by the pharmaceutical company that manufactures agomelatine (Servier), and some of these were unpublished. Attempts to contact the pharmaceutical company Servier for additional information on all unpublished studies were unsuccessful. AUTHORS' CONCLUSIONS: Agomelatine did not seem to provide a significant advantage in efficacy over other antidepressive agents for the acute-phase treatment of major depression. Agomelatine was better tolerated than paroxetine and venlafaxine in terms of overall side effects, and fewer participants treated with agomelatine dropped out of the trials due to side effects compared to sertraline and venlafaxine, but data were limited because the number of included studies was small. We found evidence that compared agomelatine with only a small number of other active antidepressive agents, and there were only a few trials for each comparison, which limits the generalisability of the results. Moreover, the overall methodological quality of the studies was low, and, therefore, no firm conclusions can be drawn concerning the efficacy and tolerability of agomelatine.

Self-Help Plus for refugees and asylum seekers: an individual participant data meta-analysis.

QUESTION: Refugees and asylum seekers are at high risk of mental disorders due to various stressors before, during and after forceful displacement. The WHO Self-Help Plus (SH+) intervention was developed to manage psychological distress and a broad range of mental health symptoms in vulnerable populations. This study aimed to examine the effects and moderators of SH+ compared with Enhanced Care as Usual (ECAU) in reducing depressive symptoms among refugees and asylum seekers. STUDY SELECTION AND ANALYSIS: Three randomised trials were identified with 1795 individual participant data (IPD). We performed an IPD meta-analysis to estimate the effects of SH+, primarily on depressive symptoms and second on post-traumatic stress, well-being, self-identified problems and functioning. Effects were also estimated at 5-6 months postrandomisation (midterm). FINDINGS: There was no evidence of a difference between SH+ and ECAU+ in reducing depressive symptoms at postintervention. However, SH+ had significantly larger effects among participants who were not employed (ß=1.60, 95% CI 0.20 to 3.00) and had lower mental well-being levels (ß=0.02, 95% CI 0.001 to 0.05). At midterm, SH+ was significantly more effective than ECAU in improving depressive symptoms (ß=-1.13, 95% CI -1.99 to -0.26), self-identified problems (ß=-1.56, 95% CI -2.54 to -0.59) and well-being (ß=6.22, 95% CI 1.60 to 10.90). CONCLUSIONS: Although SH+ did not differ significantly from ECAU in reducing symptoms of depression at postintervention, it did present benefits for particularly vulnerable participants (ie, unemployed and with lower mental well-being levels), and benefits were also evident at midterm follow-up. These results are promising for the use of SH+ in the management of depressive symptoms and improvement of well-being and self-identified problems among refugees and asylum seekers.

Risk factors for mental disorder development in asylum seekers and refugees resettled in Western Europe and Turkey: Participant-level analysis of two large prevention studies.

BACKGROUND: In asylum seekers and refugees, the frequency of mental disorders, such as depression, anxiety and post-traumatic stress disorder, is higher than the general population, but there is a lack of data on risk factors for the development of mental disorders in this population. AIM: This study investigated the risk factors for mental disorder development in a large group of asylum seekers and refugees resettled in high- and middle-income settings. METHODS: Participant-level data from two randomized prevention studies involving asylum seekers and refugees resettled in Western European countries and in Turkey were pooled. The two studies randomized participants with psychological distress, but without a diagnosis of mental disorder, to the Self-Help Plus psychological intervention or enhanced care as usual. At baseline, exposure to potentially traumatic events was measured using the Harvard Trauma Questionnaire-part I, while psychological distress and depressive symptoms were assessed with the General Health Questionnaire and the Patient Health Questionnaire. After 3 and 6 months of follow-up, the proportion of participants who developed a mental disorder was calculated using the Mini International Neuropsychiatric Interview. RESULTS: A total of 1,101 participants were included in the analysis. At 3- and 6-month follow-up the observed frequency of mental disorders was 13.51% (115/851) and 24.30% (207/852), respectively, while the frequency estimates after missing data imputation were 13.95% and 23.78%, respectively. After controlling for confounders, logistic regression analysis showed that participants with a lower education level (p = .034), a shorter duration of journey (p = .057) and arriving from countries with war-related contexts (p = .017), were more at risk of developing mental disorders. Psychological distress (p = .004), depression (p = .001) and exposure to potentially traumatic events (p = .020) were predictors of mental disorder development. CONCLUSIONS: This study identified several risk factors for the development of mental disorders in asylum seekers and refugees, some of which may be the target of risk reduction policies. The identification of asylum seekers and refugees at increased risk of mental disorders should guide the implementation of focused preventative psychological interventions.

Impairments in psychological functioning in refugees and asylum seekers.

Refugees are at increased risk for developing psychological impairments due to stressors in the pre-, peri- and post-migration periods. There is limited knowledge on how everyday functioning is affected by migration experience. In a secondary analysis of a study in a sample of refugees and asylum seekers, it was examined how aspects of psychological functioning were differentially affected. 1,101 eligible refugees and asylum seekers in Europe and Türkiye were included in a cross-sectional analysis. Gender, age, education, number of relatives and children living nearby, as well as indicators for depressive and posttraumatic symptoms, quality of life, psychological well-being and functioning, and lifetime potentially traumatic events were assessed. Correlations and multiple regression models with World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) 12-item version's total and six subdomains' scores ('mobility', 'life activities', 'cognition', 'participation', 'self-care', 'getting along') as dependent variables were calculated. Tests for multicollinearity and Bonferroni correction were applied. Participants reported highest levels of impairment in 'mobility' and 'participation', followed by 'life activities' and 'cognition'. Depression and posttraumatic symptoms were independently associated with overall psychological functioning and all subdomains. History of violence and abuse seemed to predict higher impairment in 'participation', while past events of being close to death were associated with fewer issues with 'self-care'. Impairment in psychological functioning in asylum seekers and refugees was related to current psychological symptoms. Mobility and participation issues may explain difficulties arising after resettlement in integration and exchange with host communities in new contexts.

Duloxetine versus other anti-depressive agents for depression.

BACKGROUND: Although pharmacological and psychological interventions are both effective for major depression, in primary and secondary care settings antidepressant drugs remain the mainstay of treatment. Amongst antidepressants many different agents are available. Duloxetine hydrochloride is a dual reuptake inhibitor of serotonin and norepinephrine and has been licensed by the Food and Drug Administration in the US for major depressive disorder (MDD), generalised anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia and chronic musculoskeletal pain. OBJECTIVES: To assess the evidence for the efficacy, acceptability and tolerability of duloxetine in comparison with all other antidepressant agents in the acute-phase treatment of major depression. SEARCH METHODS: MEDLINE (1966 to 2012), EMBASE (1974 to 2012), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to March 2012. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical company marketing duloxetine and experts in this field were contacted for supplemental data. SELECTION CRITERIA: Randomised controlled trials allocating patients with major depression to duloxetine versus any other antidepressive agent. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and a double-entry procedure was employed. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. MAIN RESULTS: A total of 16 randomised controlled trials (overall 5735 participants) were included in this systematic review. Of these, three trials were unpublished. We found 11 studies (overall 3304 participants) comparing duloxetine with one selective serotonin reuptake inhibitor (SSRI) (six studies versus paroxetine, three studies versus escitalopram and two versus fluoxetine), four studies (overall 1978 participants) comparing duloxetine with a newer antidepressants (three with venlafaxine and one with desvenlafaxine, respectively) and one study (overall 453 participants) comparing duloxetine with an antipsychotic drug which is also used as an antidepressive agent, quetiapine. No studies were found comparing duloxetine with tricyclic antidepressants. The pooled confidence intervals were rather wide and there were no statistically significant differences in efficacy when comparing duloxetine with other antidepressants. However, when compared with escitalopram or venlafaxine, there was a higher rate of drop out due to any cause in the patients randomised to duloxetine (odds ratio (OR) 1.62; 95% confidence interval (CI) 1.01 to 2.62 and OR 1.56; 95% CI 1.14 to 2.15, respectively). There was also some weak evidence suggesting that patients taking duloxetine experienced more adverse events than paroxetine (OR 1.24; 95% CI 0.99 to 1.55). AUTHORS' CONCLUSIONS: Duloxetine did not seem to provide a significant advantage in efficacy over other antidepressive agents for the acute-phase treatment of major depression. No differences in terms of efficacy were found, even though duloxetine was worse than some SSRIs (most of all, escitalopram) and newer antidepressants (like venlafaxine) in terms of acceptability and tolerability. Unfortunately, we only found evidence comparing duloxetine with a handful of other active antidepressive agents and only a few trials per comparison were found (in some cases we retrieved just one trial). This limited the power of the review to detect moderate, but clinically meaningful differences between the drugs. As many statistical tests have been used in the review, the findings from this review are better thought of as hypothesis forming rather than hypothesis testing and it would be very comforting to see the conclusions replicated in future trials. Most of included studies were sponsored by the drug industry manufacturing duloxetine. As for all other new investigational compounds, the potential for overestimation of treatment effect due to sponsorship bias should be borne in mind. In the present review no trials reported economic outcomes. Given that several SSRIs and the great majority of antidepressants are now available as generic formulation (only escitalopram, desvenlafaxine and duloxetine are still on patent), more comprehensive economic estimates of antidepressant treatment effect should be considered to better inform healthcare policy.

Preventing the mental health consequences of war in refugee populations.

The refugee experience is associated with several potentially traumatic events that increase the risk of developing mental health consequences, including worsening of subjective wellbeing and quality of life, and risk of developing mental disorders. Here we present actions that countries hosting forcibly displaced refugees may implement to decrease exposure to potentially traumatic stressors, enhance subjective wellbeing and prevent the onset of mental disorders. A first set of actions refers to the development of reception conditions aiming to decrease exposure to post-migration stressors, and a second set of actions refers to the implementation of evidence-based psychological interventions aimed at reducing stress, preventing the development of mental disorders and enhancing subjective wellbeing.