THE ACUTE EFFECTS OF ACCELERATED REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION ON SUICIDE RISK IN UNIPOLAR DEPRESSION: PRELIMINARY RESULTS

Background: Suicide is a major health concern. Effective acute interventions are lacking. Recent studies have suggested an acute decrease of suicidal ideations following repetitive Transcranial Magnetic Stimulation (rTMS). However, placebo effects could not be excluded. We aimed to evaluate the acute effect of accelerated intermittent theta burst stimulation (TBS) on suicide risk in depression. Subjects and methods: In 12 suicidal therapy-resistant depressed patients accelerated intermittent TBS was delivered on the left dorsolateral prefrontal cortex in a randomized, sham-controlled cross-over fashion. Patients received 20 sessions spread over 4 days. The change in severity of suicidal ideation was measured by the Beck Scale of Suicidal Ideation (SSI) before and after treatment. Results: We found a significant decrease of SSI score over time; unrelated to active or sham stimulation. Furthermore, the attenuation of suicidal thinking was not merely related to depression severity changes caused by TBS. Conclusions: Accelerated TBS treatment in depressed suicidal patients was found to be safe and well tolerated and may have the potential to acutely decrease suicidal ideations. However, the efficacy compared to sham has not yet been proven and further shamcontrolled research including longer follow-up is needed to substantiate these preliminary findings

Epistasis between 5-HTTLPR and ADRA2B polymorphisms influences attentional bias for emotional information in healthy volunteers

Individual differences in emotional processing are likely to contribute to vulnerability and resilience to emotional disorders such as depression and anxiety. Genetic variation is known to contribute to these differences but they remain incompletely understood. The serotonin transporter (5-HTTLPR) and alpha(2B)-adrenergic autoreceptor (ADRA2B) insertion/deletion polymorphisms impact on two separate but interacting monaminergic signalling mechanisms that have been implicated in both emotional processing and emotional disorders. Recent studies suggest that the 5-HTTLPR s allele is associated with a negative attentional bias and an increased risk of emotional disorders. However, such complex behavioural traits are likely to exhibit polygenicity, including epistasis. This study examined the contribution of the 5-HTTLPR and ADRA2B insertion/deletion polymorphisms to attentional biases for aversive information in 94 healthy male volunteers and found evidence of a significant epistatic effect (p < 0.001). Specifically, in the presence of the 5-HTTLPR s allele, the attentional bias for aversive information was attenuated by possession of the ADRA2B deletion variant whereas in the absence of the s allele, the bias was enhanced. These data identify a cognitive mechanism linking genotype-dependent serotonergic and noradrenergic signalling that is likely to have implications for the development of cognitive markers for depression/anxiety as well as therapeutic drug effects and personalized approaches to treatment

Psychosocial interventions for people who self-harm:Methodological issues involved in trials to evaluate effectiveness

We have assessed the methodological quality of randomized controlled trials (RCTs) of interventions to prevent self-harm repetition and suicide. Trials were identified in two systematic reviews of RCTs of psychosocial treatments following a recent (within six months) episode of self-harm indexed in any of five electronic databases (CCDANCTR-Studies and References, CENTRAL, Medline, Embase, and PsycINFO) between 1 January, 1998 and 29 April, 2015. A total of 66 trials were included, 55 in adults and 11 in children and adolescents. While evidence for efficacy of some approaches has grown, there were few trials from low-to-middle income countries, little information on interventions for males, information on the control condition was often limited, data on suicides were often not reported, and, while trials have increased in size in recent years, most have included too few participants to detect clinically significant results. There are major limitations in many trials of interventions for individuals who self-harm. Improved methodology, especially with regard to study size, provision of details of control therapy, and evaluation of key outcomes, would enhance the evidence base for clinicians and service users

Gender distribution of suicide attempts among immigrant groups in European countries—an international perspective

Background: Studies report high rates of suicide attempts for female immigrants. This study assesses variations in the distribution of suicide attempts across gender in immigrant and non-immigrant groups in Europe. Method: Data on 64 native and immigrant groups, including 17 662 local and 3755 immigrant person-cases collected, between 1989 and 2003, in 24 million person-years were derived from the WHO/EURO Multicentre Study on Suicidal Behaviour. Female-to-male ratios of suicide attempt rates (SARs) were calculated for all groups. Results: The cases were combined into four major categories: hosts; European and other Western immigrants; non-European immigrants; and Russian immigrants. The non-European immigrants included higher female SARs than the Europeans, both hosts and immigrants. Unlike the other groups, the majority of suicide attempters among the Russian immigrants in Estonia and Estonian hosts were male. This was also true for immigrants from Curaçao, Iran, Libya and Sri Lanka. When the single groups with a male majority were excluded, the correlation between female and male SARs was relatively high among the European immigrants (r = 0.74, P < 0.0005) and lower among the non-European immigrants (r = 0.55, P < 0.03). Generalized estimating equation analysis yielded a highly significant difference (P < 0.0005) in gender ratios of suicide attempts between hosts (ratio 1.52) and both non-European immigrants (ratio 2.32) and Russian immigrants (0.68), but not the European immigrants. Conclusions: The higher suicide attempt rates in non-European immigrant females compared with males may be indicative of difficulties in the acculturation processes in Europe. Further understanding of factors underlying suicidal behaviour in immigrant and minority groups is necessary for planning effective prevention strategie

Immigration and recommended care after a suicide attempt in Europe: equity or bias?

This report describes the investigation of care recommendations in the medical system across European countries to immigrants who attempted suicide. Data from seven European countries with 8865 local and 2921 immigrant person-cases were derived from the WHO/EURO Multicentre Study on Suicidal Behaviour and ensuing MONSUE (Monitoring Suicidal Behaviour in Europe) project. The relationship between immigrant status and type of aftercare recommended was analysed with binary logistic regression, adjusting for gender, age, method of attempt and the Centre collecting the data. Clear disparities were identified in the care recommendation practices toward immigrants, compared with hosts, over and above differing policies by the European Centre

Pharmacological interventions for self-harm in adults

BackgroundSelf-harm (SH; intentional self-poisoning or self-injury) is common, often repeated, and strongly associated with suicide. This is an update of a broader Cochrane review on psychosocial and pharmacological treatments for deliberate SH, first published in 1998 and previously updated in 1999. We have now divided the review in to three separate reviews. This review is focused on pharmacological interventions in adults who self harm.ObjectivesTo identify all randomised controlled trials of pharmacological agents or natural products for SH in adults, and to conduct meta-analyses (where possible) to compare the effects of specific treatments with comparison types of treatment (e.g., placebo/alternative pharmacological treatment) for SH patients.Search methodsFor this update the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) Trials Search Co-ordinator searched the CCDAN Specialised Register (September 2014). Additional searches of MEDLINE, EMBASE, PsycINFO, and CENTRAL were conducted to October 2013.Selection criteriaWe included randomised controlled trials comparing pharmacological treatments or natural products with placebo/alternative pharmacological treatment in individuals with a recent (within six months) episode of SH resulting in presentation to clinical services.Data collection and analysisWe independently selected trials, extracted data, and appraised trial quality. For binary outcomes, we calculated odds ratios (ORs) and their 95% confidence intervals (CIs). For continuous outcomes we calculated the mean difference (MD) and 95% CI. Meta-analysis was only possible for one intervention (i.e. newer generation antidepressants) on repetition of SH at last follow-up. For this analysis, we pooled data using a random-effects model. The overall quality of evidence for the primary outcome was appraised for each intervention using the GRADE approach.Main resultsWe included seven trials with a total of 546 patients. The largest trial included 167 participants. We found no significant treatment effect on repetition of SH for newer generation antidepressants (n = 243; k = 3; OR 0.76, 95% CI 0.42 to 1.36; GRADE: low quality of evidence), low-dose fluphenazine (n = 53; k = 1; OR 1.51, 95% CI 0. 50 to 4.58; GRADE: very low quality of evidence), mood stabilisers (n = 167; k = 1; OR 0.99, 95% CI 0.33 to 2.95; GRADE: low quality of evidence), or natural products (n = 49; k = 1; OR 1.33, 95% CI 0.38 to 4.62; GRADE: low quality of evidence). A significant reduction in SH repetition was found in a single trial of the antipsychotic flupenthixol (n = 30; k = 1; OR 0.09, 95% CI 0.02 to 0.50), although the quality of evidence for this trial, according to the GRADE criteria, was very low. No data on adverse effects, other than the planned outcomes relating to suicidal behaviour, were reported.Authors&rsquo; conclusionsGiven the low or very low quality of the available evidence, and the small number of trials identified, it is not possible to make firm conclusions regarding pharmacological interventions in SH patients. More and larger trials of pharmacotherapy are required. In view of an indication of positive benefit for flupenthixol in an early small trial of low quality, these might include evaluation of newer atypical antipsychotics. Further work should include evaluation of adverse effects of pharmacological agents. Other research could include evaluation of combined pharmacotherapy and psychological treatment.<br /

Psychosocial interventions for self-harm in adults

Background: Self-harm (SH; intentional self-poisoning or self-injury) is common, often repeated, and associated with suicide. This is an update of a broader Cochrane review first published in 1998, previously updated in 1999, and now split into three separate reviews. This review focuses on psychosocial interventions in adults who engage in self-harm.Objectives: To assess the effects of specific psychosocial treatments versus treatment as usual, enhanced usual care or other forms of psychological therapy, in adults following SH.Search methods: The Cochrane Depression, Anxiety and Neurosis Group (CCDAN) trials coordinator searched the CCDAN Clinical Trials Register (to 29 April 2015). This register includes relevant randomised controlled trials (RCTs) from: the Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date).Selection criteria: We included RCTs comparing psychosocial treatments with treatment as usual (TAU), enhanced usual care (EUC) or alternative treatments in adults with a recent (within six months) episode of SH resulting in presentation to clinical services.Data collection and analysis: We used Cochrane's standard methodological procedures

Treatment as usual (TAU) as a control condition in trials of cognitive behavioural-based psychotherapy for self-harm:impact of content and quality on outcomes in a systematic review

Background: Randomized controlled trials (RCTs) are the mainstay of evaluations of the efficacy of psychosocial interventions. In a recent Cochrane systematic review we analysed the efficacy of cognitive behavioural-based psychotherapies compared to treatment as usual (TAU) in adults who self-harm. In this study we examine the content and reporting quality of TAU in these trials and their relationship to outcomes. Methods: Five electronic databases (CCDANCTR-Studies and References, CENTRAL, MEDLINE, EMBASE, and PsycINFO) were searched for RCTs, indexed between 1 January 1998 and 30 April 2015, of cognitive-behavioural interventions compared to TAU for adults following a recent (within six months) episode of self-harm. Comparisons were made between outcomes for trials which included different categories of TAU, which were grouped as: multidisciplinary treatment, psychotherapy only, pharmacotherapy only, treatment by primary care physician, minimal contact, or unclear. Results: 18 trials involving 2433 participants were included. The content and reporting quality of TAU varied considerably between trials. The apparent effectiveness of cognitive behavioural psychotherapy varied according to TAU reporting quality and content. Specifically, effects in favour of cognitive-behavioural psychotherapy were strongest in trials in which TAU content was not clearly described (Odds Ratio: 0.29, 95% Confidence Interval 0.15–0.62; three trials) compared to those in which TAU comprised multidisciplinary treatment (Odds Ratio: 0.79, 95% CI 0.63 to 0.97; 12 trials). Limitations: The included trials had high risk of bias with respect to participant and clinical personnel blinding, and unclear risk of bias for selective outcome reporting. Conclusions: TAU content and quality represents an important source of heterogeneity between trials of psychotherapeutic interventions for prevention of self-harm. Before clinical trials begin, researchers should plan to carefully describe both aspects of TAU to improve the overall quality of investigations.</p