The efficacy of app‐supported smartphone interventions for mental health problems: a meta‐analysis of randomized controlled trials

Although impressive progress has been made toward developing empirically‐supported psychological treatments, the reality remains that a significant proportion of people with mental health problems do not receive these treatments. Finding ways to reduce this treatment gap is crucial. Since app‐supported smartphone interventions are touted as a possible solution, access to up‐to‐date guidance around the evidence base and clinical utility of these interventions is needed. We conducted a meta‐analysis of 66 randomized controlled trials of app‐supported smartphone interventions for mental health problems. Smartphone interventions significantly outperformed control conditions in improving depressive (g=0.28, n=54) and generalized anxiety (g=0.30, n=39) symptoms, stress levels (g=0.35, n=27), quality of life (g=0.35, n=43), general psychiatric distress (g=0.40, n=12), social anxiety symptoms (g=0.58, n=6), and positive affect (g=0.44, n=6), with most effects being robust even after adjusting for various possible biasing factors (type of control condition, risk of bias rating). Smartphone interventions conferred no significant benefit over control conditions on panic symptoms (g=–0.05, n=3), post‐traumatic stress symptoms (g=0.18, n=4), and negative affect (g=–0.08, n=5). Studies that delivered a cognitive behavior therapy (CBT)‐based app and offered professional guidance and reminders to engage produced larger effects on multiple outcomes. Smartphone interventions did not differ significantly from active interventions (face‐to‐face, computerized treatment), although the number of studies was low (n≤13). The efficacy of app‐supported smartphone interventions for common mental health problems was thus confirmed. Although mental health apps are not intended to replace professional clinical services, the present findings highlight the potential of apps to serve as a cost‐effective, easily accessible, and low intensity intervention for those who cannot receive standard psychological treatment.     

Effectiveness of programs for reducing the stigma associated with mental disorders. A meta‐analysis of randomized controlled trials

The stigma associated with mental disorders is a global public health problem. Programs to combat it must be informed by the best available evidence. To this end, a meta‐analysis was undertaken to investigate the effectiveness of existing programs. A systematic search of PubMed, PsycINFO and Cochrane databases yielded 34 relevant papers, comprising 33 randomized controlled trials. Twenty‐seven papers (26 trials) contained data that could be incorporated into a quantitative analysis. Of these trials, 19 targeted personal stigma or social distance (6,318 participants), six addressed perceived stigma (3,042 participants) and three self‐stigma (238 participants). Interventions targeting personal stigma or social distance yielded small but significant reductions in stigma across all mental disorders combined (d=0.28, 95% CI: 0.17‐0.39, p<0.001) as well as for depression (d=0.36, 95% CI: 0.10‐0.60, p<0.01), psychosis (d=0.20, 95% CI: 0.06‐0.34, p<0.01) and generic mental illness (d=0.30, 95% CI: 0.10‐0.50, p<0.01). Educational interventions were effective in reducing personal stigma (d=0.33, 95% CI: 0.19‐0.42, p<0.001) as were interventions incorporating consumer contact (d=0.47, 95% CI: 0.17‐0.78, p<0.001), although there were insufficient studies to demonstrate an effect for consumer contact alone. Internet programs were at least as effective in reducing personal stigma as face‐to‐face delivery. There was no evidence that stigma interventions were effective in reducing perceived or self‐stigma. In conclusion, there is an evidence base to inform the roll out of programs for improving personal stigma among members of the community. However, there is a need to investigate methods for improving the effectiveness of these programs and to develop interventions that are effective in reducing perceived and internalized stigma.     

Psychological interventions to reduce positive symptoms in schizophrenia: systematic review and network meta‐analysis

Psychological treatments are increasingly regarded as useful interventions for schizophrenia. However, a comprehensive evaluation of the available evidence is lacking and the benefit of psychological interventions for patients with current positive symptoms is still debated. The present study aimed to evaluate the efficacy, acceptability and tolerability of psychological treatments for positive symptoms of schizophrenia by applying a network meta‐analysis approach, that can integrate direct and indirect comparisons. We searched EMBASE, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Library, World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov for randomized controlled trials of psychological treatments for positive symptoms of schizophrenia, published up to January 10, 2018. We included studies on adults with a diagnosis of schizophrenia or a related disorder presenting positive symptoms. The primary outcome was change in positive symptoms measured with validated rating scales. We included 53 randomized controlled trials of seven psychological interventions, for a total of 4,068 participants receiving the psychological treatment as add‐on to antipsychotics. On average, patients were moderately ill at baseline. The network meta‐analysis showed that cognitive behavioural therapy (40 studies) reduced positive symptoms more than inactive control (standardized mean difference, SMD=?0.29; 95% CI: –0.55 to ?0.03), treatment as usual (SMD=?0.30; 95% CI: –0.45 to ?0.14) and supportive therapy (SMD=?0.47; 95% CI: –0.91 to ?0.03). Cognitive behavioural therapy was associated with a higher dropout rate compared with treatment as usual (risk ratio, RR=0.74; 95% CI: 0.58 to 0.95). Confidence in the estimates ranged from moderate to very low. The other treatments contributed to the network with a lower number of studies. Results were overall consistent in sensitivity analyses controlling for several factors, including the role of researchers’ allegiance and blinding of outcome assessor. Cognitive behavior therapy seems to be effective on positive symptoms in moderately ill patients with schizophrenia, with effect sizes in the lower to medium range, depending on the control condition.     

Internet and Computer-Based Cognitive Behavioral Therapy for Anxiety and Depression in Youth: A Meta-Analysis of Randomized Controlled Outcome Trials

Background

Anxiety and depression in children and adolescents are undertreated. Computer- and Internet-based cognitive behavioral treatments (cCBT) may be an attractive treatment alternative to regular face-to-face treatment.This meta-analysis aims to evaluate whether cCBT is effective for treating symptoms of anxiety and depression in youth.

Methods and Findings

We conducted systematic searches in bibliographical databases (Pubmed, Cochrane controlled trial register, PsychInfo) up to December 4, 2013. Only randomized controlled trials in which a computer-, Internet- or mobile-based cognitive behavioral intervention targeting either depression, anxiety or both in children or adolescents up to the age of 25 were compared to a control condition were selected. We employed a random-effects pooling model in overall effect analyses and a mixed effect model for sub-group analyses. Searches resulted in identifying 13 randomized trials, including 796 children and adolescents that met inclusion criteria. Seven studies were directed at treating anxiety, four studies at depression, and two were of a transdiagnostic nature, targeting both anxiety and depression. The overall mean effect size (Hedges’ g) of cCBT on symptoms of anxiety or depression at post-test was g=0.72 (95% CI:0.55-0.90, numbers needed to be treated (NNT)=2.56). Heterogeneity was low (I²=20.14%, 95% CI: 0-58%). The superiority of cCBT over controls was evident for interventions targeting anxiety (g=0.68; 95% CI: 0.45-0.92; p < .001; NNT=2.70) and for interventions targeting depression (g=0.76; 95% CI: 0.41-0.12; p < .001; NNT=2.44) as well as for transdiagnostic interventions (g=0.94; 95% CI: 0.23-2.66; p < .001; NNT=2.60).

Conclusions

Results provide evidence for the efficacy of cCBT in the treatment of anxiety and depressive symptoms in youth. Hence, such interventions may be a promising treatment alternative when evidence based face-to-face treatment is not feasible. Future studies should examine long-term effects of treatments and should focus on obtaining patient-level data from existing studies, to perform an individual patient data meta-analysis.     

Bereavement after sibling death: a population‐based longitudinal case‐control study

The objective of this study was to examine mental disorders and treatment use among bereaved siblings in the general population. Siblings (N=7243) of all deceased children in the population of Manitoba, Canada who died between 1984 and 2009 were matched 1:3 to control siblings (N=21,729) who did not have a sibling die in the study period. Generalized estimating equations were used to compare the two sibling groups in the two years before and after the index child's death on physician‐diagnosed mental disorders and treatment utilization, with adjustment for confounding factors including pre‐existing mental illness. Analyses were stratified by age of the bereaved (<13 vs. 13+). Results revealed that, in the two years after the death of the child, bereaved siblings had significantly higher rates of mental disorders than control siblings, even after adjusting for pre‐existing mental illness. When comparing the effect of a child's death on younger versus older siblings, the rise in depression rates from pre‐death to post‐death was significantly higher for siblings aged under 13 (p<0.0001), increasing more than 7‐fold (adjusted relative rate, ARR=7.25, 95% CI: 3.65‐14.43). Bereaved siblings aged 13+ had substantial morbidity in the two years after the death: 25% were diagnosed with a mental disorder (vs. 17% of controls), and they had higher rates of almost all mental disorder outcomes compared to controls, including twice the rate of suicide attempts (ARR=2.01, 95% CI: 1.29‐3.12). Siblings in the bereaved cohort had higher rates of alcohol and drug use disorders already before the death of their sibling. In conclusion, the death of a child is associated with considerable mental disorder burden among surviving siblings. Pre‐existing health problems and social disadvantage do not fully account for the increase in mental disorder rates.     

Increased risk of COVID‐19 infection and mortality in people with mental disorders: analysis from electronic health records in the United States

Concerns have been expressed that persons with a pre‐existing mental disorder may represent a population at increased risk for COVID‐19 infec­tion and with a higher likelihood of adverse outcomes of the infection, but there is no systematic research evidence in this respect. This study assessed the impact of a recent (within past year) diagnosis of a mental disorder – including attention‐deficit/hyperactivity disorder (ADHD), bipolar disorder, depression and schizophrenia – on the risk for COVID‐19 infection and related mortality and hospitalization rates. We analyzed a nation‐wide database of electronic health records of 61 million adult patients from 360 hospitals and 317,000 providers, across 50 states in the US, up to July 29, 2020. Patients with a recent diagnosis of a mental disorder had a significantly increased risk for COVID‐19 infection, an effect strongest for depression (adjusted odds ratio, AOR=7.64, 95% CI: 7.45‐7.83, p<0.001) and schizophrenia (AOR=7.34, 95% CI: 6.65‐8.10, p<0.001). Among patients with a recent diagnosis of a mental disorder, African Americans had higher odds of COVID‐19 infection than Caucasians, with the strongest ethnic disparity for depression (AOR=3.78, 95% CI: 3.58‐3.98, p<0.001). Women with mental disorders had higher odds of COVID‐19 infection than males, with the strongest gender disparity for ADHD (AOR=2.03, 95% CI: 1.73‐2.39, p<0.001). Patients with both a recent diagnosis of a mental disorder and COVID‐19 infection had a death rate of 8.5% (vs. 4.7% among COVID‐19 patients with no mental disorder, p<0.001) and a hospitalization rate of 27.4% (vs. 18.6% among COVID‐19 patients with no mental disorder, p<0.001). These findings identify individuals with a recent diagnosis of a mental disorder as being at increased risk for COVID‐19 infection, which is further exacerbated among African Americans and women, and as having a higher frequency of some adverse outcomes of the infection. This evidence highlights the need to identify and address modifiable vulnerability factors for COVID‐19 infection and to prevent delays in health care provision in this population.     

Cognitive behavior therapy vs. control conditions,other psychotherapies,pharmacotherapies and combined treatment for depression: a comprehensive meta-analysis including 409 trials with 52,702 patients

Cognitive behavior therapy (CBT) is by far the most examined type of psychological treatment for depression and is recommended in most treatment guide­lines. However, no recent meta-analysis has integrated the results of randomized trials examining its effects, and its efficacy in comparison with other psychotherapies, pharmacotherapies and combined treatment for depression remains uncertain. We searched PubMed, PsycINFO, Embase and the Cochrane Library to identify studies on CBT, and separated included trials into several subsets to conduct random-effects meta-analyses. We included 409 trials (518 comparisons) with 52,702 patients, thus conducting the largest meta-analysis ever of a specific type of psychotherapy for a mental disorder. The quality of the trials was found to have increased significantly over time (with increasing numbers of trials with low risk of bias, less waitlist control groups, and larger sample sizes). CBT had moderate to large effects compared to control conditions such as care as usual and waitlist (g=0.79; 95% CI: 0.70-0.89), which remained similar in sensitivity analyses and were still significant at 6-12 month follow-up. There was no reduction of the effect size of CBT according to the publication year (<2001 vs. 2001-2010 vs. >2011). CBT was significantly more effective than other psychotherapies, but the difference was small (g=0.06; 95% CI: 0-0.12) and became non-significant in most sensitivity analyses. The effects of CBT did not differ significantly from those of pharmacotherapies at the short term, but were significantly larger at 6-12 month follow-up (g=0.34; 95% CI: 0.09-0.58), although the number of trials was small, and the difference was not significant in all sensitivity analyses. Combined treatment was more effective than pharmacotherapies alone at the short (g=0.51; 95% CI: 0.19-0.84) and long term (g=0.32; 95% CI: 0.09-0.55), but it was not more effective than CBT alone at either time point. CBT was also effective as unguided self-help intervention (g=0.45; 95% CI: 0.31-0.60), in institutional settings (g=0.65; 95% CI: 0.21-1.08), and in children and adolescents (g=0.41; 95% CI: 0.25-0.57). We can conclude that the efficacy of CBT in depression is documented across different formats, ages, target groups, and settings. However, the superiority of CBT over other psychotherapies for depression does not emerge clearly from this meta-analysis. CBT appears to be as effective as pharmacotherapies at the short term, but more effective at the longer term.     

Psychotherapies for depression in low‐ and middle‐income countries: a meta‐analysis

Most psychotherapies for depression have been developed in high‐income Western countries of North America, Europe and Australia. A growing number of randomized trials have examined the effects of these treatments in non‐Western countries. We conducted a meta‐analysis of these studies to examine whether these psychotherapies are effective and to compare their effects between studies from Western and non‐Western countries. We conducted systematic searches in bibliographical databases and included 253 randomized controlled trials, of which 32 were conducted in non‐Western countries. The effects of psychotherapies in non‐Western countries were large (g=1.10; 95% CI: 0.91‐1.30), with high heterogeneity (I²=90; 95% CI: 87‐92). After adjustment for publication bias, the effect size dropped to g=0.73 (95% CI: 0.51‐0.96). Subgroup analyses did not indicate that adaptation to the local situation was associated with the effect size. Comparisons with the studies in Western countries showed that the effects of the therapies were significantly larger in non‐Western countries, also after adjusting for characteristics of the participants, the treatments and the studies. These larger effect sizes in non‐Western countries may reflect true differences indicating that therapies are indeed more effective; or may be explained by the care‐as‐usual control conditions in non‐Western countries, often indicating that no care was available; or may be the result of the relative low quality of many trials in the field. This study suggests that psychotherapies that were developed in Western countries may or may not be more effective in non‐Western countries, but they are probably no less effective and can therefore also be used in these latter countries.     

Self‐Reported Body Mass Index and Health‐Related Quality of Life: Findings from the Behavioral Risk Factor Surveillance System

Objective: To examine the relationship between self‐reported body mass index (BMI) and health‐related quality of life in the general adult population in the United States. Research Methods and Procedures: Using data from 109,076 respondents in the 1996 Behavioral Risk Factor Surveillance System, we examined how self‐reported BMI is associated with five health‐related quality of life measures developed by the Centers for Disease Control and Prevention for population health surveillance. Results: After adjusting for age, gender, race or ethnicity, educational attainment, employment status, smoking status, and physical activity status, participants with a self‐reported BMI of <18.5 kg/m² and participants with a self‐reported BMI of ≥30 kg/m² reported impaired quality of life. Compared with persons with a self‐reported BMI of 18.5 to <25 kg/m², odds ratios (ORs) of poor or fair self‐rated health increased among persons with self‐reported BMIs of <18.5 (1.57, 95% confidence interval [CI]: 1.31 to 1.89), 25 to <30 kg/m² (1.12, 95% CI: 1.04 to 1.20), 30 to <35 kg/m² (1.65, 95% CI: 1.50 to 1.81), 35 to <40 kg/m² (2.58, 95% CI: 2.21 to 3.00), and ≥40 kg/m² (3.23, 95% CI: 2.63 to 3.95); ORs for reporting ≥14 days of poor physical health during the previous 30 days were 1.44 (95% CI: 1.21 to 1.72), 1.04 (95% CI: 0.96 to 1.14), 1.32 (95% CI: 1.19 to 1.47), 1.80 (95% CI: 1.52 to 2.13), and 2.37 (95% CI: 1.90 to 2.94), respectively; ORs for having ≥14 days of poor mental health during the previous 30 days were 1.18 (95% CI: 0.97 to 1.42), 1.02 (95% CI: 0.95 to 1.11), 1.22 (95% CI: 1.10 to 1.36), 1.68 (95% CI: 1.42 to 1.98), and 1.66 (95% CI: 1.32 to 2.09), respectively. Discussion: In the largest study to date, low and increased self‐reported BMI significantly impaired health‐related quality of life. Particularly, deviations from normal BMI affected physical functioning more strongly than mental functioning.     

Delivering interventions for depression by using the internet: randomised controlled trial

Objective To evaluate the efficacy of two internet interventions for community-dwelling individuals with symptoms of depression—a psychoeducation website offering information about depression and an interactive website offering cognitive behaviour therapy.Design Randomised controlled trial.Setting Internet users in the community, in Canberra, Australia.Participants 525 individuals with increased depressive symptoms recruited by survey and randomly allocated to a website offering information about depression (n = 166) or a cognitive behaviour therapy website (n = 182), or a control intervention using an attention placebo (n = 178).Main outcome measures Change in depression, dysfunctional thoughts; knowledge of medical, psychological, and lifestyle treatments; and knowledge of cognitive behaviour therapy.Results Intention to treat analyses indicated that information about depression and interventions that used cognitive behaviour therapy and were delivered via the internet were more effective than a credible control intervention in reducing symptoms of depression in a community sample. For the intervention that delivered cognitive behaviour therapy the reduction in score on the depression scale of the Center for Epidemiologic Studies was 3.2 (95% confidence interval 0.9 to 5.4). For the “depression literacy” site (BluePages), the reduction was 3.0 (95% confidence interval 0.6 to 5.2). Cognitive behaviour therapy (MoodGYM) reduced dysfunctional thinking and increased knowledge of cognitive behaviour therapy. Depression literacy (BluePages) significantly improved participants'' understanding of effective evidence based treatments for depression (P < 0.05).Conclusions Both cognitive behaviour therapy and psychoeducation delivered via the internet are effective in reducing symptoms of depression.     

Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review,meta‐analysis and meta‐regression analysis

Antipsychotic polypharmacy in schizophrenia is much debated, since it is common and costly with unclear evidence for its efficacy and safety. We conducted a systematic literature search and a random effects meta‐analysis of randomized trials comparing augmentation with a second antipsychotic vs. continued antipsychotic monotherapy in schizophrenia. Co‐primary outcomes were total symptom reduction and study‐defined response. Antipsychotic augmentation was superior to monotherapy regarding total symptom reduction (16 studies, N=694, standardized mean difference, SMD=–0.53, 95% CI: ?0.87 to ?0.19, p=0.002). However, superiority was only apparent in open‐label and low‐quality trials (both p<0.001), but not in double‐blind and high‐quality ones (p=0.120 and 0.226, respectively). Study‐defined response was similar between antipsychotic augmentation and monotherapy (14 studies, N=938, risk ratio = 1.19, 95% CI: 0.99 to 1.42, p=0.061), being clearly non‐significant in double‐blind and high‐quality studies (both p=0.990). Findings were replicated in clozapine and non‐clozapine augmentation studies. No differences emerged regarding all‐cause/specific‐cause discontinuation, global clinical impression, as well as positive, general and depressive symptoms. Negative symptoms improved more with augmentation treatment (18 studies, N=931, SMD=–0.38, 95% CI: ?0.63 to ?0.13, p<0.003), but only in studies augmenting with aripiprazole (8 studies, N=532, SMD=–0.41, 95% CI: ?0.79 to ?0.03, p=0.036). Few adverse effect differences emerged: D2 antagonist augmentation was associated with less insomnia (p=0.028), but more prolactin elevation (p=0.015), while aripiprazole augmentation was associated with reduced prolactin levels (p<0.001) and body weight (p=0.030). These data suggest that the common practice of antipsychotic augmentation in schizophrenia lacks double‐blind/high‐quality evidence for efficacy, except for negative symptom reduction with aripiprazole augmentation.     

Prevalence,incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large‐scale meta‐analysis of 3,211,768 patients and 113,383,368 controls

People with severe mental illness (SMI) – schizophrenia, bipolar disorder and major depressive disorder – appear at risk for cardiovascular disease (CVD), but a comprehensive meta‐analysis is lacking. We conducted a large‐scale meta‐analysis assessing the prevalence and incidence of CVD; coronary heart disease; stroke, transient ischemic attack or cerebrovascular disease; congestive heart failure; peripheral vascular disease; and CVD‐related death in SMI patients (N=3,211,768) versus controls (N=113,383,368) (92 studies). The pooled CVD prevalence in SMI patients (mean age 50 years) was 9.9% (95% CI: 7.4‐13.3). Adjusting for a median of seven confounders, patients had significantly higher odds of CVD versus controls in cross‐sectional studies (odds ratio, OR=1.53, 95% CI: 1.27‐1.83; 11 studies), and higher odds of coronary heart disease (OR=1.51, 95% CI: 1.47‐1.55) and cerebrovascular disease (OR=1.42, 95% CI: 1.21‐1.66). People with major depressive disorder were at increased risk for coronary heart disease, while those with schizophrenia were at increased risk for coronary heart disease, cerebrovascular disease and congestive heart failure. Cumulative CVD incidence in SMI patients was 3.6% (95% CI: 2.7‐5.3) during a median follow‐up of 8.4 years (range 1.8‐30.0). Adjusting for a median of six confounders, SMI patients had significantly higher CVD incidence than controls in longitudinal studies (hazard ratio, HR=1.78, 95% CI: 1.60‐1.98; 31 studies). The incidence was also higher for coronary heart disease (HR=1.54, 95% CI: 1.30‐1.82), cerebrovascular disease (HR=1.64, 95% CI: 1.26‐2.14), congestive heart failure (HR=2.10, 95% CI: 1.64‐2.70), and CVD‐related death (HR=1.85, 95% CI: 1.53‐2.24). People with major depressive disorder, bipolar disorder and schizophrenia were all at increased risk of CVD‐related death versus controls. CVD incidence increased with antipsychotic use (p=0.008), higher body mass index (p=0.008) and higher baseline CVD prevalence (p=0.03) in patients vs. controls. Moreover, CVD prevalence (p=0.007), but not CVD incidence (p=0.21), increased in more recently conducted studies. This large‐scale meta‐analysis confirms that SMI patients have significantly increased risk of CVD and CVD‐related mortality, and that elevated body mass index, antipsychotic use, and CVD screening and management require urgent clinical attention.     

Sedentary behavior and physical activity levels in people with schizophrenia,bipolar disorder and major depressive disorder: a global systematic review and meta‐analysis

People with severe mental illness (schizophrenia, bipolar disorder or major depressive disorder) die up to 15 years prematurely due to chronic somatic comorbidities. Sedentary behavior and low physical activity are independent yet modifiable risk factors for cardiovascular disease and premature mortality in these people. A comprehensive meta‐analysis exploring these risk factors is lacking in this vulnerable population. We conducted a meta‐analysis investigating sedentary behavior and physical activity levels and their correlates in people with severe mental illness. Major electronic databases were searched from inception up to April 2017 for articles measuring sedentary behavior and/or physical activity with a self‐report questionnaire or an objective measure (e.g., accelerometer). Random effects meta‐analyses and meta‐regression analyses were conducted. Sixty‐nine studies were included (N=35,682; 39.5% male; mean age 43.0 years). People with severe mental illness spent on average 476.0 min per day (95% CI: 407.3‐545.4) being sedentary during waking hours, and were significantly more sedentary than age‐ and gender‐matched healthy controls (p=0.003). Their mean amount of moderate or vigorous physical activity was 38.4 min per day (95% CI: 32.0‐44.8), being significantly lower than that of healthy controls (p=0.002 for moderate activity, p<0.001 for vigorous activity). People with severe mental illness were significantly less likely than matched healthy controls to meet physical activity guidelines (odds ratio = 1.5; 95% CI: 1.1‐2.0, p<0.001, I²=95.8). Lower physical activity levels and non‐compliance with physical activity guidelines were associated with male gender, being single, unemployment, fewer years of education, higher body mass index, longer illness duration, antidepressant and antipsychotic medication use, lower cardiorespiratory fitness and a diagnosis of schizophrenia. People with bipolar disorder were the most physically active, yet spent most time being sedentary. Geographical differences were detected, and inpatients were more active than outpatients and those living in the community. Given the established health benefits of physical activity and its low levels in people with severe mental illness, future interventions specifically targeting the prevention of physical inactivity and sedentary behavior are warranted in this population.     

A network meta‐analysis of the effects of psychotherapies,pharmacotherapies and their combination in the treatment of adult depression

No network meta‐analysis has examined the relative effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression, while this is a very important clinical issue. We conducted systematic searches in bibliographical databases to identify randomized trials in which a psychotherapy and a pharmacotherapy for the acute or long‐term treatment of depression were compared with each other, or in which the combination of a psychotherapy and a pharmacotherapy was compared with either one alone. The main outcome was treatment response (50% improvement between baseline and endpoint). Remission and acceptability (defined as study drop‐out for any reason) were also examined. Possible moderators that were assessed included chronic and treatment‐resistant depression and baseline severity of depression. Data were pooled as relative risk (RR) using a random‐effects model. A total of 101 studies with 11,910 patients were included. Depression in most studies was moderate to severe. In the network meta‐analysis, combined treatment was more effective than psychotherapy alone (RR=1.27; 95% CI: 1.14‐1.39) and pharmacotherapy alone (RR=1.25; 95% CI: 1.14‐1.37) in achieving response at the end of treatment. No significant difference was found between psychotherapy alone and pharmacotherapy alone (RR=0.99; 95% CI: 0.92‐1.08). Similar results were found for remission. Combined treatment (RR=1.23; 95% CI: 1.05‐1.45) and psychotherapy alone (RR=1.17; 95% CI: 1.02‐1.32) were more acceptable than pharmacotherapy. Results were similar for chronic and treatment‐resistant depression. The combination of psychotherapy and pharmacotherapy seems to be the best choice for patients with moderate depression. More research is needed on long‐term effects of treatments (including cost‐effectiveness), on the impact of specific pharmacological and non‐pharmacological approaches, and on the effects in specific populations of patients.     

Guided Internet‐based vs. face‐to‐face cognitive behavior therapy for psychiatric and somatic disorders: a systematic review and meta‐analysis

Internet-delivered cognitive behavior therapy (ICBT) has been tested in many research trials, but to a lesser extent directly compared to face-to-face delivered cognitive behavior therapy (CBT). We conducted a systematic review and meta-analysis of trials in which guided ICBT was directly compared to face-to-face CBT. Studies on psychiatric and somatic conditions were included. Systematic searches resulted in 13 studies (total N=1053) that met all criteria and were included in the review. There were three studies on social anxiety disorder, three on panic disorder, two on depressive symptoms, two on body dissatisfaction, one on tinnitus, one on male sexual dysfunction, and one on spider phobia. Face-to-face CBT was either in the individual format (n=6) or in the group format (n=7). We also assessed quality and risk of bias. Results showed a pooled effect size (Hedges'' g) at post-treatment of −0.01 (95% CI: −0.13 to 0.12), indicating that guided ICBT and face-to-face treatment produce equivalent overall effects. Study quality did not affect outcomes. While the overall results indicate equivalence, there are still few studies for each psychiatric and somatic condition and many conditions for which guided ICBT has not been compared to face-to-face treatment. Thus, more research is needed to establish equivalence of the two treatment formats.     

Depression in Medical School: The Influence of Morningness‐Eveningness

Medical students are at higher risk for depression, affecting not only their lives but also patient care. This article studied a population of medical students engaged in lecture‐based learning regarding the presence of depressive symptoms and its relation to morningness‐eveningness. Depressive symptoms were assessed by the Beck Depressive Inventory scale (BDI>10), and diurnal preference was assessed by the Horne & Östberg Morningness/Eveningness Questionnaire (MEQ). Family history of depression and involvement in regular physical activity were also investigated. A total of 161 students, 77 (47.8%) males, aged 19 to 30 yrs (22.1±2.1) living in a city close to the equator were evaluated. Fifty‐three individuals (32.9%) had depressive symptoms. Depressive individuals showed a trend to be female (p=0.07). Also, female gender showed a non‐significant shift toward morningness. Fifty‐eight (36.0%) subjects participated in regular physical activity. In 57 cases (35.4%), there was a history of depression in the family. Fifteen individuals (9.3%) were definitely evening type, 42 (26.1%) were moderately evening type, 44 (27.3%) were indifferent, 42 (26.1%) were moderately morning type, and 18 (11.2%) were definitely morning type. Family history of depression (OR=0.29, 95% CI=1.37–6.12) and sedentary life (OR=0.28, 95% CI=0.12–0.65) were associated with depressive symptoms. Eveningness was associated with depressive symptoms (OR=0.66, 95% CI=0.50–0.88), and this association remained significant after adjusting for the presence of familial depression and physical activity (OR=0.71, 95% CI=0.52–0.95). In conclusion, depressive symptoms are independently associated with “eveningness” in medical students. These results should be confirmed by future studies involving a larger number of subjects.     

The SHED‐IT Randomized Controlled Trial: Evaluation of an Internet‐based Weight‐loss Program for Men

The aim of this study was to evaluate the efficacy of an Internet‐based weight‐loss program for men in an assessor blinded randomized controlled trial. In total, 65 overweight/obese male staff and students at the University of Newcastle (mean (s.d.) age = 35.9 (11.1) years; BMI = 30.6 (2.8)) were randomly assigned to either (i) Internet group (n = 34) or (ii) control group (information only) (n = 31). Both groups received one face‐to‐face information session and a program booklet. Internet group participants used the study website to self‐monitor diet and activity with feedback provided based on participants' online entries on seven occasions over 3 months. Participants were assessed at baseline, 3‐, and 6‐month follow‐up for weight, waist circumference, BMI, blood pressure, resting heart rate, objectively measured physical activity, and self‐reported total daily kilojoules. Intention‐to‐treat analysis revealed significant weight loss of 5.3 kg (95% confidence interval (CI): ?7.3, ?3.3) at 6 months for the Internet group and 3.5 kg (95% CI: ?5.5, ?1.4) for the control group. A significant time effect was found for all outcomes but no between‐group differences. Per‐protocol analysis revealed a significant group‐by‐time interaction (P < 0.001), with compliers losing more weight at 6 months (?9.1 kg; 95% CI ?11.8, ?6.5) than noncompliers (?2.7 kg; 95% CI ?5.3, ?0.01) and the control group (?4.2 kg; 95% CI ?6.2, ?2.2). Simple weight‐loss interventions can be effective in achieving statistically and clinically significant weight loss in men. The Internet is a feasible and effective medium for weight loss in men but strategies need to be explored to improve engagement in online programs.     

Tardive dyskinesia risk with first‐ and second‐generation antipsychotics in comparative randomized controlled trials: a meta‐analysis

Tardive dyskinesia (TD) risk with D2/serotonin receptor antagonists or D2 receptor partial agonists (second‐generation antipsychotics, SGAs) is considered significantly lower than with D2 antagonists (first‐generation antipsychotics, FGAs). As some reports questioned this notion, we meta‐analyzed randomized controlled studies (RCTs) to estimate the risk ratio (RR) and annualized rate ratio (RaR) of TD comparing SGAs vs. FGAs and SGAs vs. SGAs. Additionally, we calculated raw and annualized pooled TD rates for each antipsychotic. Data from 57 head‐to‐head RCTs, including 32 FGA and 86 SGA arms, were meta‐analyzed, yielding 32 FGA‐SGA pairs and 35 SGA‐SGA pairs. The annualized TD incidence across FGA arms was 6.5% (95% CI: 5.3‐7.8%) vs. 2.6% (95% CI: 2.0‐3.1%) across SGA arms. TD risk and annualized rates were lower with SGAs vs. FGAs (RR=0.47, 95% CI: 0.39‐0.57, p<0.0001, k=28; RaR=0.35, 95% CI: 0.28‐0.45, p<0.0001, number‐needed‐to‐treat, NNT=20). Meta‐regression showed no FGA dose effect on FGA‐SGA comparisons (Z=?1.03, p=0.30). FGA‐SGA TD RaRs differed by SGA comparator (Q=21.8, df=7, p=0.003), with a significant advantage of olanzapine and aripiprazole over other non‐clozapine SGAs in exploratory pairwise comparisons. SGA‐SGA comparisons confirmed the olanzapine advantage vs. non‐clozapine SGAs (RaR=0.66, 95% CI: 0.49‐0.88, p=0.006, k=17, NNT=100). This meta‐analysis confirms a clinically meaningfully lower TD risk with SGAs vs. FGAs, which is not driven by high dose FGA comparators, and documents significant differences with respect to this risk between individual SGAs.     

World Health Organization's low-intensity psychosocial interventions: a systematic review and meta-analysis of the effects of Problem Management Plus and Step-by-Step

Many societies have been recently exposed to humanitarian and health emergencies, which have resulted in a large number of people experiencing significant distress and being at risk to develop mental disorders such as depression, anxiety and post-traumatic stress disorder. The World Health Organization has released a series of scalable psychosocial interventions for people impaired by distress in communities exposed to adversities. Prominent among these is a low-intensity transdiagnostic psychosocial intervention, Problem Management Plus (PM+), and its digital adaptation Step-by-Step (SbS). This systematic review is the first to summarize the available evidence on the effects of PM+ and SbS. Up to March 8, 2023, five databases were searched for randomized controlled trials examining the effects of PM+ or SbS on distress indicators (i.e., general distress; anxiety, depressive or post-traumatic stress disorder symptoms; functional impairment, self-identified problems) and positive mental health outcomes (i.e., well-being, quality of life, social support/relationships). We performed random-effects multilevel meta-analyses on standardized mean differences (SMDs) at post-intervention and short-term follow-up assessments. Our search yielded 23 eligible studies, including 5,298 participants. We found a small to medium favorable effect on distress indicators (SMD=–0.45, 95% CI: –0.56 to –0.34) and a small beneficial effect on positive mental health outcomes (SMD=0.31, 95% CI: 0.14-0.47), which both remained significant at follow-up assessment and were robust in sensitivity analyses. However, our analyses pointed to substantial between-study heterogeneity, which was only partially explained by moderators, and the certainty of evidence was very low across all outcomes. These results provide evidence for the effectiveness of PM+ and SbS in reducing distress indicators and promoting positive mental health in populations exposed to adversities, but a larger high-quality evidence base is needed, as well as research on participant-level moderators of the effects of these interventions, their suitability for stepped-care programs, and their cost-effectiveness.     

Symbolic sequence learning is associated with cognitive–affective profiles in female FMR1 premutation carriers

This study examines implicit sequence learning impairments that may indicate at‐risk cerebellar profiles proposed to underlie some aspects of subtle cognitive and affective dysfunctions found among female fragile X mental retardation 1 (FMR1) premutation (PM)‐carriers. A total of 34 female PM‐carriers and 33 age‐ and intelligence‐matched controls completed an implicit symbolically primed serial reaction time task (SRTT) previously shown to be sensitive to cerebellar involvement. Implicit learning scores indicated a preservation of learning in both groups; however, PM‐carriers demonstrated poorer learning through significantly elevated response latencies overall and at each specific block within the symbolic SRTT. Group comparisons also revealed a core deficit in response inhibition, alongside elevated inattentive symptoms in female PM‐carriers. Finally, strong and significant associations were observed between poor symbolic SRTT performance and executive, visuospatial and affective deficits in the PM‐carrier group. These associations remained strong even after controlling motor speed, and were not observed in age‐ and intelligence quotient‐matched participants. The findings implicate cerebellar non‐motor networks subserving the implicit sequencing of responses in cognitive–affective phenotypes previously observed in female PM‐carriers. We contend that symbolic SRTT performance may offer clinical utility in future pharmaceutical interventions in female PM‐carriers .