Mirroring everyday clinical practice in clinical trial design: a new concept to improve the external validity of randomized double-blind placebo-controlled trials in the pharmacological treatment of major depression

Background: Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient selection. Discussion: To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population. Summary: We propose a list of measures to be taken to improve the external validity of double-blind, placebocontrolled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the outcome itself

Effect of a barrier at Bloor Street Viaduct on suicide rates in Toronto: natural experiment

Objective To determine whether rates of suicide changed in Toronto after a barrier was erected at Bloor Street Viaduct, the bridge with the world’s second highest annual rate of suicide by jumping after Golden Gate Bridge in San Francisco

Interventions for treating depression after stroke

Background: Depression is an important consequence of stroke that impacts on recovery yet is often not detected or inadequately treated. This is an update of a Cochrane review first published in 2004. Objectives: To determine whether pharmaceutical, psychological, or electroconvulsive treatment (ECT) of depression in patients with stroke can improve outcome. Search strategy: We searched the trials registers of the Cochrane Stroke Group (last searched October 2007) and the Cochrane Depression Anxiety and Neurosis Group (last searched February 2008). In addition, we searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2008), MEDLINE (1966 to May 2006), EMBASE (1980 to May 2006), CINAHL (1982 to May 2006), PsycINFO (1967 to May 2006) and other databases. We also searched reference lists, clinical trials registers, conference proceedings and dissertation abstracts, and contacted authors, researchers and pharmaceutical companies. Selection criteria: Randomised controlled trials comparing pharmaceutical agents with placebo, or various forms of psychotherapy or ECT with standard care (or attention control), in patients with stroke, with the intention of treating depression. Data collection and analysis: Two review authors selected trials for inclusion and assessed methodological quality; three review authors extracted, cross-checked and entered data. Primary analyses were the prevalence of diagnosable depressive disorder at the end of treatment. Secondary outcomes included depression scores on standard scales, physical function, death, recurrent stroke and adverse effects. Main results: Sixteen trials (17 interventions), with 1655 participants, were included in the review. Data were available for 13 pharmaceutical agents, and four trials of psychotherapy. There were no trials of ECT. The analyses were complicated by the lack of standardised diagnostic and outcome criteria, and differing analytic methods. There was some evidence of benefit of pharmacotherapy in terms of a complete remission of depression and a reduction (improvement) in scores on depression rating scales, but there was also evidence of an associated increase in adverse events. There was no evidence of benefit of psychotherapy. Authors' conclusions: A small but significant effect of pharmacotherapy (not psychotherapy) on treating depression and reducing depressive symptoms was found, as was a significant increase in adverse events. More research is required before recommendations can be made about the routine use of such treatments

Long-range temporal correlations of broadband EEG oscillations for depressed subjects following different hemispheric cerebral infarction

Abnormal long-range temporal correlation (LRTC) in EEG oscillation has been observed in several brain pathologies and mental disorders. This study examined the relationship between the LRTC of broadband EEG oscillation and depression following cerebral infarction with different hemispheric lesions to provide a novel insight into such depressive disorders. Resting EEGs of 16 channels in 18 depressed (9 left and 9 right lesions) and 21 non-depressed (11 left and 10 right lesions) subjects following cerebral infarction and 19 healthy control subjects were analysed by means of detrended fluctuation analysis, a quantitative measurement of LRTC. The difference among groups and the correlation between the severity of depression and LRTC in EEG oscillation were investigated by statistical analysis. The results showed that LRTC of broadband EEG oscillations in depressive subjects was still preserved but attenuated in right hemispheric lesion subjects especially in left pre-frontal and right inferior frontal and posterior temporal regions. Moreover, an association between the severity of psychiatric symptoms and the attenuation of the LRTC was found in frontal, central and temporal regions for stroke subjects with right lesions. A high discriminating ability of the LRTC in the frontal and central regions to distinguish depressive from non-depressive subjects suggested potential feasibility for LRTC as an assessment indicator for depression following right hemispheric cerebral infarction. Different performance of temporal correlation in depressed subjects following the two hemispheric lesions implied complex association between depression and stroke lesion location.</p

Suicide risk and prevention during the COVID-19 pandemic:one year on

Emerging data from high and upper-middle-income countries indicate that suicide rates generally did not increase during the initial months of the COVID-19 pandemic, yet the pandemic's impact on suicide is complex. We discuss the nuances of this relationship, how it may evolve over time, and describe the specific steps that governments and societies must take to mitigate harm and prevent suicides in the late stages and aftermath of the pandemic

Mood instability and irritability as core symptoms of major depression : an exploration using Rasch analysis

Background: Mood instability (MI) and irritability are related to depression but are not considered core symptoms. Instruments typically code clusters of symptoms that are used to define syndromic depression, but the place of MI and irritability has been under-investigated. Whether they are core symptoms can be examined using Rasch analysis. Method: We used the UK Psychiatric Morbidity Survey 2000 data (n = 8,338) to determine whether the nine ICD/DSM symptoms, plus MI and irritability, constitute a valid depression scale. Rasch analysis was used, a method concerned with ensuring that items constitute a robust scale and tests whether the count of symptoms reflects an underlying interval-level measure. Two random samples of 500 were drawn, serving as calibration and validation samples. As part of the analysis, we examined whether the candidate symptoms were unidimensional, followed a Guttman pattern, were locally independent, invariant with respect to age and sex, and reliably distinguished different levels of depression severity. Results: A subset of five symptoms (sad, no interest, sleep, cognition, suicidal ideas) together with mood instability and irritability satisfactorily fits the Rasch model. However, these seven symptoms do not separate clinically depressed persons from the rest of the population with adequate reliability (Cronbach α = 0.58; Person Separation Index = 0.35), but could serve as a basis for scale development. Likewise, the original nine DSM depression symptoms failed to achieve satisfactory reliability (Cronbach α = 0.67; Person Separation Index = 0.51). Limitations: The time frame over which symptoms were experienced varied, and some required recall over the last year. Symptoms other than those examined here might also be core depression symptoms. Conclusion: Mood instability and irritability are candidate core symptoms of the depressive syndrome and should be part of its clinical assessment