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Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics?

Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics? | Depression Research | Scoop.it
Patients who recover from an acute episode of psychosis are frequently prescribed prophylactic antipsychotics for many years, especially if they are diagnosed as having schizophrenia. However, there is a dearth of evidence concerning the long-term effectiveness of this practice, and growing concern over the cumulative effects of antipsychotics on physical health and brain structure. Although controversy remains concerning some of the data, the wise psychiatrist should regularly review the benefit to each patient of continuing prophylactic antipsychotics against the risk of side-effects and loss of effectiveness through the development of supersensitivity of the dopamine D2 receptor. Psychiatrists should work with their patients to slowly reduce the antipsychotic to the lowest dose that prevents the return of distressing symptoms. Up to 40% of those whose psychosis remits after a first episode should be able to achieve a good outcome in the long term either with no antipsychotic medication or with a very low dose.
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Canadian 2016 clinical guidelines on alternative medical treatments for adult depression

(Available in free full text) Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals.  Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. “Complementary and Alternative Medicine Treatments” is the fifth of six sections of the 2016 guidelines.  Results: Evidence-informed responses were developed for 12 questions for 2 broad categories of complementary and alternative medicine (CAM) interventions: 1) physical and meditative treatments (light therapy, sleep deprivation, exercise, yoga, and acupuncture) and 2) natural health products (St. John’s wort, omega-3 fatty acids; S-adenosyl-L-methionine [SAM-e], dehydroepiandrosterone, folate, Crocus sativus, and others). Recommendations were based on available data on efficacy, tolerability, and safety.  Conclusions: For MDD of mild to moderate severity, exercise, light therapy, St. John’s wort, omega-3 fatty acids, SAM-e, and yoga are recommended as first- or second-line treatments. Adjunctive exercise and adjunctive St. John’s wort are second-line recommendations for moderate to severe MDD. Other physical treatments and natural health products have less evidence but may be considered as third-line treatments. CAM treatments are generally well tolerated. Caveats include methodological limitations of studies and paucity of data on long-term outcomes and drug interactions.

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A sham-controlled randomized trial of adjunctive light therapy for non-seasonal depression

A sham-controlled randomized trial of adjunctive light therapy for non-seasonal depression | Depression Research | Scoop.it

Background The aim of the study was to examine the efficacy and safety of morning bright light therapy (BLT) in the treatment of patients with a current major depressive episode (MDE) in bipolar and unipolar disorder without a seasonal pattern. It was a randomized, sham-controlled trial. Methods Adults, ages 18–70 years were randomized to treatment either with BLT or a sham negative ion generator (as a placebo control). The subjects were required to be on a stable and therapeutic dose of psychotropic medication for at least 4 weeks prior to enrollment and their treatment had to be insufficiently effective. Their clinical state was monitored at the baseline and at the end of treatment. The Hamilton Depression Rating Scale-21 items (HDRS-21), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI-II), Clinical Global Impression-Severity (CGI-S) and Patient Global Impression (PGI) were used. The results were analyzed with an intention-to-treat (ITT) analysis. Results Ninety-five patients were enrolled (50 diagnosed with bipolar disorder and 45 with unipolar depression). Fifty-two patients were randomized to treatment with BLT and forty-three were in the placebo group (ITT population). Eighty-three subjects completed the study. There were 12 dropouts (5 in the light group and 7 in the placebo group). After 14 days of treatment, a significant improvement was found in all groups (p<0.001). The subjects treated with BLT did not significantly differ in terms of improvement in HDRS-21 scores at the endpoint when compared to patients treated with placebo (p=0.2). However, further analysis demonstrated significantly higher response (50% v. 27.9%, p=0.02) and remission rates (28.8% v. 11.6%, p=0.04) among patients treated with morning BLT when compared to placebo group. It should be noted that in the population of drug-resistant patients, BLT was more efficacious than placebo. There were no statistically significant differences between unipolar and bipolar disorders (p=0.4). Conclusion Although overall improvement in HDRS-21 scores were not superior in the BLT group, both response and remission rates were significantly higher among patients treated with BLT relative to those receiving the sham intervention. BLT was also more efficacious than placebo in the population of patients with drug-resistant depression. Further studies to define the subpopulation of patients with non-seasonal depression who may benefit the most from BLT are needed.

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Whole-Body Hyperthermia for Treating Major Depressive Disorder

Whole-Body Hyperthermia for Treating Major Depressive Disorder | Depression Research | Scoop.it

Importance  Limitations of current antidepressants highlight the need to identify novel treatments for major depressive disorder. A prior open trial found that a single session of whole-body hyperthermia (WBH) reduced depressive symptoms; however, the lack of a placebo control raises the possibility that the observed antidepressant effects resulted not from hyperthermia per se, but from nonspecific aspects of the intervention.Objective  To test whether WBH has specific antidepressant effects when compared with a sham condition and to evaluate the persistence of the antidepressant effects of a single treatment.Design, Setting, and Participants  A 6-week, randomized, double-blind study conducted between February 2013 and May 2015 at a university-based medical center comparing WBH with a sham condition. All research staff conducting screening and outcome procedures were blinded to randomization status. Of 338 individuals screened, 34 were randomized, 30 received a study intervention, and 29 provided at least 1 postintervention assessment and were included in a modified intent-to-treat efficacy analysis. Participants were medically healthy, aged 18 to 65 years, met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score of 16 or greater.Interventions  A single session of active WBH vs a sham condition matched for length of WBH that mimicked all aspects of WBH except intense heat.Main Outcomes and Measures  Between-group differences in postintervention Hamilton Depression Rating Scale scores.  Results  The mean (SD) age was 36.7 (15.2) years in the WBH group and 41.47 (12.54) years in the sham group. Immediately following the intervention, 10 participants (71.4%) randomized to sham treatment believed they had received WBH compared with 15 (93.8%) randomized to WBH. When compared with the sham group, the active WBH group showed significantly reduced Hamilton Depression Rating Scale scores across the 6-week postintervention study period (WBH vs sham; week 1: −6.53, 95% CI, −9.90 to −3.16, P < .001; week 2: −6.35, 95% CI, −9.95 to −2.74, P = .001; week 4: −4.50, 95% CI, −8.17 to −0.84, P = .02; and week 6: −4.27, 95% CI, −7.94 to −0.61, P = .02). These outcomes remained significant after evaluating potential moderating effects of between-group differences in baseline expectancy scores. Adverse events in both groups were generally mild.  Conclusions and Relevance  Whole-body hyperthermia holds promise as a safe, rapid-acting, antidepressant modality with a prolonged therapeutic benefit. 

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

Statins for the treatment of depression: A meta-analysis of randomized, double-blind, placebo-controlled trials | Depression Research | Scoop.it

Abstract 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&lt;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.

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Tea consumption is inversely associated with depressive symptoms in the elderly: A cross-sectional study in eastern China

Tea consumption is inversely associated with depressive symptoms in the elderly: A cross-sectional study in eastern China | Depression Research | Scoop.it

Abstract Background Epidemiological studies suggest that higher tea consumption was associated with lower risk of depressive symptoms, but this has not been found consistently. Moreover, the effect of different types of tea on depressive symptoms needs to be further explored. This study aimed to examine the association between tea consumption and depressive symptoms in Chinese elderly. Methods We analyzed the baseline data from Zhejiang Major Public Health Surveillance Program including 9371 participants. Depressive symptoms was assessed through the application of Patient Health Questionnaire-9 scale (PHQ-9). Logistic regression models, controlled for an extensive range of potential confounders, were generated to evaluate the association between tea consumption and risk of depressive symptoms. Results The black tea drinkers had a significantly decreased risk of depressive symptoms (p<0.01), whereas no association was found in green tea drinkers. Compared with non-drinkers, the adjusted ORs (95% CIs) were 0.48 (0.23, 0.99) and 0.35 (0.17, 0.72) for participants consuming <3 cups and ≥3 cups of black tea per day, respectively (P for trend: <0.01). A linear association between concentration of black tea and depressive symptoms was also confirmed in our study. Limitations Cross-sectional data could not make a causation conclusion, and the observed association in our study could not be ascribed to any specific component in tea. Conclusions Our results indicated that higher black tea consumption was associated with a lower prevalence of depressive symptoms in the elderly.

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The prevalence and predictors of obstructive sleep apnea in major depressive disorder, bipolar disorder and schizophrenia: A systematic review and meta-analysis

The prevalence and predictors of obstructive sleep apnea in major depressive disorder, bipolar disorder and schizophrenia: A systematic review and meta-analysis | Depression Research | Scoop.it

Background Obstructive sleep apnea (OSA) is a health hazard since it is associated with neurocognitive dysfunction and cardio-metabolic diseases. The prevalence of OSA among people with serious mental illness (SMI) is unclear. Method We searched major electronic databases from inception till 06/2015. Articles were included that reported the prevalence of OSA determined by polysomnography (PSG) or an apnea-hypopnea index (AHI) > or = 5 events/hr, in people with major depressive disorder (MDD), bipolar disorder (BD) or schizophrenia. A random effects meta-analysis calculating the pooled prevalence of OSA and meta-regression of potential moderators were performed. Results Twelve articles were included representing 570,121 participants with SMI (mean age=38.3 years (SD=7.5)), 45.8% male (range=32–80.4) and mean body mass index (BMI) 25.9 (SD=3.7). The prevalence of OSA in SMI in clinical studies was 25.7% (95% CI 13.9 to 42.4%, n=1,535). Higher frequencies of OSA were seen in MDD (36.3%, 19.4–57.4%, n=525) than in BD (24.5%, 95% CI 10.6–47.1, n=681) and schizophrenia (15.4%, 95% CI 5.3–37.1%, n=329). The prevalence of OSA in 568,586 people with SMI from population cohort studies was 10.7% (95% CI 2.4–37.0%) and 19.8% (95% CI 2.5–70.0%) in 358,853 people with MDD. Increasing age (β=0.063, 95% CI 0.0005–0.126, p=0.04, N=10) and BMI predicted increased prevalence of OSA (β=0.1642, 95% CI 0.004–0.3701, p=0.04, N=9). Conclusion People with SMI (particularly MDD) have a high prevalence of OSA. Screening for and interventions to manage OSA in SMI including those focused on reducing BMI are warranted.

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Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression

Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression | Depression Research | Scoop.it

Background Trials evaluating efficacy of omega-3 highly unsaturated fatty acids (HUFAs) in major depressive disorder report discrepant findings.  Aims To establish the reasons underlying inconsistent findings among randomised controlled trials (RCTs) of omega-3 HUFAs for depression and to assess implications for further trials.  Method A systematic bibliographic search of double-blind RCTs was conducted between January 1980 and July 2014 and an exploratory hypothesis-testing meta-analysis performed in 35 RCTs including 6665 participants receiving omega-3 HUFAs and 4373 participants receiving placebo.  Results Among participants with diagnosed depression, eicosapentaenoic acid (EPA)-predominant formulations (>50% EPA) demonstrated clinical benefits compared with placebo (Hedge's G = 0.61, P < 0.001) whereas docosahexaenoic acid (DHA)-predominant formulations (>50% DHA) did not. EPA failed to prevent depressive symptoms among populations not diagnosed for depression.  Conclusions Further RCTs should be conducted on study populations with diagnosed or clinically significant depression of adequate duration using EPA-predominant omega-3 HUFA formulations.

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The Effect of Concomitant Treatment With SSRIs and Statins: A Population-Based Study

OBJECTIVE: Both preclinical studies and clinical trials have indicated that the combination of a selective serotonin reuptake inhibitor (SSRI) and a statin may have superior antidepressant effects compared with SSRI treatment alone. The authors sought to assess whether this beneficial effect can be generalized to a more heterogeneous population of SSRI users. METHOD: In a nationwide cohort study that included all incident SSRI users in Denmark between 1997 and 2012, the authors compared people who had periods of concomitant use of SSRIs and statins with people who had periods of SSRI treatment alone. Outcomes included the rates of psychiatric hospital contacts (any cause), psychiatric hospital contacts due to depression, suicidal behavior, and all-cause mortality. Using Cox regression and competing risk analysis, the authors calculated crude and adjusted hazard ratios for these outcomes. RESULTS: The authors identified 872,216 incident SSRI users, of whom 113,108 (13.0%) used a statin concomitantly. Compared with SSRI treatment alone, the combined use of an SSRI and a statin was associated with a significantly lower risk for both psychiatric hospital contacts (adjusted hazard ratio=0.75 (95% CI=0.69, 0.82) and psychiatric hospital contacts due to depression (adjusted hazard ratio=0.64, 95% CI=0.55, 0.75). Compared with SSRI treatment alone, the concomitant use of SSRIs and statins was not associated with significant increases in all-cause mortality (adjusted hazard ratio=1.04, 95% CI=0.96, 1.12) or suicidal behavior (adjusted hazard ratio=0.85, 95% CI=0.61, 1.18). CONCLUSIONS: In a large naturalistic cohort, concomitant treatment with SSRIs and statins resulted in robust advantages compared with SSRIs alone.

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Rates and predictors of remission, recurrence and conversion to bipolar disorder after the first lifetime episode of depression – a prospective 5-year follow-up study

Rates and predictors of remission, recurrence and conversion to bipolar disorder after the first lifetime episode of depression – a prospective 5-year follow-up study | Depression Research | Scoop.it

Background In depression, non-remission, recurrence of depressive episodes after remission and conversion to bipolar disorder are crucial determinants of poor outcome. The present study aimed to determine the cumulative incidences and clinical predictors of these long-term outcomes after the first lifetime episode of depression. Method A total of 301 in- or out-patients aged 18–70 years with a validated diagnosis of a single depressive episode were assessed from 2005 to 2007. At 5 years of follow-up, 262 patients were reassessed by means of the life chart method and diagnostic interviews from 2011 to 2013. Cumulative incidences and the influence of clinical variables on the rates of remission, recurrence and conversion to bipolar disorder, respectively, were estimated by survival analysis techniques. Results Within 5 years, 83.3% obtained remission, 31.5% experienced recurrence of depression and 8.6% converted to bipolar disorder (6.3% within the first 2 years). Non-remission increased with younger age, co-morbid anxiety and suicidal ideations. Recurrence increased with severity and treatment resistance of the first depression, and conversion to bipolar disorder with treatment resistance, a family history of affective disorder and co-morbid alcohol or drug abuse. Conclusions The identified clinical characteristics of the first lifetime episode of depression should guide patients and clinicians for long-term individualized tailored treatment.

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International Journal of Bipolar Disorders

International Journal of Bipolar Disorders | Depression Research | Scoop.it

(Available in free full text) Background: Bipolar disorder refers to a group of chronic psychiatric disorders of mood and energy levels. While dramatic psychiatric symptoms dominate the acute phase of the diseases, the chronic course is often determined by an increasing burden of co-occurring medical conditions. High rates of diabetes mellitus in patients with bipolar disorder are particularly striking, yet unexplained. Treatment and lifestyle factors could play a significant role, and some studies also suggest shared pathophysiology and risk factors.  Objective: In this systematic literature review, we explored data around the relationship between bipolar disorder and diabetes mellitus in recently published population-based cohort studies with special focus on the elderly.  Methods: A systematic search in the PubMed database for the combined terms “bipolar disorder” AND “elderly” AND “diabetes” in papers published between January 2009 and December 2015 revealed 117 publications; 7 studies were large cohort studies, and therefore, were included in our review.  Results: We found that age- and gender- adjusted risk for diabetes mellitus was increased in patients with bipolar disorder and vice versa (odds ratio range between 1.7 and 3.2).  Discussion: Our results in large population-based cohort studies are consistent with the results of smaller studies and chart reviews. Even though it is likely that heterogeneous risk factors may play a role in diabetes mellitus and in bipolar disorder, growing evidence from cell culture experiments and animal studies suggests shared disease mechanisms. Furthermore, disease-modifying effects of bipolar disorder and diabetes mellitus on each other appear to be substantial, impacting both treatment response and outcomes.  Conclusions: The risk of diabetes mellitus in patients with bipolar disorder is increased. Our findings add to the growing literature on this topic. Increasing evidence for shared disease mechanisms suggests new disease models that could explain the results of our study. A better understanding of the complex relationship between bipolar disorder and diabetes mellitus could lead to novel therapeutic approaches and improved outcomes.

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Hypothyroidism risk compared among nine common bipolar disorder therapies in a large US cohort

Hypothyroidism risk compared among nine common bipolar disorder therapies in a large US cohort | Depression Research | Scoop.it

(Available in free full text) Objectives Thyroid abnormalities in patients with bipolar disorder (BD) have been linked to lithium treatment for decades, yet other drugs have been less well studied. Our objective was to compare hypothyroidism risk for lithium versus the anticonvulsants and second-generation antipsychotics commonly prescribed for BD. Methods Administrative claims data on 24,574 patients with BD were analyzed with competing risk survival analysis. Inclusion criteria were (i) one year of no prior hypothyroid diagnosis nor BD drug treatment, (ii) followed by at least one thyroid test during BD monotherapy on lithium carbonate, mood-stabilizing anticonvulsants (lamotrigine, valproate, oxcarbazepine, or carbamazepine) or antipsychotics (aripiprazole, olanzapine, risperidone, or quetiapine). The outcome was cumulative incidence of hypothyroidism per drug, in the presence of the competing risk of ending monotherapy, adjusted for age, sex, physician visits, and thyroid tests. Results Adjusting for covariates, the four-year cumulative risk of hypothyroidism for lithium (8.8%) was 1.39-fold that of the lowest risk therapy, oxcarbazepine (6.3%). Lithium was non-statistically significantly different from quetiapine. While lithium conferred a higher risk when compared to all other treatments combined as a group, hypothyroidism risk error bars overlapped for all drugs. Treatment (p = 3.86e-3), age (p = 6.91e-10), sex (p = 3.93e-7), and thyroid testing (p = 2.79e-87) affected risk. Patients taking lithium were tested for hypothyroidism 2.26–3.05 times more frequently than those on other treatments. Conclusions Thyroid abnormalities occur frequently in patients with BD regardless of treatment. Therefore, patients should be regularly tested for clinical or subclinical thyroid abnormalities on all therapies and treated as indicated to prevent adverse effects of hormone imbalances on mood.

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Meta-analysis of erythrocyte polyunsaturated fatty acid biostatus in bipolar disorder

Meta-analysis of erythrocyte polyunsaturated fatty acid biostatus in bipolar disorder | Depression Research | Scoop.it

Objectives Dietary deficiency in polyunsaturated fatty acids (PUFAs), including the omega-3 fatty acids eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), and excesses in omega-6 fatty acids, including linoleic acid (LA; 18:2n-6) and arachidonic acid (AA; 20:4n-6), may be associated with the pathophysiology of bipolar disorder. In an effort to provide clarification regarding the relationship between PUFA biostatus and bipolar disorder, this meta-analysis investigated studies comparing erythrocyte (red blood cell) membrane PUFA composition in patients with bipolar disorder and healthy controls. Methods A meta-analysis was performed on case–control studies comparing erythrocyte PUFA (EPA, DHA, LA and AA) levels in patients with bipolar I disorder and healthy controls. Standardized effect sizes were calculated and combined using a random effects model. Results Six eligible case-control studies comprising n = 118 bipolar I patients and n = 147 healthy controls were included in the analysis. Compared with healthy controls, patients with bipolar I disorder exhibited robust erythrocyte DHA deficits (p = 0.0008) and there was a trend for lower EPA (p = 0.086). There were no significant differences in LA (p = 0.42) or AA (p = 0.64). Conclusions Bipolar I disorder is associated with robust erythrocyte DHA deficits. These findings add to a growing body of evidence implicating omega-3 PUFA deficiency in the pathophysiology of bipolar disorder.

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Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis

Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis | Depression Research | Scoop.it

(Available in free full text) Inflammatory cytokines are commonly elevated in acute depression and are associated with resistance to monoaminergic treatment. To examine the potential role of cytokines in the pathogenesis and treatment of depression, we carried out a systematic review and meta-analysis of antidepressant activity of anti-cytokine treatment using clinical trials of chronic inflammatory conditions where depressive symptoms were measured as a secondary outcome. Systematic search of the PubMed, EMBASE, PsycINFO and Cochrane databases, search of reference lists and conference abstracts, followed by study selection process yielded 20 clinical trials. Random effect meta-analysis of seven randomised controlled trials (RCTs) involving 2370 participants showed a significant antidepressant effect of anti-cytokine treatment compared with placebo (standardised mean difference (SMD)=0.40, 95% confidence interval (CI), 0.22-0.59). Anti-tumour necrosis factor drugs were most commonly studied (five RCTs); SMD=0.33 (95% CI; 0.06-0.60). Separate meta-analyses of two RCTs of adjunctive treatment with anti-cytokine therapy and eight non-randomised and/or non-placebo studies yielded similar small-to-medium effect estimates favouring anti-cytokine therapy; SMD=0.19 (95% CI, 0.00-0.37) and 0.51 (95% CI, 0.34-0.67), respectively. Adalimumab, etanercept, infliximab and tocilizumab all showed statistically significant improvements in depressive symptoms. Meta-regression exploring predictors of response found that the antidepressant effect was associated with baseline symptom severity (P=0.018) but not with improvement in primary physical illness, sex, age or study duration. The findings indicate a potentially causal role for cytokines in depression and that cytokine modulators may be novel drugs for depression in chronically inflamed subjects. The field now requires RCTs of cytokine modulators using depression as the primary outcome in subjects with high inflammation who are free of other physical illnesses. [Note: "About a third of patients who are resistant to antidepressants show evidence of inflammation,” adds Dr Khandaker. “So, anti-inflammatory treatments could be relevant for a large number of people who suffer from depression.]

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A meta-analysis on the efficacy and safety of St John's wort extra

(Available in free full text) Objective: The aim of the study was to investigate the efficacy and safety of St John’s wort extract and selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression.  Methods: Databases were searched for studies comparing efficacy and/or safety of St John’s wort extract with SSRIs in depression from 1966 to April 2015. Stata software was used for statistical analysis.  Results: Twenty-seven studies met the study entry criteria. A total of 3,126 patients with depression were included. St John’s wort extract did not differ from SSRIs in clinical response, remission, and mean reduction in Hamilton Rating Scale for Depression score. St John’s wort extract had a significantly lower rate of adverse events compared to SSRIs (summary relative risk: 0.77; 95% confidence interval: 0.70, 0.84, P=0.00) and had fewer withdrawals due to adverse events. St John’s wort extract had superior safety in the management of patients with depression.  Conclusion: Both St John’s wort extract and SSRIs are effective in treating mild-to-moderate depression. St John’s wort extract is safer than SSRIs.

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Daylight savings time transitions and the incidence rate of unipolar depressive disorders

BACKGROUND: Daylight savings time transitions affect approximately 1.6 billion people worldwide. Prior studies have documented associations between daylight savings time transitions and adverse health outcomes, but it remains unknown whether they also cause an increase in the incidence rate of depressive episodes. This seems likely because daylight savings time transitions affect circadian rhythms, which are implicated in the etiology of depressive disorder. Therefore, we investigated the effects of daylight savings time transitions on the incidence rate of unipolar depressive episodes. METHODS: Using time series intervention analysis of nationwide data from the Danish Psychiatric Central Research Register from 1995 to 2012 we compared the observed trend in the incidence rate of hospital contacts for unipolar depressive episodes after the transitions to and from summer time to the predicted trend in the incidence rate. RESULTS: The analyses were based on 185.419 hospital contacts for unipolar depression and showed that the transition from summer time to standard time were associated with an 11% increase (95% CI: 7%, 15%) in the incidence rate of unipolar depressive episodes that dissipated over approximately 10 weeks. The transition from standard time to summer time was not associated with a parallel change in the incidence rate of unipolar depressive episodes. CONCLUSION: This study shows that the transition from summer time to standard time was associated with an increase in the incidence rate of unipolar depressive episodes. Distress associated with the sudden advancement of sunset, marking the coming of a long period of short days, may explain this finding.

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Association of Hormonal Contraception With Depression

Association of Hormonal Contraception With Depression | Depression Research | Scoop.it

(Available in free full text) Importance  Millions of women worldwide use hormonal contraception. Despite the clinical evidence of an influence of hormonal contraception on some women’s mood, associations between the use of hormonal contraception and mood disturbances remain inadequately addressed.  Objective  To investigate whether the use of hormonal contraception is positively associated with subsequent use of antidepressants and a diagnosis of depression at a psychiatric hospital.  Design, Setting, and Participants  This nationwide prospective cohort study combined data from the National Prescription Register and the Psychiatric Central Research Register in Denmark. All women and adolescents aged 15 to 34 years who were living in Denmark were followed up from January 1, 2000, to December 2013, if they had no prior depression diagnosis, redeemed prescription for antidepressants, other major psychiatric diagnosis, cancer, venous thrombosis, or infertility treatment. Data were collected from January 1, 1995, to December 31, 2013, and analyzed from January 1, 2015, through April 1, 2016.Exposures  Use of different types of hormonal contraception.  Main Outcomes and Measures  With time-varying covariates, adjusted incidence rate ratios (RRs) were calculated for first use of an antidepressant and first diagnosis of depression at a psychiatric hospital.  Results  A total of 1 061 997 women (mean [SD] age, 24.4 [0.001] years; mean [SD] follow-up, 6.4 [0.004] years) were included in the analysis. Compared with nonusers, users of combined oral contraceptives had an RR of first use of an antidepressant of 1.23 (95% CI, 1.22-1.25). Users of progestogen-only pills had an RR for first use of an antidepressant of 1.34 (95% CI, 1.27-1.40); users of a patch (norgestrolmin), 2.0 (95% CI, 1.76-2.18); users of a vaginal ring (etonogestrel), 1.6 (95% CI, 1.55-1.69); and users of a levonorgestrel intrauterine system, 1.4 (95% CI, 1.31-1.42). For depression diagnoses, similar or slightly lower estimates were found. The relative risks generally decreased with increasing age. Adolescents (age range, 15-19 years) using combined oral contraceptives had an RR of a first use of an antidepressant of 1.8 (95% CI, 1.75-1.84) and those using progestin-only pills, 2.2 (95% CI, 1.99-2.52). Six months after starting use of hormonal contraceptives, the RR of antidepressant use peaked at 1.4 (95% CI, 1.34-1.46). When the reference group was changed to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7 (95% CI, 1.66-1.71).  Conclusions and Relevance  Use of hormonal contraception, especially among adolescents, was associated with subsequent use of antidepressants and a first diagnosis of depression, suggesting depression as a potential adverse effect of hormonal contraceptive use. [And see Guardian commentary at https://www.theguardian.com/commentisfree/2016/oct/03/pill-linked-depression-doctors-hormonal-contraceptives?CMP=fb_gu].

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Exercise as a treatment for depression: A meta-analysis adjusting for publication bias

Exercise as a treatment for depression: A meta-analysis adjusting for publication bias | Depression Research | Scoop.it

The effects of exercise on depression have been a source of contentious debate. Meta-analyses have demonstrated a range of effect sizes. Both inclusion criteria and heterogeneity may influence the effect sizes reported. The extent and influence of publication bias is also unknown. Randomized controlled trials (RCTs) were identified from a recent Cochrane review and searches of major electronic databases from 01/2013 to 08/2015. We included RCTs of exercise interventions in people with depression (including those with a diagnosis of major depressive disorder (MDD) or ratings on depressive symptoms), comparing exercise versus control conditions. A random effects meta-analysis calculating the standardized mean difference (SMD, 95% confidence interval; CI), meta-regressions, trim and fill and fail-safe n analyses were conducted. Twenty-five RCTs were included comparing exercise versus control comparison groups, including 9 examining participants with MDD. Overall, exercise had a large and significant effect on depression (SMD adjusted for publication bias = 1.11 (95% CI 0.79–1.43)) with a fail-safe number of 1057. Most adjusted analyses suggested publication bias led to an underestimated SMD. Larger effects were found for interventions in MDD, utilising aerobic exercise, at moderate and vigorous intensities, in a supervised and unsupervised format. In MDD, larger effects were found for moderate intensity, aerobic exercise, and interventions supervised by exercise professionals. Exercise has a large and significant antidepressant effect in people with depression (including MDD). Previous meta-analyses may have underestimated the benefits of exercise due to publication bias. Our data strongly support the claim that exercise is an evidence-based treatment for depression.

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Light therapy in the treatment of patients with bipolar depression: A meta-analytic study

Light therapy in the treatment of patients with bipolar depression: A meta-analytic study | Depression Research | Scoop.it

Light therapy (LT) has been widely used in the treatment of seasonal affective disorder. Recently some evidence indicated that LT may play a role in bipolar depression, either as monotherapy or in combination with total sleep deprivation (TSD). However, the studies examining the treatment effect of LT in bipolar depression resulted in inconsistent findings. To clarify the role of LT in the disorder, we conducted a meta-analysis to compare the efficacy of LT in the treatment of bipolar depression. The results of individual studies were synthesized by a random effects model. Nine studies including 489 patients with bipolar depression were included in this current meta-analysis. We found that disease severity was significantly decreased after LT, in both with and without TSD, and with concomitant medication (p&lt;0.001). Augmentation treatment with LT significantly decreased disease severity compared to treatment without LT (p=0.024). Our results highlight the significant efficacy of LT, either as monotherapy or in combination with TSD, in the treatment of bipolar depression. However, the detailed mechanism of LT still remains elusive. Further well-designed controlled trials are required to investigate the optimal intensity and frequency of LT in the treatment of bipolar depression.

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Prevalence of ADHD symptoms across clinical stages of major depressive disorder

Prevalence of ADHD symptoms across clinical stages of major depressive disorder | Depression Research | Scoop.it

Background Depression and ADHD often co-occur in clinical samples. Depression severity may be linked to ADHD symptomatology. We therefore assessed ADHD symptoms across clinical stages of major depressive disorder (MDD). Methods We used 4-year follow-up data of the Netherlands Study of Depression and Anxiety (September 2008 until April 2011), including healthy controls, groups with remitted and current MDD (N=2053; age range 21–69 years; 66.8% females). Probable ADHD was defined as having current ADHD symptoms on the Conners Adult ADHD Rating Scale and a positive score on childhood or early-adolescent ADHD indicators. We examined ADHD symptom rates across (i) those with and without lifetime MDD, (ii) clinical characteristics of MDD including severity, course and outcomes, (iii) clinical stages of MDD. Results (i) The prevalence of ADHD symptoms was 0.4% in healthy controls, 5.7% in remitted MDD and 22.1% in current MDD (OR=4.5; 95% CI 3.1–6.5). (ii) ADHD symptom rates and odds were significantly increased among those with more severe depression (29.4%; OR=6.8; 95% CI 2.9–16.1), chronic depression (21.8%; OR=3.8; 95% CI 2.5–5.7), earlier age of onset of depressive symptoms (9.9%; OR=1.5; 95% CI 1.0–2.3), and comorbid anxiety disorders (29.0%; OR=3.4; 95% CI 2.0–5.7). (iii) ADHD symptom rates increased across clinical stages of MDD, up to 22.5% in chronic MDD. Limitations We used self-reports on ADHD symptoms. Also, clinical staging models have not yet been validated for mental disorders. Conclusions ADHD symptoms are very common among MDD patients, especially among those in recurrent and chronic stages of MDD. Considering ADHD may be an important step forward in improving the treatment of depression.

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Prevalence and treatment of common mental disorders in the English national population, 1993–2007

Prevalence and treatment of common mental disorders in the English national population, 1993–2007 | Depression Research | Scoop.it

Background The National Psychiatric Morbidity Surveys include English cross-sectional household samples surveyed in 1993, 2000 and 2007.  Aims To evaluate frequency of common mental disorders (CMDs), service contact and treatment.MethodCommon mental disorders were identified with the Clinical Interview Schedule – Revised (CIS-R). Service contact and treatment were established in structured interviews.  Results There were 8615, 6126 and 5385 participants aged 16–64. Prevalence of CMDs was consistent (1993: 14.3%; 2000: 16.0%; 2007: 16.0%), as was past-year primary care physician contact for psychological problems (1993: 11.3%; 2000: 12.0%; 2007: 11.7%).  Antidepressant receipt in people with CMDs more than doubled between 1993 (5.7%) and 2000 (14.5%), with little further increase by 2007 (15.9%). Psychological treatments increased in successive surveys. Many with CMDs received no treatment.  Conclusions Reduction in prevalence did not follow increased treatment uptake, and may require universal public health measures together with individual pharmacological, psychological and computer-based interventions.

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Adolescent depression, adult mental health and psychosocial outcomes at 30 and 35 years

Adolescent depression, adult mental health and psychosocial outcomes at 30 and 35 years | Depression Research | Scoop.it

Background There is limited information on long-term outcomes of adolescent depression. This study examines the associations between severity of depression in adolescence and a broad array of adult functional outcomes. Method Data were gathered as part of the Christchurch Health and Development Study, a 35-year longitudinal study of a birth cohort of 1265 children born in Christchurch, New Zealand in 1977. Severity of depression at age 14–16 years was classified into three levels according to DSM symptom criteria for major depression (no depression/sub-threshold symptoms/major depression). This classification was related to adult functional outcomes assessed at ages 30 and 35 years using a generalized estimating equation modeling approach. Outcome measures spanned domains of mental disorder, education/economic circumstances, family circumstances and partner relationships. Results There were modest but statistically significant bivariate associations between adolescent depression severity and most outcomes. After covariate adjustment there remained weak but significant (p < 0.05) associations with rates of major depression, anxiety disorder, illicit substance abuse/dependence, any mental health problem and intimate partner violence (IPV) victimization. Estimates of attributable risk for these outcomes ranged from 3.8% to 7.8%. For two outcomes there were significant (p < 0.006) gender interactions such that depression severity was significantly related to increased rates of unplanned pregnancy and IPV victimization for females but not for males. Conclusions The findings reinforce the importance of the individual/family context in which adolescent depression occurs. When contextual factors and probable maturational effects are taken into account the direct effects of adolescent depression on functioning in mature adulthood appear to be very modest.

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Ultra-Low-Dose Buprenorphine as a Time-Limited Treatment for Severe Suicidal Ideation: A Randomized Controlled Trial

Ultra-Low-Dose Buprenorphine as a Time-Limited Treatment for Severe Suicidal Ideation: A Randomized Controlled Trial | Depression Research | Scoop.it

Objective: Suicidal ideation and behavior currently have no quick-acting pharmacological treatments that are suitable for independent outpatient use. Suicidality is linked to mental pain, which is modulated by the separation distress system through endogenous opioids. The authors tested the efficacy and safety of very low dosages of sublingual buprenorphine as a time-limited treatment for severe suicidal ideation.  Method: This was a multisite randomized double-blind placebo-controlled trial of ultra-low-dose sublingual buprenorphine as an adjunctive treatment. Severely suicidal patients without substance abuse were randomly assigned to receive either buprenorphine or placebo (in a 2:1 ratio), in addition to their ongoing individual treatments. The primary outcome measure was change in suicidal ideation, as assessed by the Beck Suicide Ideation Scale at the end of each of 4 weeks of treatment.  Results: Patients who received ultra-low-dose buprenorphine (initial dosage, 0.1 mg once or twice daily; mean final dosage=0.44 mg/day; N=40) had a greater reduction in Beck Suicide Ideation Scale scores than patients who received placebo (N=22), both after 2 weeks (mean difference −4.3, 95% CI=−8.5, −0.2) and after 4 weeks (mean difference=−7.1, 95% CI=−12.0, −2.3). Concurrent use of antidepressants and a diagnosis of borderline personality disorder did not affect the response to buprenorphine. No withdrawal symptoms were reported after treatment discontinuation at the end of the trial.  Conclusions: The time-limited, short-term use of very low dosages of sublingual buprenorphine was associated with decreased suicidal ideation in severely suicidal patients without substance abuse. Further research is needed to establish the efficacy, safety, dosing, and appropriate patient populations for this experimental treatment.

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'In my life antidepressants have been…’: a qualitative analysis of users’ experiences with antidepressants.

'In my life antidepressants have been…’: a qualitative analysis of users’ experiences with antidepressants. | Depression Research | Scoop.it

(Available in free full text)  Background: While mental health professionals have focused on concerns about whether antidepressants work on a neurochemical level it is important to understand the meaning this medication holds in the lives of people who use it. This study explores diversity in the experience of antidepressant users.  Methods: One thousand seven hundred forty-seven New Zealand antidepressant users responded to an open-ended question about their experience of antidepressants. This was analysed using content and thematic analysis.  Results: There was considerable diversity in participants’ responses including positive (54 %), negative (16 %) and mixed (28 %) experiences with antidepressants. Those with positive experiences saw antidepressants as a necessary treatment for a ‘disease’, a life saver, a way of meeting social obligations, dealing with difficult circumstances or a stepping stone to further help. Negative themes described antidepressants as being ineffective, having unbearable side effects, undermining emotional authenticity, masking real problems and reducing the experience of control. Mixed experience themes showed how participants weighed up the unpleasant side effects against the benefits, felt calmer but less like themselves, struggled to find the one or dosage and felt stuck with continuing on antidepressants when they wished to stop.  Conclusions: Mental health professions need to recognize that antidepressants are not a ‘one size fits all’ solution.

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Blue-blocking glasses as additive treatment for mania: a randomized placebo-controlled trial

Blue-blocking glasses as additive treatment for mania: a randomized placebo-controlled trial | Depression Research | Scoop.it

(Available in free full text) Objectives The discovery of the blue lightsensitive retinal photoreceptor responsible for signaling daytime to the brain suggested that light to the circadian system could be inhibited by using blue-blocking orange tinted glasses. Blue-blocking (BB) glasses are a potential treatment option for bipolar mania. We examined the effectiveness of BB glasses in hospitalized patients with bipolar disorder in a manic state. Methods In a single-blinded, randomized, placebo-controlled trial (RCT), eligible patients (with bipolar mania; age 18–70 years) were recruited from five clinics in Norway. Patients were assigned to BB glasses or placebo (clear glasses) from 6 p.m. to 8 a.m. for 7 days, in addition to treatment as usual. Symptoms were assessed daily by use of the Young Mania Rating Scale (YMRS). Motor activity was assessed by actigraphy, and compared to data from a healthy control group. Wearing glasses for one evening/night qualified for inclusion in the intention-to-treat analysis. Results From February 2012 to February 2015, 32 patients were enrolled. Eight patients dropped out and one was excluded, resulting in 12 patients in the BB group and 11 patients in the placebo group. The mean decline in YMRS score was 14.1 [95% confidence interval (CI): 9.7–18.5] in the BB group, and 1.7 (95% CI: −4.0 to 7.4) in the placebo group, yielding an effect size of 1.86 (Cohen's d). In the BB group, one patient reported headache and two patients experienced easily reversible depressive symptoms. Conclusions This RCT shows that BB glasses are effective and feasible as add-on treatment for bipolar mania.

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