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Dietary zinc is associated with a lower incidence of depression: Findings from two Australian cohorts

Background Several animal and human studies have shown that zinc plays a role in reducing depression, but there have been no longitudinal studies in both men and women on this topic. The aim of this study was to investigate dietary zinc, and the zinc to iron ratio, as predictors of incident depression in two large longitudinal studies of mid-age and older Australians. Methods Data were self-reported, as part of the Australian Longitudinal Study on Women׳s Health (women aged 50–61 years) and Hunter Community Study (men and women aged 55–85 years). Validated food frequency questionnaires were used to assess dietary intake. Energy-adjusted zinc was ranked using quintiles and predictors of incident depression were examined using multivariate logistic regression. Results Both studies showed an inverse association between dietary zinc intake and risk of depression, even after adjusting for potential confounders. Compared to those with the lowest zinc intake those with the highest zinc intake had significantly lower odds of developing depression with a reduction of about 30–50%. There was no association between the zinc to iron ratio and developing depression in either study. Limitations Dietary assessment was carried out only at baseline and although adjustments were made for all known potential confounders, residual confounding cannot be entirely excluded. Conclusions Low dietary zinc intake is associated with a greater incidence of depression in both men and women, as shown in two prospective cohorts. Further studies into the precise role of zinc compared to other important nutrients from the diet are needed.

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Longitudinal Associations Among Bullying by Peers, Disordered Eating Behavior, and Symptoms of Depression During Adolescence.

Importance  Bullying by peers has been associated with disordered eating behavior and symptoms of depression among adolescents as both an antecedent and an outcome. Identification of the temporal pattern of associations among bullying by peers, disordered eating behavior, and depression in adolescence is needed for the optimal targeting of intervention and prevention.  Objective  To assess the concurrent and longitudinal associations among bullying by peers, disordered eating behavior, and symptoms of depression using a cascade model that controlled for within-time and across-time (ie, stability paths) associations while examining cross-lag effects.Design, Setting, and Participants  In this 5-year longitudinal cohort study, 612 participants of the McMaster Teen Study were included. This ongoing Canadian study examines the associations among bullying, mental health, and educational outcomes. Data collection began in 2008 when students were in grade 5 (10 years of age) and have since been collected annually. Data analysis was performed between August 20 and October 18, 2017.  Exposures  Bullying by peers was assessed in grades 7 to 11 using a composite measure of 5 items.Main Outcomes and Measures  Disordered eating behavior was assessed in grades 7 to 11 using the Short Screen for Eating Disorders, and depressive symptoms were assessed in grades 7 to 11 using the Behavior Assessment System for Children–Second Edition.  Results  The 612 students included in the analytic sample had a mean age (SD) of 13.03 (0.38) years in grade 7; 331 (54.1%) were girls and 392 (71.1%) were white. Bullying by peers was concurrently associated with disordered eating behavior and depressive symptoms at every time point during the 5-year period (r range [SE], 0.15-0.48 [0.04-0.08]; P < .01). Disordered eating behavior was associated longitudinally with depressive symptoms at every time point (β range [SE], 0.14-0.19 [0.06-0.08]; P < .02) and bullying by peers at 2 time points (β range [SE], 0.12-0.22 [0.06-0.07]; P < .04) in girls and boys.  Conclusions and Relevance  Bullying by peers was proximally associated with multiple psychopathologic symptoms, whereas symptoms of disordered eating behavior were a key risk factor for future depressive symptoms and bullying by peers. Interventions aimed at reducing problematic eating behavior in adolescents may attenuate the risk of future depressive symptoms and relational problems.

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Association of Apathy With Risk of Incident Dementia: A Systematic Review and Meta-analysis.

Importance  Fear of dementia is pervasive in older people with cognitive concerns. Much research is devoted to finding prognostic markers for dementia risk. Studies suggest apathy in older people may be prodromal to dementia and could be a relevant, easily measurable predictor of increased dementia risk. However, evidence is fragmented and methods vary greatly between studies.  Objective  To systematically review and quantitatively synthesize the evidence for an association between apathy in dementia-free older individuals and incident dementia.  Data Sources  Two reviewers conducted a systematic search of Medline, Embase, and PsychINFO databases.Study Selection  Inclusion criteria were (1) prospective cohort studies, (2) in general populations or memory clinic patients without dementia, (3) with clear definitions of apathy and dementia, and (4) reporting on the association between apathy and incident dementia.Data Extraction and Synthesis  PRISMA and MOOSE guidelines were followed. Data were extracted by 1 reviewer and checked by a second.  Main Outcomes and Measures  Main outcomes were pooled crude risk ratios, maximally adjusted reported hazard ratios (HR), and odds ratios (OR) using DerSimonian-Laird random effects models.Results  The mean age of the study populations ranged from 69.2 to 81.9 years (median, 71.6 years) and the percentage of women ranged from 35% to 70% (median, 53%). After screening 2031 titles and abstracts, 16 studies comprising 7365 participants were included. Apathy status was available for 7299 participants. Studies included populations with subjective cognitive concerns (n = 2), mild cognitive impairment (n = 11), cognitive impairment no dementia (n = 1), or mixed cognitive and no cognitive impairment (n = 2). Apathy was present in 1470 of 7299 participants (20.1%). Follow-up ranged from 1.2 to 5.4 years. In studies using validated apathy definitions (n = 12), the combined risk ratio of dementia for patients with apathy was 1.81 (95% CI, 1.32-2.50; I2 = 76%; n = 12), the hazard ratio was 2.39 (95% CI, 1.27-4.51; I2 = 90%; n = 7), and the odds ratio was 17.14 (95% CI, 1.91-154.0; I2 = 60%; n = 2). Subgroup analyses, meta-regression, and individual study results suggested the association between apathy and dementia weakened with increasing follow-up time, age, and cognitive impairment. Meta-regression adjusting for apathy definition and follow-up time explained 95% of heterogeneity in mild cognitive impairment.  Conclusions and Relevance  Apathy was associated with an approximately 2-fold increased risk of dementia in memory clinic patients. Moderate publication bias may have inflated some of these estimates. Apathy deserves more attention as a relevant, cheap, noninvasive, and easily measureable marker of increased risk of incident dementia with high clinical relevance, particularly because these vulnerable patients may forgo health care.

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Palmitoylethanolamide as adjunctive therapy in major depressive disorder: A double-blind, randomized and placebo-controlled trial

Palmitoylethanolamide as adjunctive therapy in major depressive disorder: A double-blind, randomized and placebo-controlled trial | Depression Research | Scoop.it

Background Experimental studies provide evidence for antidepressant effects of Palmitoylethanolamide (PEA) in animal models of depression. We aimed to evaluate the efficacy and tolerability of PEA add-on therapy in treatment of patients with major depressive disorder (MDD). Methods In a randomized double-blind, and placebo-controlled study, 58 patients with MDD (DSM-5) and Hamilton Depression Rating Scale (HAM-D) score ≥ 19 were randomized to receive either 600 mg twice daily Palmitoylethanolamide or placebo in addition to citalopram for six weeks. Patients were assessed using the HAM-D scale at baseline and weeks 2, 4, and 6. Results Fifty-four individuals completed the trial. At week 2, patients in the PEA group demonstrated significantly greater reduction in HAM-D scores compared to the placebo group (8.30 ± 2.41 vs. 5.81 ± 3.57, P = .004). The PEA group also demonstrated significantly greater improvement in depressive symptoms [F (3, 156) = 3.35, P = .021] compared to the placebo group throughout the trial period. The patients in the PEA group experienced more response rate (≥ 50% reduction in the HAM-D score) than the placebo group (100% vs. 74% respectively, P = .01) at the end of the trial. Baseline parameters and frequency of side effects were not significantly different between the two groups. Limitations The population size in this study was small and the follow-up period was relatively short. Conclusions Palmitoylethanolamide adjunctive therapy to citalopram can effectively improve symptoms of patients (predominantly male gender) with major depressive disorder. PEA showed rapid-onset antidepressant effects which need further investigation.

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3,4-Methylenedioxymethamphetamine as a Psychiatric Treatment

3,4-Methylenedioxymethamphetamine as a Psychiatric Treatment | Depression Research | Scoop.it

Within 5 years, science will likely have answered a controversial question decades in the making: can the psychoactive drug commonly known as ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) be used to treat psychiatric disorders? After positive signals in 2 small trials of MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD)1,2 and unpublished phase 2 work, MDMA investigations are moving into phase 3. Moreover, MDMA-assisted psychotherapy has obtained the breakthrough therapy designation of the US Food and Drug Administration (FDA), which is intended to expedite development and review of novel, potentially effective treatments. The nonprofit organization coordinating this research, the Multidisciplinary Association for Psychedelic Studies (MAPS), estimates that phase 3 studies enrolling at least 200 participants will be completed by 2020, with a new drug application submitted to the FDA shortly thereafter. Of importance, the phase 3 protocols have undergone FDA special protocol assessment, increasing the chances of rapid approval in the event of positive results. Thus, MDMA may be approved for prescription by 2021, necessitating consideration of several important regulatory and clinical issues. Herein, I provide an overview of MDMA-assisted psychotherapy and key associated questions from the viewpoint that these issues need to be considered by psychiatry beyond the small community of MDMA therapy advocates.

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affron®, a standardised extract from saffron (Crocus sativus L.) for the treatment of youth anxiety and depressive symptoms: A randomised, double-blind, placebo-controlled study.

affron®, a standardised extract from saffron (Crocus sativus L.) for the treatment of youth anxiety and depressive symptoms: A randomised, double-blind, placebo-controlled study. | Depression Research | Scoop.it

Background Saffron has antidepressant and anxiolytic effects in adults with mild-to-moderate depression. However, this is the first study examining its mood-related effects in teenagers. Methods In this 8-week, randomised, double-blind, placebo-controlled study, youth aged 12–16 years, with mild-to-moderate anxiety or depressive symptoms were given tablets containing placebo or a saffron extract (affron®, 14 mg b.i.d). The youth and parent versions of the Revised Child Anxiety and Depression Scale (RCADS) were used as outcome measures. Results 80 participants were enrolled and 68 completed the study. Based on youth self-reports, affron® was associated with greater improvements in overall internalising symptoms (p = 0.049), separation anxiety (p = 0.003), social phobia (p = 0.023), and depression (p = 0.016). Total internalising scores decreased by an average of 33% compared to 17% in the placebo group (p = 0.029). However, parental reports of improvements were inconsistent as mean improvements in RCADS scores were greater in the saffron group (40% vs 26%) (p = 0.026), although no other significant differences were identified. affron® was well-tolerated and there was a trend of reduced headaches in participants on the active treatment. Limitations The use of a self-report instrument, limited study duration, single treatment dose, and non-clinical sample used in this study limit the generalisability of study findings. Conclusion The administration of a standardised saffron extract (affron®) for 8 weeks improved anxiety and depressive symptoms in youth with mild-to-moderate symptoms, at least from the perspective of the adolescent. However, these beneficial effects were inconsistently corroborated by parents.

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Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized.

Objective: Pharmacotherapy to rapidly relieve suicidal ideation in depression may reduce suicide risk. Rapid reduction in suicidal thoughts after ketamine treatment has mostly been studied in patients with low levels of suicidal ideation. The authors tested the acute effect of adjunctive subanesthetic intravenous ketamine on clinically significant suicidal ideation in patients with major depressive disorder.  Method: In a randomized clinical trial, adults (N=80) with current major depressive disorder and a score ≥4 on the Scale for Suicidal Ideation (SSI), of whom 54% (N=43) were taking antidepressant medication, were randomly assigned to receive ketamine or midazolam infusion. The primary outcome measure was SSI score 24 hours after infusion (at day 1). Results: The reduction in SSI score at day 1 was 4.96 points greater for the ketamine group compared with the midazolam group (95% CI=2.33, 7.59; Cohen’s d=0.75). The proportion of responders (defined as having a reduction ≥50% in SSI score) at day 1 was 55% for the ketamine group and 30% for the midazolam group (odds ratio=2.85, 95% CI=1.14, 7.15; number needed to treat=4.0). Improvement in the Profile of Mood States depression subscale was greater at day 1 for the ketamine group compared with the midazolam group (estimate=7.65, 95% CI=1.36, 13.94), and this effect mediated 33.6% of ketamine’s effect on SSI score. Side effects were short-lived, and clinical improvement was maintained for up to 6 weeks with additional optimized standard pharmacotherapy in an uncontrolled follow-up.  Conclusions: Adjunctive ketamine demonstrated a greater reduction in clinically significant suicidal ideation in depressed patients within 24 hours compared with midazolam, partially independently of antidepressant effect. [Note too the thoughtful linked editorial in the same issue of this journal].

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Association of Obsessive-Compulsive Disorder With Objective Indicators of Educational Attainment: A Nationwide Register-Based Sibling Control Study

Importance  To our knowledge, the association of obsessive-compulsive disorder (OCD) and academic performance has not been objectively quantified.  Objective  To investigate the association of OCD with objectively measured educational outcomes in a nationwide cohort, adjusting for covariates and unmeasured factors shared between siblings.  Design, Setting, And Participants  This population-based birth cohort study included 2 115 554 individuals who were born in Sweden between January 1, 1976, and December 31, 1998, and followed up through December 31, 2013. Using the Swedish National Patient Register and previously validated International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, we identified persons with OCD; within the cohort, we identified 726 198 families with 2 or more full siblings, and identified 11 482 families with full siblings discordant for OCD. Data analyses were conducted from October 1, 2016, to September 25, 2017.  Main Outcomes and Measures  The study evaluates the following educational milestones: eligibility to access upper secondary school after compulsory education, finishing upper secondary school, starting a university degree, finishing a university degree, and finishing postgraduate education.  Results  Of the 2 115 554 individuals in the cohort, 15 120 were diagnosed with OCD (59% females). Compared with unexposed individuals, those with OCD were significantly less likely to pass all core and additional courses at the end of compulsory school (adjusted odds ratio [aOR] range, 0.35-0.60) and to access a vocational or academic program in upper secondary education (aOR, 0.47; 95% CI, 0.45-0.50 and aOR, 0.61; 95% CI, 0.58-0.63, for vocational and academic programs, respectively). People with OCD were also less likely to finish upper secondary education (aOR, 0.43; 95% CI, 0.41-0.44), start a university degree (aOR, 0.72; 95% CI, 0.69-0.75), finish a university degree (aOR, 0.59; 95% CI, 0.56-0.62), and finish postgraduate education (aOR, 0.52; 95% CI, 0.36-0.77). The results were similar in the sibling comparison models. Individuals diagnosed with OCD before age 18 years showed worse educational attainment across all educational levels compared with those diagnosed at or after age 18 years. Exclusion of patients with comorbid neuropsychiatric disorders, psychotic, anxiety, mood, substance use, and other psychiatric disorders resulted in attenuated estimates, but patients with OCD were still impaired across all educational outcomes.  Conclusions and Relevance  Obsessive-compulsive disorder, particularly when it has an early onset, is associated with a pervasive and profound decrease in educational attainment, spanning from compulsory school to postgraduate education.

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A meta-analysis of the use of probiotics to alleviate depressive symptoms

A meta-analysis of the use of probiotics to alleviate depressive symptoms | Depression Research | Scoop.it

Introduction Some preclinical and clinical studies have demonstrated the positive impact of probiotic supplementation on depressive symptoms. This paper aims to provide an updated meta-analysis on the topic. Methods Using the keywords [probiotics OR gut OR microflora OR microbiome OR bacteria OR yeast OR yoghurt OR lactobacillus OR bifidobacterium] AND [mood OR depression OR MDD OR suicide], a preliminary search on the PubMed, Ovid, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR) and Cochrane Field for Complementary Medicine database yielded 917 papers published in English between 1-Jan-1960 and 1-June-2017. Results 10 clinical trials with a total of 1349 patients were reviewed, comparing the use of probiotics to placebo controls. There was no significant difference in mood between the treatment and placebo group post-intervention as the standardized mean difference (SMD) was −0.128 (95% CI −0.261 to 0.00463, P=0.059). A separate subgroup analysis of studies conducted in healthy versus depressed individuals found significant improvements in the moods of individuals with mild to moderate depressive symptoms (SMD −0.684, 95% CI −1.296 to −0.0712, P=0.029) and non-significant effects in healthy individuals (SMD −0.0999, 95% CI −0.235 to 0.0348, P=0.146). Limitations Inter-study discrepancies with respect to probiotic dosing, bacterial strains and strain combinations limit the comparability of current clinical trials. Furthermore, majority of existing RCTs were conducted in healthy individuals, making it difficult to extrapolate the results to depressed individuals. Conclusion Probiotic supplementation has an overall insignificant effect on mood. Future studies should be conducted on more patients with clinically diagnosed depression.

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Switching the Antidepressant After Nonresponse in Adults With Major Depression: A Systematic Literature Search and Meta-Analysis

Switching the Antidepressant After Nonresponse in Adults With Major Depression: A Systematic Literature Search and Meta-Analysis | Depression Research | Scoop.it

OBJECTIVE: Nonresponders to antidepressant monotherapy during acute treatment of major depression are often switched to a new antidepressant. The objective of this meta-analysis was to compare the efficacy of switching to a new antidepressant with continuation of the first antidepressant. DATA SOURCES: PubMed, Embase, PsycINFO, and Cochrane Central Register of Controlled Trials (CENTRAL) databases and additional sources were systematically searched independently by 2 authors up to March 2015 without language limitations. With employment of a sensitivity-enhancing search strategy, generic terms for major depression, switching, and randomized trials were combined. STUDY SELECTION: Articles (3,234) were screened for trials of patients with major depression who had not responded to antidepressant monotherapy who were then randomized either to a new antidepressant or to continuation of the first antidepressant. Studies were subdivided into those not allowing for dose escalation in the continuation arm (strict analysis) and those allowing for dose escalation (broad analysis). DATA EXTRACTION: Data were extracted and risk of bias was assessed independently by 2 authors, and data were pooled using random effects models. RESULTS: Four randomized controlled trials were included in the strict analysis and 8 in the broad analysis. In both analyses, switching was not superior to continuation: the standardized mean difference in the strict analysis was -0.17 (95% CI, -0.59 to 0.26; P = .45; I(2) = 77.8%) and in the broad analysis was 0.031 (95% CI, -0.26 to 0.32; P = .836; I(2) = 85.3%). All secondary outcome analyses (response and remission rates, low risk of bias studies only, leave-one-out analysis, dropouts) supported the results. There was no indication of publication bias. CONCLUSIONS: There is a dearth of randomized controlled trials investigating switching. There is no high-level evidence that switching the antidepressant is effective when compared to simply continuing the initial antidepressant. Since there are better treatment options than switching, physicians should be cautious to switch antidepressants.

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The association between paternal and adolescent depressive symptoms: evidence from two population-based cohorts

(Available in free full text) Background Incidence of depression increases markedly around age 13 years, and nearly three-quarters of adults report that their mental health problems started in adolescence. Although maternal depression is a risk factor for adolescent depression, evidence about the association between paternal and adolescent depression is inconclusive, and many studies have methodological limitations. We aimed to assess the association between paternal and adolescent depressive symptoms in two large population-based cohort studies.  Methods We used data for two-parent families from two representative prospective cohorts in Ireland (Growing up in Ireland [GUI]) and the UK (Millennium Cohort Study [MCS]). Parental depressive symptoms were measured with the Centre for Epidemiological Studies Depression Scale in the GUI cohort when children were 9 years old, and the Kessler six-item psychological distress scale in the MCS cohort when children were 7 years old. Adolescent depressive symptoms were measured with the Short Mood and Feelings Questionnaire (SMFQ) at age 13 years in the GUI cohort and age 14 years in the MCS cohort. We analysed data using linear regression models, before and after adjustment for confounders, in both multiply imputed and complete case samples.  Findings There were 6070 families in GUI and 7768 in MCS. After all adjustments, a 1 SD (three-point) increase in paternal depressive symptoms was associated with an increase of 0·24 SMFQ points (95% CI 0·03–0·45; p=0·023) in the GUI cohort and 0·18 SMFQ points (0·01–0·36; p=0·041) in the MCS cohort. This association was independent of, and not different in magnitude to, the association between maternal and adolescent depressive symptoms (Wald test p=0·435 in the GUI cohort and 0·470 in the MCS cohort).  Interpretation  Our results show an association between depressive symptoms in fathers and depressive symptoms in their adolescent offspring. These findings support the involvement of fathers as well as mothers in early interventions to reduce the prevalence of adolescent depression, and highlight the importance of treating depression in both parents.

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More data, more answers: picking the optimal antidepressant

(Available in free full text) In an era of increasingly large datasets for health and emphasis on so-called big data analyses, key clinical questions remain unpretentiously simple. For example, do some antidepressants work better than others for depression? And are some more tolerable than others, at least as measured in dropout rates? A quick PubMed search of antidepressant meta-analyses yields more than 2000 hits, but the complexity of understanding which antidepressants are better or more tolerable than others is made particularly daunting by the fact that more than 40 antidepressants are available.  Andrea Cipriani and colleagues1 provided a novel answer to these questions originally in a paper published in The Lancet in 2009, introducing the new method of network meta-analysis to psychiatry and showing that four of the 12 then newer antidepressants were more efficacious than the rest. In that landmark study, the authors examined 117 trials with nearly 26 000 participants. 9 years later in The Lancet, Cipriani and colleagues2 report their work applying a similar method to address the same question; this time they evaluated 21 antidepressants and placebo in 522 double-blind trials with 116 477 participants. Chief among the findings are detailed new results on efficacy (8-week outcomes) and acceptability (8-week dropout rates due to all causes). The study found that all antidepressants were more efficacious than placebo, with odds ratios (ORs) ranging from 2·13 (95% credible interval [CrI] 1·89–2·41) for amitriptyline to 1·37 (1·16–1·63) for reboxetine. Additionally, the study found reduced differences between antidepressants compared with the 2009 study, with ORs (usually with broad CrIs) from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability (tolerability). More specifically, head-to-head efficacy comparisons of antidepressants disclosed seven agents (agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine) as distinctly more effective and four agents (fluoxetine, fluvoxamine, reboxetine, and trazodone) to be somewhat less effective than the other antidepressants … A key question—raised in 2009—remains, what is the implication of superiority of outcomes at 8 weeks for long-term effects, particularly functional outcomes?9 Although network meta-analysis is exemplary as a technique to combine aggregate data, such aggregation does not allow for analysis at the individual patient level and so cannot provide finer detail on who might preferentially respond or who might be more vulnerable to side-effects … An additional important facet missed by network meta-analysis involves the heterogeneity of response within major depressive disorder, identified by other statistical approaches. Using growth mixture modelling, distinct trajectories of responders (76%) and non-responders (24%) to duloxetine were identified.10 Although clinical phenotyping on the basis of traditional specifiers of melancholia, atypical symptoms, and anxiety have not been helpful in predicting treatment response,11 the integration of clinical and biological markers shows more promise. One recent study12 integrated clinical and neuroimaging markers to identify four distinct neurophysiological biotypes in more than 1000 patients with major depressive disorder on the basis of resting-state functional connectivity. These biotypes were linked to clinical dimensions of anhedonia and anxiety, and predicted response to repetitive transcranial magnetic stimulation. Ultimately, the field requires different research strategies to identify response at the level of the individual patient, not just network meta-analysis with larger sample sizes.  Nevertheless, Cipriani and colleagues have made a major contribution. This study of antidepressant outcomes identified significant differences between antidepressants that are relevant to health-care economists and policy makers, clinicians, and patients. In everyday clinical practice, medications with the highest net efficacy and acceptability ratings merit discussion with patients for use as the first treatment. The demonstration of the extent of antidepressant superiority over placebo reassures patients and health-care professionals of the efficacy of treatment despite high placebo response rates.

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A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED)

(Available in free full text) Objectives: We investigated whether a Mediterranean-style diet (MedDiet) supplemented with fish oil can improve mental health in adults suffering depression.Methods: Adults with self-reported depression were randomized to receive fortnightly food hampers and MedDiet cooking workshops for 3 months and fish oil supplements for 6 months, or attend social groups fortnightly for 3 months. Assessments at baseline, 3 and 6 months included mental health, quality of life (QoL) and dietary questionnaires, and blood samples for erythrocyte fatty acid analysis.  Results: n = 152 eligible adults aged 18–65 were recruited (n = 95 completed 3-month and n = 85 completed 6-month assessments). At 3 months, the MedDiet group had a higher MedDiet score (t = 3.95, P < 0.01), consumed more vegetables (t = 3.95, P < 0.01), fruit (t = 2.10, P = 0.04), nuts (t = 2.29, P = 0.02), legumes (t = 2.41, P = 0.02) wholegrains (t = 2.63, P = 0.01), and vegetable diversity (t = 3.27, P < 0.01); less unhealthy snacks (t = −2.10, P = 0.04) and red meat/chicken (t = −2.13, P = 0.04). The MedDiet group had greater reduction in depression (t = −2.24, P = 0.03) and improved mental health QoL scores (t = 2.10, P = 0.04) at 3 months. Improved diet and mental health were sustained at 6 months. Reduced depression was correlated with an increased MedDiet score (r = −0.298, P = 0.01), nuts (r = −0.264, P = 0.01), and vegetable diversity (r = −0.303, P = 0.01). Other mental health improvements had similar correlations, most notably for increased vegetable diversity and legumes. There were some correlations between increased omega-3, decreased omega-6 and improved mental health.  Discussion: This is one of the first randomized controlled trials to show that healthy dietary changes are achievable and, supplemented with fish oil, can improve mental health in people with depression.

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Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms

Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms | Depression Research | Scoop.it

(Available in free full text) Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed.

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Association of Efficacy of Resistance Exercise Training With Depressive Symptoms: Meta-analysis and Meta-regression Analysis of Randomized Clinical Trials.

Association of Efficacy of Resistance Exercise Training With Depressive Symptoms: Meta-analysis and Meta-regression Analysis of Randomized Clinical Trials. | Depression Research | Scoop.it

Importance  The physical benefits of resistance exercise training (RET) are well documented, but less is known regarding the association of RET with mental health outcomes. To date, no quantitative synthesis of the antidepressant effects of RET has been conducted.  Objectives  To estimate the association of efficacy of RET with depressive symptoms and determine the extent to which logical, theoretical, and/or prior empirical variables are associated with depressive symptoms and whether the association of efficacy of RET with depressive symptoms accounts for variability in the overall effect size.  Data Sources  Articles published before August 2017, located using Google Scholar, MEDLINE, PsycINFO, PubMed, and Web of Science.Study Selection  Randomized clinical trials included randomization to RET (n = 947) or a nonactive control condition (n = 930).Data Extraction and Synthesis  Hedges d effect sizes were computed and random-effects models were used for all analyses. Meta-regression was conducted to quantify the potential moderating influence of participant and trial characteristics.  Main Outcomes and Measures  Randomized clinical trials used validated measures of depressive symptoms assessed at baseline and midintervention and/or postintervention. Four primary moderators were selected a priori to provide focused research hypotheses about variation in effect size: total volume of prescribed RET, whether participants were healthy or physically or mentally ill, whether or not allocation and/or assessment were blinded, and whether or not the RET intervention resulted in a significant improvement in strength.  Results  Fifty-four effects were derived from 33 randomized clinical trials involving 1877 participants. Resistance exercise training was associated with a significant reduction in depressive symptoms with a moderate-sized mean effect ∆ of 0.66 (95% CI, 0.48-0.83; z = 7.35; P < .001). Significant heterogeneity was indicated (total Q = 216.92, df = 53; P < .001; I2 = 76.0% [95% CI, 72.7%-79.0%]), and sampling error accounted for 32.9% of observed variance. The number needed to treat was 4. Total volume of prescribed RET, participant health status, and strength improvements were not significantly associated with the antidepressant effect of RET. However, smaller reductions in depressive symptoms were derived from randomized clinical trials with blinded allocation and/or assessment.  Conclusions and Relevance  Resistance exercise training significantly reduced depressive symptoms among adults regardless of health status, total prescribed volume of RET, or significant improvements in strength. Better-quality randomized clinical trials blinding both allocation and assessment and comparing RET with other empirically supported treatments for depressive symptoms are needed.

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Deprescribing benzodiazepine receptor agonists: evidence-based clinical practice guideline.

Deprescribing benzodiazepine receptor agonists: evidence-based clinical practice guideline. | Depression Research | Scoop.it

(Available in free full text) Objective To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper and stop benzodiazepine receptor agonists (BZRAs); to focus on the highest level of evidence available and seek input from primary care professionals in the guideline development, review, and endorsement processes.  Methods The overall team comprised 8 clinicians (1 family physician, 2 psychiatrists, 1 clinical psychologist, 1 clinical pharmacologist, 2 clinical pharmacists, and 1 geriatrician) and a methodologist; members disclosed conflicts of interest. For guideline development, a systematic process was used, including the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence was generated by conducting a systematic review of BZRA deprescribing trials for insomnia, as well as performing a review of reviews of the harms of continued BZRA use and narrative syntheses of patient preferences and resource implications. This evidence and GRADE quality of evidence ratings were used to generate recommendations. The team refined guideline content and recommendations through consensus and synthesized clinical considerations to address front-line clinician questions. The draft guideline was reviewed by clinicians and stakeholders.  Recommendations We recommend that deprescribing (tapering slowly) of BZRAs be offered to elderly adults (≥ 65 years) who take BZRAs, regardless of duration of use, and suggest that deprescribing (tapering slowly) be offered to adults aged 18 to 64 who have used BZRAs for more than 4 weeks. These recommendations apply to patients who use BZRAs to treat insomnia on its own (primary insomnia) or comorbid insomnia where potential underlying comorbidities are effectively managed. This guideline does not apply to those with other sleep disorders or untreated anxiety, depression, or other physical or mental health conditions that might be causing or aggravating insomnia.  Conclusion Benzodiazepine receptor agonists are associated with harms, and therapeutic effects might be short term. Tapering BZRAs improves cessation rates compared with usual care without serious harms. Patients might be more amenable to deprescribing conversations if they understand the rationale (potential for harm), are involved in developing the tapering plan, and are offered behavioural advice. This guideline provides recommendations for making decisions about when and how to reduce and stop BZRAs. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.

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Light therapy for older patients with non-seasonal depression: A systematic review and meta-analysis

Light therapy for older patients with non-seasonal depression: A systematic review and meta-analysis | Depression Research | Scoop.it

Background Light therapy has become an increasingly common treatment for adults with depression, yet the role of light therapy for non-seasonal depression among older adults remains unclear. Objective This meta-analysis sought to evaluate the effectiveness of light therapy among older patients with non-seasonal depression. Methods We searched the Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of Science, CNKI and CBM from the inception of each database to May 2017. Two researchers conducted the literature screening, data extraction, and methodological quality assessment independently. We used the Cochrane Collaboration's bias assessment tool to evaluate the risk of bias for included studies, and Review Manager 5.2.3 Software for the meta-analysis. Results Six trials with a total of 359 patients were included, and five studies were assessed as being of low risk for bias. We evaluated the effect of light therapy on depression by the reduction of depressive symptoms (SMD = 0.45; 95% CI= [0.14, 0.75]). The subgroup analysis did not find significant moderating effects of depression with intervention intensity, light type, measuring scale or intervention duration. Limitations Most of the study samples were not representative of the larger population of adults and therefore caution should be used when interpreting the findings. Conclusions Light therapy has a positive effect on geriatric non-seasonal depression. Studies with larger sample sizes are needed to confirm the curative effect of light therapy in the future.

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Epidemiology of Adult DSM-5 Major Depressive Disorder and Its Specifiers in the United States

Importance  No US national data are available on the prevalence and correlates of DSM-5–defined major depressive disorder (MDD) or on MDD specifiers as defined in DSM-5.Objective  To present current nationally representative findings on the prevalence, correlates, psychiatric comorbidity, functioning, and treatment of DSM-5 MDD and initial information on the prevalence, severity, and treatment of DSM-5 MDD severity, anxious/distressed specifier, and mixed-features specifier, as well as cases that would have been characterized as bereavement in DSM-IV.  Design, Setting, and Participants  In-person interviews with a representative sample of US noninstitutionalized civilian adults (≥18 years) (n = 36 309) who participated in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III). Data were collected from April 2012 to June 2013 and were analyzed in 2016-2017.  Main Outcomes and Measures  Prevalence of DSM-5 MDD and the DSM-5 specifiers. Odds ratios (ORs), adjusted ORs (aORs), and 95% CIs indicated associations with demographic characteristics and other psychiatric disorders.Results  Of the 36 309 adult participants in NESARC-III, 12-month and lifetime prevalences of MDD were 10.4% and 20.6%, respectively. Odds of 12-month MDD were significantly lower in men (OR, 0.5; 95% CI, 0.46-0.55) and in African American (OR, 0.6; 95% CI, 0.54-0.68), Asian/Pacific Islander (OR, 0.6; 95% CI, 0.45-0.67), and Hispanic (OR, 0.7; 95% CI, 0.62-0.78) adults than in white adults and were higher in younger adults (age range, 18-29 years; OR, 3.0; 95% CI, 2.48-3.55) and those with low incomes ($19 999 or less; OR, 1.7; 95% CI, 1.49-2.04). Associations of MDD with psychiatric disorders ranged from an aOR of 2.1 (95% CI, 1.84-2.35) for specific phobia to an aOR of 5.7 (95% CI, 4.98-6.50) for generalized anxiety disorder. Associations of MDD with substance use disorders ranged from an aOR of 1.8 (95% CI, 1.63-2.01) for alcohol to an aOR of 3.0 (95% CI, 2.57-3.55) for any drug. Most lifetime MDD cases were moderate (39.7%) or severe (49.5%). Almost 70% with lifetime MDD had some type of treatment. Functioning among those with severe MDD was approximately 1 SD below the national mean. Among 12.9% of those with lifetime MDD, all episodes occurred just after the death of someone close and lasted less than 2 months. The anxious/distressed specifier characterized 74.6% of MDD cases, and the mixed-features specifier characterized 15.5%. Controlling for severity, both specifiers were associated with early onset, poor course and functioning, and suicidality.  Conclusions and Relevance  Among US adults, DSM-5 MDD is highly prevalent, comorbid, and disabling. While most cases received some treatment, a substantial minority did not. Much remains to be learned about the DSM-5 MDD specifiers in the general population.

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A pilot study of minocycline for the treatment of bipolar depression: Effects on cortical glutathione and oxidative stress in vivo.

A pilot study of minocycline for the treatment of bipolar depression: Effects on cortical glutathione and oxidative stress in vivo. | Depression Research | Scoop.it

Background The antibiotic minocycline appears to promote neuroprotection through antioxidant and other mechanisms that may be relevant to the pathophysiology of bipolar disorder. The present study assessed the efficacy of minocycline in bipolar depression and examined the association between minocycline treatment and brain glutathione (GSH), an essential regulator of oxidative stress. Method Twenty patients with bipolar disorder experiencing acute depressive symptoms enrolled in an 8-week, open-label trial of adjuvant minocycline. Depression was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and proton magnetic resonance spectroscopy (1H MRS) measures of cortical GSH within a voxel prescribed in the precuneus and aspects of the occipital cortex were obtained from a subset of patients (n=12) before and after treatment. Results The daily dose of minocycline at study end was 256mg (SD: 71mg). Treatment was associated with improvements in depression severity [MADRS score change: –14.6 (95% CI: –7.8 to –21.3)]. Ten patients (50%) were classified as responders based on a ≥50% reduction in MADRS score and 8 patients (40%) were classified as remitters (MADRS score ≤ 9). Higher baseline GSH levels were associated with greater improvement in MADRS score following treatment (ρ=0.51, p=0.05). Increases in GSH levels at study end were higher in non-responders than in responders (p=0.04). Limitations Small sample size, lack of a placebo group. Conclusion Minocycline may be an effective adjuvant treatment for bipolar depression, particularly in patients with high baseline GSH levels. Further research is needed to evaluate the potential of minocycline in this population.

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Antidepressants versus placebo for panic disorder in adults - Cochrane Review

Antidepressants versus placebo for panic disorder in adults - Cochrane Review | Depression Research | Scoop.it

(Available in free full text) 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; and 3. 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.

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Seasonality of depressive symptoms in women but not in men: A cross-sectional study in the UK Biobank cohort

Seasonality of depressive symptoms in women but not in men: A cross-sectional study in the UK Biobank cohort | Depression Research | Scoop.it

Background We examined whether seasonal variations in depressive symptoms occurred independently of demographic and lifestyle factors, and were related to change in day length and/or outdoor temperature. Methods In a cross-sectional analysis of >150,000 participants of the UK Biobank cohort, we used the cosinor method to assess evidence of seasonality of a total depressive symptoms score and of low mood, anhedonia, tenseness and tiredness scores in women and men. Associations of depressive symptoms with day length and mean outdoor temperature were then examined. Results Seasonality of total depressive symptom scores, anhedonia and tiredness scores was observed in women but not men, with peaks in winter. In women, increased day length was associated with reduced reporting of low mood and anhedonia, but with increased reporting of tiredness, independent of demographic and lifestyle factors. Associations with day length were not independent of the average outdoor temperature preceding assessment. Limitations This was a cross-sectional investigation – longitudinal studies of within-subject seasonal variation in mood are necessary. Outcome measures relied on self-report and measured only a subset of depressive symptoms. Conclusion This large, population-based study provides evidence of seasonal variation in depressive symptoms in women. Shorter days were associated with increased feelings of low mood and anhedonia in women. Clinicians should be aware of these population-level sex differences in seasonal mood variations in order to aid recognition and treatment of depression and subclinical depressive symptoms.

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Efficacy & safety of levomilnacipran, vilazodone & vortioxetine compared with other 2nd generation antidepressants for major depressive disorder in adults: A systematic review & network meta-analysis

Efficacy & safety of levomilnacipran, vilazodone & vortioxetine compared with other 2nd generation antidepressants for major depressive disorder in adults: A systematic review & network meta-analysis | Depression Research | Scoop.it

Background Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Levomilnacipran, vilazodone and vortioxetine are the latest therapeutic options approved for the treatment of MDD. This systematic review aims to compare the benefits and harms of vilazodone, levomilnacipran, and vortioxetine with one another and other second-generation antidepressants. Methods We searched electronic databases up to September 2017 and reviewed reference lists and pharmaceutical dossiers to detect published and unpublished studies. Two reviewers independently screened abstracts and full text articles, and rated the risk of bias of included studies. Randomized controlled trials (RCTs) and controlled observational studies including adult outpatients with MDD were eligible for inclusion. We conducted network meta-analyses on response to treatment using frequentist multivariate meta-analyses models. Placebo- and active-controlled trials were eligible for network meta-analyses. Results Twenty-four studies met our inclusion criteria. Direct comparisons were limited to vilazodone versus citalopram, and vortioxetine versus duloxetine, paroxetine, or venlafaxine XR (extended release). Results of head-to-head trials and network meta-analyses, overall, indicated similar efficacy among levomilnacipran, vilazodone, or vortioxetine and other second-generation antidepressants. Although rates of overall adverse events and discontinuation due to adverse events were similar, RCTs reported several differences in specific adverse events. For most outcomes the strength of evidence was low. Limitations Limitations are the focus of literature searches on studies published in English, possible reporting biases, and general methodological limitations of network meta-analyses. Conclusions Overall, the available evidence does not indicate greater benefits or fewer harms of levomilnacipran, vilazodone, and vortioxetine compared with other second-generation antidepressants.

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Adjunctive Bright Light Therapy for Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Trial

Adjunctive Bright Light Therapy for Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Trial | Depression Research | Scoop.it

Objective: Patients with bipolar disorder have recurrent major depression, residual mood symptoms, and limited treatment options. Building on promising pilot data, the authors conducted a 6-week randomized double-blind placebo-controlled trial to investigate the efficacy of adjunctive bright light therapy at midday for bipolar depression. The aims were to determine remission rate, depression symptom level, and rate of mood polarity switch, as well as to explore sleep quality.Method:The study enrolled depressed adults with bipolar I or II disorder who were receiving stable dosages of antimanic medication (excluding patients with hypomania or mania, mixed symptoms, or rapid cycling). Patients were randomly assigned to treatment with either 7,000-lux bright white light or 50-lux dim red placebo light (N=23 for each group). Symptoms were assessed weekly with the Structured Interview Guide for the Hamilton Depression Scale With Atypical Depression Supplement (SIGH-ADS), the Mania Rating Scale, and the Pittsburgh Sleep Quality Index. Remission was defined as having a SIGH-ADS score of 8 or less.Results: At baseline, both groups had moderate depression and no hypomanic or manic symptoms. Compared with the placebo light group, the group treated with bright white light experienced a significantly higher remission rate (68.2% compared with 22.2%; adjusted odds ratio=12.6) at weeks 4–6 and significantly lower depression scores (9.2 [SD=6.6] compared with 14.9 [SD=9.2]; adjusted β=–5.91) at the endpoint visit. No mood polarity switches were observed. Sleep quality improved in both groups and did not differ significantly between them.  Conclusions:The data from this study provide robust evidence that supports the efficacy of midday bright light therapy for bipolar depression.

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The effect of paternal depression on depressive symptoms in adolescent offspring

The effect of paternal depression on depressive symptoms in adolescent offspring | Depression Research | Scoop.it

(Free full text available) Almost one in ten men will experience depression at some time in their life. Although there is evidence that partnered (and particularly married) men are at lower risk of depression than are the general male population,1 rates of depression among fathers are difficult to estimate on the basis of existing evidence.2 Fathers might not be exposed to the same risk factors for depression as mothers, but they do experience a range of biopsychosocial stressors that might affect their mental health and also have indirect effects on their partners, their children, or both.  Regardless of prevalence or risk, there is now an increasing awareness of the role that paternal depression can have in child development and later psychosocial outcomes.4, 5, 6 That being said, high quality evidence to support the development of effective policy and intervention remains scarce. The effect of perinatal paternal depression on early childhood was shown by research with longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK. Children (n=6449) whose fathers were depressed during the antenatal or postnatal periods had higher risk of emotional and behavioural problems than did those whose fathers did not have depression, when they were assessed at age 3·5 and 7 years.6 Similarly, in different samples of Australian 5–6-year-olds (n=4253) and 8–9-year-olds (n=4196), childhood social and emotional wellbeing was negatively associated with paternal psychological distress (as well as mental health problems among mothers and grandparents).7 A Finnish study of 1247 pre-adolescents found an association between paternal postnatal distress and internalising behaviour problems among their children at age 12 years.  In this issue of The Lancet Psychiatry, Gemma Lewis and colleagues9 provide evidence that associations between paternal mental health and child outcomes persist and affect adolescents, as well as younger children.8 Adolescents from the Millennium Cohort Study (MCS; n=7768) and Growing Up in Ireland (GUI; n=6070) were assessed at age 13–14 years. After adjusting for child emotional symptoms, paternal depression symptoms were significantly associated with symptoms of depression in adolescents, as noted by an increase in Short Mood and Feelings Questionnaire score (GUI 0·24 points, 95% CI 0·03–0·45, p=0·023; MCS 0·18, 0·01–0·36, p=0·041). This study explores the clinical significance of the findings, reporting an increase of 0·03–0·04 of an SD in adolescent depression scores for each 1 SD increase in paternal depressive symptoms. This association was of a similar magnitude to that between maternal depressive symptoms and adolescent depression scores.

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

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

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

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Patients’ Accounts of Increased “Connectedness” and “Acceptance” After Psilocybin for Treatment-Resistant Depression

Objective: To identify patients’ perceptions of the value of psilocybin as a treatment for depression. Method: Twenty patients enrolled in an open-label trial of psilocybin for treatment-resistant depression participated in a semistructured interview at 6-month follow-up. Thematic analysis was used to identify patients’ experiences of the treatment and how it compared with previous treatments. Results: Two main change processes were identified in relation to the treatment. The first concerned change from disconnection (from self, others, and world) to connection, and the second concerned change from avoidance (of emotion) to acceptance. A third theme concerned comparison between psilocybin and conventional treatments. Patients reported that medications and some short-term talking therapies tended to reinforce their sense of disconnection and avoidance, whereas treatment with psilocybin encouraged connection and acceptance. Conclusions: These results suggest that psilocybin treatment for depression may work via paradigmatically novel means, antithetical to antidepressant medications, and some short-term talking therapies.

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