Statins for the treatment of depression: a meta-analysis of randomized, double-blind, placebo-controlled trials

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

N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis

OBJECTIVE: To assess the utility of N-acetylcysteine administration for depressive symptoms in subjects with psychiatric conditions using a systematic review and meta-analysis. DATA SOURCES: A computerized literature search was conducted in MEDLINE, Embase, the Cochrane Library, SciELO, PsycINFO, Scopus, and Web of Knowledge. No year or country restrictions were used. The Boolean terms used for the electronic database search were (NAC OR N-acetylcysteine OR acetylcysteine) AND (depression OR depressive OR depressed) AND (trial). The last search was performed in November 2014. STUDY SELECTION: The literature was searched for double-blind, randomized, placebo-controlled trials using N-acetylcysteine for depressive symptoms regardless of the main psychiatric condition. Using keywords and cross-referenced bibliographies, 38 studies were identified and examined in depth. Of those, 33 articles were rejected because inclusion criteria were not met. Finally, 5 studies were included. DATA EXTRACTION: Data were extracted independently by 2 investigators. The primary outcome measure was change in depressive symptoms. Functionality, quality of life, and manic and anxiety symptoms were also examined. A full review and meta-analysis were performed. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% CIs were calculated. RESULTS: Five studies fulfilled our inclusion criteria for the meta-analysis, providing data on 574 participants, of whom 291 were randomized to receive N-acetylcysteine and 283 to placebo. The follow-up varied from 12 to 24 weeks. Two studies included subjects with bipolar disorder and current depressive symptoms, 1 included subjects with MDD in a current depressive episode, and 2 included subjects with depressive symptoms in the context of other psychiatric conditions (1 trichotillomania and 1 heavy smoking). Treatment with N-acetylcysteine improved depressive symptoms as assessed by Montgomery-Asberg Depression Rating Scale and Hamilton Depression Rating Scale when compared to placebo (SMD = 0.37; 95% CI = 0.19 to 0.55; P < .001). Subjects receiving N-acetylcysteine had better depressive symptoms scores on the Clinical Global Impressions-Severity of Illness scale at follow-up than subjects on placebo (SMD = 0.22; 95% CI = 0.03 to 0.41; P < .001). In addition, global functionality was better in N-acetylcysteine than in placebo conditions. There were no changes in quality of life. With regard to adverse events, only minor adverse events were associated with N-acetylcysteine (OR = 1.61; 95% CI = 1.01 to 2.59; P = .049). CONCLUSIONS: Administration of N-acetylcysteine ameliorates depressive symptoms, improves functionality, and shows good tolerability.

Effectiveness of interventions targeting physical activity, nutrition and healthy weight for university and college students: a systematic review and meta-analysis

To examine the effectiveness of interventions aimed at improving physical activity, diet, and/or weight-related behaviors amongst university/college students. Five online databases were searched (January 1970 to April 2014). Experimental study designs were eligible for inclusion. Data extraction was performed by one reviewer using a standardized form developed by the researchers and checked by a second reviewer. Data were described in a narrative synthesis and meta-analyses were conducted when appropriate. Study quality was also established. Forty-one studies were included; of these, 34 reported significant improvements in one of the key outcomes. Of the studies examining physical activity 18/29 yielded significant results, with meta-analysis demonstrating significant increases in moderate physical activity in intervention groups compared to control. Of the studies examining nutrition, 12/24 reported significantly improved outcomes; only 4/12 assessing weight loss outcomes found significant weight reduction. This appears to be the first systematic review of physical activity, diet and weight loss interventions targeting university and college students. Tertiary institutions are appropriate settings for implementing and evaluating lifestyle interventions, however more research is needed to improve such strategies.

High-intensity interval training for improving health-related fitness in adolescents: a systematic review and meta-analysis

BACKGROUND: High-intensity interval training (HIIT) may be a feasible and efficacious strategy for improving health-related fitness in young people. The objective of this systematic review and meta-analysis was to evaluate the utility of HIIT to improve health-related fitness in adolescents and to identify potential moderators of training effects. METHODS: Studies were considered eligible if they: (1) examined adolescents (13-18 years); (2) examined health-related fitness outcomes; (3) involved an intervention of ≥4 weeks in duration; (4) included a control or moderate intensity comparison group; and (5) prescribed high-intensity activity for the HIIT condition. Meta-analyses were conducted to determine the effect of HIIT on health-related fitness components using Comprehensive Meta-analysis software and potential moderators were explored (ie, study duration, risk of bias and type of comparison group). RESULTS: The effects of HIIT on cardiorespiratory fitness and body composition were large, and medium, respectively. Study duration was a moderator for the effect of HIIT on body fat percentage. Intervention effects for waist circumference and muscular fitness were not statistically significant. CONCLUSIONS: HIIT is a feasible and time-efficient approach for improving cardiorespiratory fitness and body composition in adolescent populations.

A combination of omega-3 fatty acids, folic acid and B-group vitamins is superior at lowering homocysteine than omega-3 alone: a meta-analysis

The aim of the study was to assess whether omega-3 polyunsaturated fatty acid supplementation alone or in combination with folic acid and B-group vitamins is effective in lowering homocysteine. The Medline Ovid, Embase and Cochrane databases were searched for randomized-controlled trial studies that intervened with omega-3 supplementation (with or without folic acid) and measured changes in homocysteine concentration. Studies were pooled using a random effects model for meta-analysis. Three different models were analyzed: all trials combined, omega-3 polyunsaturated fatty acid trials, and omega-3 polyunsaturated fatty acids with folic acid and B-group vitamin trials. Nineteen studies were included, consisting of 3267 participants completing 21 trials. Studies were heterogeneous; varying by dose, duration and participant health conditions. Across all trials, omega-3 supplementation was effective in lowering homocysteine by an average of 1.18μmol/L (95%CI: (-1.89, -0.48), P=.001). The average homocysteine-lowering effect was greater when omega-3 supplementation was combined with folic acid and B-group vitamins (-1.37μmol/L, 95%CI: (-2.38, -0.36), P<.01) compared to omega-3 supplementation alone (-1.09μmol/L 95%CI: (-2.04, -0.13), P=.03). Omega-3 polyunsaturated fatty acid supplementation was associated with a modest reduction in homocysteine. For the purposes of reducing homocysteine, a combination of omega-3s (0.2-6g/day), folic acid (150 - 2500μg/day) and vitamins B6 and B12 may be more effective than omega-3 supplementation alone.

Additional weekend therapy may reduce length of rehabilitation stay after stroke: a meta-analysis of individual patient data

QUESTIONS: Among people receiving inpatient rehabilitation after stroke, does additional weekend physiotherapy and/or occupational therapy reduce the length of rehabilitation hospital stay compared to those who receive a weekday-only service, and does this change after controlling for individual factors? Does additional weekend therapy improve the ability to walk and perform activities of daily living, measured at discharge? Does additional weekend therapy improve health-related quality of life, measured 6 months after discharge from rehabilitation? Which individual, clinical and hospital characteristics are associated with shorter length of rehabilitation hospital stay? DESIGN: This study pooled individual data from two randomised, controlled trials (n=350) using an individual patient data meta-analysis and multivariate regression. PARTICIPANTS: People with stroke admitted to inpatient rehabilitation facilities. INTERVENTION: Additional weekend therapy (physiotherapy and/or occupational therapy) compared to usual care (5 days/week therapy). OUTCOME MEASURES: Length of rehabilitation hospital stay, independence in activities of daily living measured with the Functional Independence Measure, walking speed and health-related quality of life. RESULTS: Participants who received weekend therapy had a shorter length of rehabilitation hospital stay. In the un-adjusted analysis, this was not statistically significant (MD -5.7 days, 95% CI -13.0 to 1.5). Controlling for hospital site, age, walking speed and Functional Independence Measure score on admission, receiving weekend therapy was significantly associated with a shorter length of rehabilitation hospital stay (β=7.5, 95% CI 1.7 to 13.4, p=0.001). There were no significant between-group differences in Functional Independence Measure scores (MD 1.9 points, 95% CI -2.8 to 6.6), walking speed (MD 0.06 m/second, 95% CI -0.15 to 0.04) or health-related quality of life (SMD -0.04, 95% CI -0.26 to 0.19) at discharge. DISCUSSION: Modest evidence indicates that additional weekend therapy might reduce rehabilitation hospital length of stay.

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants. Protocol PROSPERO registration number: CRD42013005464.

Efficacy and safety of thrombin-receptor antagonist (atopaxar and vorapaxar) in patients with acute coronary syndrome or coronary artery disease-a meta-analysis of randomized controlled trials

Background: Meta-analysis for the efficacy and safety data of thrombin-receptor antagonist (TRA) based on patients with acute coronary syndrome (ACS) or coronary artery disease (CAD) and indirect comparisons between TRAs were not available. Objectives: We intended to synthesize the primary end points based on different patient populations (ACS or CAD) as well as perform indirect comparison between two newly invented antiplatelet agents atopaxar and vorapaxar. Methods: A literature search was performed in MEDLINE, Embase, and Cochrane Library. Incidences of major adverse cardiovascular events (MACEs) and bleeding events according to thrombolysis in myocardial infarction were selected as primary outcomes, whereas adverse effects were considered as secondary outcomes. Corresponding results were synthesized using Revman 5.1 according to ACS or CAD cohorts. Results: Among the seven included randomized controlled trials, the efficacy end points in the TRA treatment group were favorable compared with placebo. Specifically, the odds ratio (OR) of MACEs was 0.80 (95% confidence interval [CI] 0.52-1.22) for patients with ACS and 0.74 (95% CI 0.53-1.05) for the cohort with CAD. The events of bleeding were unanimously superior in the placebo arm for both cohorts. The indirect comparison showed a superior trend in favor of atopaxar over vorapaxar in occurrences of MACEs (OR 0.93; 95% CI 0.38-1.32), myocardial infarction (OR 0.52; 95% CI 0.13-0.95), and cardiovascular death (OR 0.82; 95% CI 0.12-4.24) and caused less incidence of bleeding. Conclusions: Besides being more effective than placebo in improving the incidence of MACEs but with a higher risk of bleeding, TRAs may exert different effects in patients with ACS and CAD. Indirect comparisons also suggested that atopaxar might be better than vorapaxar in lowering the incidence of MACEs, myocardial infarction, and cardiovascular death and at the same time with lower risks of bleeding.

The State of our Toolbox: A Meta-analysis of Reliability Measurement Precision

My study investigated internal consistency estimates of psychometric surveys as an operationalization of the state of measurement precision of constructs in industrial and organizational (I/O) psychology. Analyses were conducted of samples used in research articles published in the Journal of Applied Psychology between 1975 and 2010 in five year intervals (K = 934) from 480 articles yielding 1427 coefficients. Articles and their respective samples were coded for test-taker characteristics (e.g., age, gender, and ethnicity), research settings (e.g., lab and field studies), and actual tests (e.g., number of items and scale anchor points). A reliability and inter-item correlations depository was developed for I/O variables and construct groups. Personality measures had significantly lower inter-item correlations than other construct groups. Also, internal consistency estimates and reporting practices were evaluated over time, demonstrating an improvement in measurement precision and missing data.

Pelvic floor muscle training versus no treatment, or inactive control treatments, for urinary incontinence in women : a short version Cochrane systematic review with meta-analysis

Background Pelvic floor muscle training (PFMT) is a commonly used physical therapy for women with urinary incontinence (UI). Objectives To determine the effects of PFMT for women with UI in comparison to no treatment, placebo or other inactive control treatments. Search Methods Cochrane Incontinence Group Specialized Register, (searched 15 April 2013). Selection Criteria Randomized or quasi-randomized trials in women with stress, urgency or mixed UI (based on symptoms, signs, or urodynamics). Data Collection and Analysis At least two independent review authors carried out trial screening, selection, risk of bias assessment and data abstraction. Trials were subgrouped by UI diagnosis. The quality of evidence was assessed by adopting the (GRADE) approach. Results Twenty-one trials (1281 women) were included; 18 trials (1051 women) contributed data to the meta-analysis. In women with stress UI, there was high quality evidence that PFMT is associated with cure (RR 8.38; 95% CI 3.68 to 19.07) and moderate quality evidence of cure or improvement (RR 17.33; 95% CI 4.31 to 69.64). In women with any type of UI, there was also moderate quality evidence that PFMT is associated with cure (RR 5.5; 95% CI 2.87–10.52), or cure and improvement (RR 2.39; 95% CI 1.64–3.47). Conclusions The addition of seven new trials did not change the essential findings of the earlier version of this review. In this iteration, using the GRADE quality criteria strengthened the recommendations for PFMT and a wider range of secondary outcomes (also generally in favor of PFMT) were reported.

What Are Effective Program Characteristics of Self-Management Interventions in Patients With Heart Failure? : An Individual Patient Data Meta-analysis

Background To identify those characteristics of self-management interventions in patients with heart failure (HF) that are effective in influencing health-related quality of life, mortality, and hospitalizations. Methods and Results Randomized trials on self-management interventions conducted between January 1985 and June 2013 were identified and individual patient data were requested for meta-analysis. Generalized mixed effects models and Cox proportional hazard models including frailty terms were used to assess the relation between characteristics of interventions and health-related outcomes. Twenty randomized trials (5624 patients) were included. Longer intervention duration reduced mortality risk (hazard ratio 0.99, 95% confidence interval [CI] 0.97–0.999 per month increase in duration), risk of HF-related hospitalization (hazard ratio 0.98, 95% CI 0.96–0.99), and HF-related hospitalization at 6 months (risk ratio 0.96, 95% CI 0.92–0.995). Although results were not consistent across outcomes, interventions comprising standardized training of interventionists, peer contact, log keeping, or goal-setting skills appeared less effective than interventions without these characteristics. Conclusion No specific program characteristics were consistently associated with better effects of self-management interventions, but longer duration seemed to improve the effect of self-management interventions on several outcomes. Future research using factorial trial designs and process evaluations is needed to understand the working mechanism of specific program characteristics of self-management interventions in HF patients.

Peripheral brain-derived neurotrophic factor levels in alzheimer's disease and mild cognitive impairment: A comprehensive systematic review and meta-analysis

Alzheimer's disease (AD) is becoming a growing global problem, and there is an urgent need to identify reliable blood biomarkers of the risk and progression of this condition. A potential candidate is the brain-derived neurotrophic factor (BDNF), which modulates major trophic effects in the brain. However, findings are apparently inconsistent regarding peripheral blood BDNF levels in AD patients vs. healthy people. We thus performed a systematic review and meta-analysis of the studies that have examined peripheral BDNF levels in patients with AD or mild cognitive impairment (MCI) and healthy controls. We searched articles through PubMed, EMBASE, and hand searching. Over a total pool of 2061 potential articles, 26 met all inclusion criteria (including a total of 1584 AD patients, 556 MCI patients, and 1294 controls). A meta-analysis of BDNF levels between early AD and controls showed statistically significantly higher levels (SMD [95 % CI]: 0.72 [0.31, 1.13]) with no heterogeneity. AD patients with a low (<20) mini-mental state examination (MMSE) score had lower peripheral BDNF levels compared with controls (SMD [95 % CI]: -0.33 [-0.60, -0.05]). However, we found no statistically significant difference in blood (serum/plasma) BDNF levels between all AD patients and controls (standard mean difference, SMD [95 % CI]: -0.16 [-0.4, 0.07]), and there was heterogeneity among studies (P < 0.0001, I 2 = 85.8 %). There were no differences in blood BDNF levels among AD or MCI patients vs. controls by subgroup analyses according to age, sex, and drug use. In conclusion, this meta-analysis shows that peripheral blood BDNF levels seem to be increased in early AD and decreased in AD patients with low MMSE scores respectively compared with their age- and sex-matched healthy referents. At present, however, this could not be concluded from individual studies.

A systematic review and meta-analysis on the longitudinal relationship between eating pathology and depression.

OBJECTIVE: Undertake a meta-analysis to provide a quantitative synthesis of longitudinal studies that assessed the direction of effects between eating pathology and depression. A second aim was to use meta-regression to account for heterogeneity in terms of study-level effect modifiers. METHOD: A systematic review was conducted on 42 studies that assessed the longitudinal relationship between eating pathology and depression. Of these 42 studies, multilevel random-effects meta-analyses were conducted on 30 eligible studies. RESULTS: Meta-analysis results showed that eating pathology was a risk factor for depression (rm  = 0.13) and that depression was a risk factor for eating pathology (rm  = 0.16). Meta-regression analyses showed that these effects were significantly stronger for studies that operationalized eating pathology as an eating disorder diagnosis versus eating pathology symptoms, and for studies that operationalized the respective outcome measure as a categorical variable (e.g., a diagnosis of a disorder or where symptoms were "present"/"absent") versus a continuous measure. Results also showed that in relation to eating pathology type, the effect of an eating disorder diagnosis and bulimic symptoms on depression was significantly stronger for younger participants. DISCUSSION: Eating pathology and depression are concurrent risk factors for each other, suggesting that future research would benefit from identifying factors that are etiological to the development of both constructs. RESUMEN OBJETIVO: Llevar a cabo un meta-análisis para proporcionar una síntesis cuantitativa de los estudios longitudinales que evaluaron la dirección de los efectos entre la alimentación patológica y la depresión. Un segundo objetivo fue utilizar la meta-regresión para dar cuenta de la heterogeneidad en términos de modificadores del efecto a nivel de estudio. MÉTODO: Una revisión sistemática se llevó a cabo en 42 estudios que evaluaron la relación longitudinal entre la alimentación patológica y la depresión. De estos 42 estudios, se realizaron meta-análisis de multinivel de efectos aleatorios en 30 estudios elegibles. RESULTADOS: Los resultados del meta-análisis mostraron que la alimentación patológica era un factor de riesgo para depresión (rm=0.13) y que la depresión era un factor de riesgo para la alimentación patológica (rm=0.16). Los análisis de meta-regresión mostraron que estos efectos eran significativamente más fuertes para estudios que operacionalizaban la alimentación patológica como un diagnóstico de trastorno de la conducta alimentaria versus síntomas de alimentación patológica, y para los estudios que operacionalizaban la medida respectiva de resultado como una variable categórica (e.g., un diagnóstico de trastorno o cuando los síntomas estaban "presentes"/"ausentes") versus una medida continua. Los resultados mostraron que en relación al tipo de alimentación patológica, el efecto de un diagnóstico de trastorno de la conducta alimentaria y síntomas bulímicos en la depresión era significativamente más fuerte para participantes más jóvenes. DISCUSIÓN: La alimentación patológica y la depresión son factores de riesgo concurrentes uno para el otro, lo que sugiere que la investigación futura se beneficiaría de identificar factores que son etiológicos al desarrollo de ambos constructos. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016;49:439-454).