been more encouraging. The trial should therefore not be regarded as a definitive dismissal of the promise of these or related agents. 3 Theoretically, depression in bipolar disorder is a more heterogeneous construct than mania, which is more monothematically biological in its causation. Depression is driven by a far wider array and admixture of biological factors, consequences of behaviours while manic, losses in domains such as educational and vocational horizons, relationships, personality, finances, guilt, stigma, and self-stigma, among others. Therefore, it is arguably ambitious at the outset to expect a singular biological therapy targeting one biological marker of the disorder to address all phenotypes of this heterogeneous clinical presentation. The complexity of bipolar depression might be an explanation more broadly for the relatively common failure of singular treatment approaches. These failures suggest that polyvalent and personalised therapies predicated on individualised profiles are needed to select from the diverse pharmacological, neurostimulatory, nutraceutical, lifestyle, and psychological approaches that are available. 10 In sum, this might not be the last word on the potential role of anti-inflammatory drugs in the treatment of bipolar depression, but notwithstanding the methodological issues that accompany any clinical trial, the promise of targeting the inflammation pathway in the management of this challenging condition is today somewhat weaker.

Background The COVID-19 pandemic is having profound mental health consequences for many people. Concerns have been expressed that, at their most extreme, these consequences could manifest as increased suicide rates. We aimed to assess the early effect of the COVID-19 pandemic on suicide rates around the world. MethodsWe sourced real-time suicide data from countries or areas within countries through a systematic internet search and recourse to our networks and the published literature. Between Sept 1 and Nov 1, 2020, we searched the official websites of these countries' ministries of health, police agencies, and government-run statistics agencies or equivalents, using the translated search terms "suicide" and "cause of death", before broadening the search in an attempt to identify data through other public sources. Data were included from a given country or area if they came from an official government source and were available at a monthly level from at least Jan 1, 2019, to July 31, 2020. Our internet searches were restricted to countries with more than 3 million residents for pragmatic reasons, but we relaxed this rule for countries identified through the literature and our networks. Areas within countries could also be included with populations of less than 3 million. We used an interrupted time-series analysis to model the trend in monthly suicides before COVID-19 (from at least Jan 1, 2019, to March 31, 2020) in each country or area within a country, comparing the expected number of suicides derived from the model with the observed number of suicides in the early months of the pandemic (from April 1 to July 31, 2020, in the primary analysis).Findings We sourced data from 21 countries (16 high-income and five upper-middle-income countries), including whole-country data in ten countries and data for various areas in 11 countries). Rate ratios (RRs) and 95% CIs based on the observed versus expected numbers of suicides showed no evidence of a significant increase in risk of suicide since the pandemic began in any country or area. There was statistical evidence of a decrease in suicide compared with the expected number in 12 countries or areas: New South Wales

The results highlight the importance in a suicide prevention strategy of early intervention after an episode of self-harm. Treatment should include attention to physical illness, alcohol problems, and living circumstances. Self-harm appears to confer a particularly high risk of suicide in female patients.

Objectives To examine temporal trends in sex and age specific incidence of self harm in children and adolescents, clinical management patterns, and risk of cause specific mortality following an index self harm episode at a young age. Design Population based cohort study. Setting UK Clinical Practice Research Datalink—electronic health records from 674 general practices, with practice level deprivation measured ecologically using the index of multiple deprivation. Patients from eligible English practices were linked to hospital episode statistics (HES) and Office for National Statistics (ONS) mortality records. Participants For the descriptive analytical phases we examined data pertaining to 16 912 patients aged 10-19 who harmed themselves during 2001-14. For analysis of cause specific mortality following self harm, 8638 patients eligible for HES and ONS linkage were matched by age, sex, and general practice with up to 20 unaffected children and adolescents (n=170 274). Main outcome measures In the first phase, temporal trends in sex and age specific annual incidence were examined. In the second phase, clinical management was assessed according to the likelihood of referral to mental health services and psychotropic drug prescribing. In the third phase, relative risks of all cause mortality, unnatural death (including suicide and accidental death), and fatal acute alcohol or drug poisoning were estimated as hazard ratios derived from stratified Cox proportional hazards models for the self harm cohort versus the matched unaffected comparison cohort. Results The annual incidence of self harm was observed to increase in girls (37.4 per 10 000) compared with boys (12.3 per 10 000), and a sharp 68% increase occurred among girls aged 13-16, from 45.9 per 10 000 in 2011 to 77.0 per 10 000 in 2014. Referrals within 12 months of the index self harm episode were 23% less likely for young patients registered at the most socially deprived practices, even though incidences were considerably higher in these localities. Children and adolescents who harmed themselves were approximately nine times more likely to die unnaturally during follow-up, with especially noticeable increases in risks of suicide (deprivation adjusted hazard ratio 17.5, 95% confidence interval 7.6 to 40.5) and fatal acute alcohol or drug poisoning (34.3, 10.2 to 115.7). Conclusions Gaining a better understanding of the mechanisms responsible for the recent apparent increase in the incidence of self harm among early-mid teenage girls, and coordinated initiatives to tackle health inequalities in the provision of services to distressed children and adolescents, represent urgent priorities for multiple public agencies.

Helped to interpret the analyses and write the report Conflict of interest statements: NK and TK were chair and facilitator, respectively, of NICE clinical guideline 133 on self-harm (longer term management). The other authors were members of the guideline development group. NK sits on the Department of Health's (England) National Suicide Prevention Strategy Advisory Group. Some authors were also co-authors on primary studies included in the review.Role of funding source: This study was funded in part by NICE during the development of the NICE guideline for self-harm: longer term management Ethics committee approval: Not applicable PRISMA statement: Please refer to online appendix. AbstractBackground: Suicide and self-harm are major public health problems. People with a history of self-harm are at a far greater risk of suicide than the general population. However, the relationship between self-harm and suicide is complex. We have undertaken the first systematic review and meta-analysis of prospective studies of risk factors and risk assessment scales to predict suicide following self-harm, undertaken as part of the development of the National Institute for Health and Care Excellence (NICE) guideline.

Objectives To determine the effects of a brief psychological intervention (brief psychodynamic interpersonal therapy) for patients after deliberate self poisoning compared with usual treatment. To compare the impact of the active intervention and usual treatment on patients' satisfaction with care.

Non-suicidal self-injury (NSSI) is a term that is becoming popular especially in North America and it has been proposed as a new diagnosis in DSM-5. In this paper we consider what self-harm research can tell us about the concept of NSSI and examine the potential pitfalls of introducing NSSI into clinical practice.

Strategies to reduce suicide by hanging should focus on the prevention of suicide in controlled environments, the emergency management of 'near-hanging' and on the primary prevention of suicide in general. More research is required to better understand the recent rise in popularity of this method.