Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials

Objective To establish whether an association exists between use of selective serotonin reuptake inhibitors (SSRIs) and suicide attempts.Design Systematic review of randomised controlled trials.Data sources Medline and the Cochrane Collaboration''s register of controlled trials (November 2004) for trials produced by the Cochrane depression, anxiety, and neurosis group.Selection of studies Studies had to be randomised controlled trials comparing an SSRI with either placebo or an active non-SSRI control. We included clinical trials that evaluated SSRIs for any clinical condition. We excluded abstracts, crossover trials, and all trials whose follow up was less than one week.Results Seven hundred and two trials met our inclusion criteria. A significant increase in the odds of suicide attempts (odds ratio 2.28, 95% confidence 1.14 to 4.55, number needed to treat to harm 684) was observed for patients receiving SSRIs compared with placebo. An increase in the odds ratio of suicide attempts was also observed in comparing SSRIs with therapeutic interventions other than tricyclic antidepressants (1.94, 1.06 to 3.57, 239). In the pooled analysis of SSRIs versus tricyclic antidepressants, we did not detect a difference in the odds ratio of suicide attempts (0.88, 0.54 to 1.42).Discussion Our systematic review, which included a total of 87 650 patients, documented an association between suicide attempts and the use of SSRIs. We also observed several major methodological limitations in the published trials. A more accurate estimation of risks of suicide could be garnered from investigators fully disclosing all events.     

The population impact on incidence of suicide and non-fatal self harm of regulatory action against the use of selective serotonin reuptake inhibitors in under 18s in the United Kingdom: ecological study

Objective To investigate the population impact on the incidence of suicide and non-fatal self harm of regulatory action in 2003 to restrict the use of selective serotonin reuptake inhibitors (SSRIs) in under 18s.Design Ecological time series study.Setting United Kingdom.Populations Young people in the UK aged 12-19 years (prescribing trends), in England and Wales aged 12-17 years (mortality), and in England aged 12-17 years (hospital admissions).Main outcome measures Deaths from suicide and hospital admissions for self harm.Results Antidepressant prescribing doubled between 1999 and 2003 but fell to the 1999 level between 2004 and 2005. These large changes in prescribing did not seem to be associated with temporal trends in suicide or self harm. In the years 1993 to 2005 the annual percentage reduction for suicide among 12-17 year olds was −3.9% (95% confidence interval −6.2% to −1.5%) in males and −3.0% (−6.6% to 0.6%) in females, with no indication of a substantial change in this rate of decrease during that period. Similarly, hospital admission rates for self harm in the years 1999 to 2005 indicated an annual percentage increase for males of 1.1% (−0.5% to 2.7%) and for females of 5.7% (3.6% to 7.8%), again with no statistical evidence of a change in rate after the regulatory action.Conclusions The noticeable reduction in prescribing of antidepressants since regulatory action in 2003 to restrict the use of SSRIs in under 18s does not seem to have been associated with changes in suicidal behaviour in young people. Specifically, these data for England do not indicate that reductions in antidepressant use have led to an increase in suicidal behaviour.     

Selective serotonin reuptake inhibitors and risk of suicide: a systematic review of observational studies

Background

It is unclear whether the use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressant drugs reduce the risk of suicide in people with depression. We explored the association between exposure to SSRIs and risk of suicide completion or attempt.

Methods

We conducted a systematic review of observational studies that reported completed or attempted suicide in depressed individuals who were exposed to SSRIs compared with those who were not exposed to antidepressants. We assessed the overall risk of completed or attempted suicide.

Results

Eight studies involving more than 200 000 patients with moderate or severe depression were included in the meta-analysis. Although exposure to SSRIs increased the risk of completed or attempted suicide among adolescents (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.51–2.44), the risk was decreased among adults (OR 0.57, 95% CI 0.47–0.70). Among people aged 65 or more years, exposure to SSRIs had a protective effect (OR 0.46, 95% CI 0.27–0.79). Sensitivity analyses did not change these findings. In particular, for studies that used completed suicide as an outcome, exposure to SSRIs was associated with increased risk among adolescents (OR 5.81, 95% CI 1.57–21.51) and decreased risk among adults (OR 0.66, 95% CI 0.52–0.83) and older people (OR 0.53, 95% CI 0.26–1.06).

Interpretation

Based on data from observational studies, use of SSRIs may be associated with a reduced risk of suicide in adults with depression. Among adolescents, use of SSRIs may increase suicidality.There is uncertainty about the safety of selective serotonin reuptake inhibitors (SSRIs), which may cause worsening of suicidal thoughts in vulnerable people.^1,2 In 2005, a systematic review of published randomized controlled trials comparing SSRIs with another active treatment or placebo found an almost 2-fold increase in the odds of fatal and nonfatal suicide attempts among those exposed to SSRIs.³ No increase in risk was observed, however, when only fatal suicide attempts were included. Another systematic review,⁴ which included both published and unpublished randomized controlled trials submitted by pharmaceutical companies to the safety review of the Medicine and Healthcare products Regulatory Agency compared the use of SSRIs and placebo in adults with depression and other clinical conditions.⁴ This review showed no evidence of increased risk of completed suicide and only weak evidence of increased risk of self-harm.More recently, the US Food and Drug Administration (FDA) performed a meta-analysis of individual patient data from 372 randomized placebo-controlled trials of antidepressants with a total of nearly 100 000 patients.⁵ This study reported that the incidence of reported suicidal behaviour was strongly related to age.⁵ The risk associated with antidepressant use relative to placebo was increased among patients aged 25 or fewer years, and it was reduced among patients aged 65 or more years.⁵ The risk among patients aged 25–64 years was neutral; however, risk was reduced when suicidal behaviour and ideation were considered together.⁵ Based on these findings, in May 2007 the FDA ordered that all antidepressant drugs carry an expanded black-box warning on their label that included information about increased risk of suicidal behaviour in young adults aged 18–24 years.^6,7A controversial point of the FDA analysis is that the included trials were not primarily designed to measure suicidality (a composite outcome that includes suicide ideas, preparatory acts, suicide attempts and deaths by suicide).⁵ Of all suicidality events, less than 30% were serious suicide attempts or deaths. Additionally, considering that suicidality was self-reported rather than observed by others in most clinical trials, it is possible that antidepressant treatment, particularly in younger individuals, enhanced communication about suicidality, which may have allowed them to become more articulate and open about their thoughts and actions. Alternatively, antidepressant treatment might have enhanced communication about suicidality in all age groups, but increased attention to adverse effects might have led to enhanced detection of suicidality in younger individuals.⁵It is unlikely that individual randomized trials will be designed to primarily investigate the effect of antidepressant use on suicidality, and future systematic reviews of clinical trial data will not be able to overcome the limitations of the FDA analysis. Therefore, we sought to further explore the association between SSRI exposure and risk of completed or attempted suicide by conducting a systematic review and meta-analysis of observational studies. By including a large, broad spectrum of individuals followed under naturalistic circumstances, systematic reviews of observational studies may offer an added dimension in the evaluation of drug safety that is complementary to that provided by clinical trials.^8,9 Additionally, observational studies may allow researchers to move from the controversial concept of suicidality to hard outcomes such as suicide attempt and completion. Specifically, we set out to quantify the risk of completed or attempted suicide among people in different age groups with depression after exposure to SSRIs.     

School Performance and the Risk of Suicidal Thoughts in Young Adults: Population-Based Study

Although low school performance is related to attempted and completed suicide, its relationship with suicidal thoughts has been less clear. We conducted a population-based study including 10081 individuals aged 18–29 years in Stockholm, Sweden, and found a clear positive gradient in the risk of lifetime suicidal thoughts with decreasing levels of compulsory school leaving grades. This relationship was somewhat attenuated but remained significant in multivariate models accounting for family background, severe adult psychopathology and adult socioeconomic conditions. School failure is associated with an increased risk of experiencing suicidal thoughts and may also increase the tendency of acting upon them.     

NSAID use selectively increases the risk of non-fatal myocardial infarction: a systematic review of randomised trials and observational studies

Background

Recent clinical trials and observational studies have reported increased coronary events associated with non steroidal anti-inflammatory drugs (NSAIDs). There appeared to be a disproportionate increase in non-fatal versus fatal events, however, numbers of fatal events in individual studies were too small, and event rates too low, to be meaningful.

Objectives

We undertook a pooled analysis to investigate the effect of NSAIDs on myocardial infarction (MI) risk with the specific aim to differentiate non-fatal from fatal events.

Methods

We searched Pubmed (January, 1990 to March, 2010) for observational studies and randomised controlled trials that assessed the effect of NSAIDs (traditional or selective COX-2 inhibitors [coxibs]) on MI incidence separately for fatal and non-fatal events. Summary estimates of relative risk (RR) for non-fatal and fatal MIs were calculated with a random effects model.

Results

NSAID therapy carried a RR of 1.30 (95% CI, 1.20–1.41) for non-fatal MI with no effect on fatal MI (RR 1.02, 95% CI, 0.89–1.17) in six observational studies. Overall, the risk increase for non-fatal MI was 25% higher (95% CI, 11%–42%) than for fatal MI. The two studies that included only individuals with prior cardiovascular disease presented risk estimates for non-fatal MI on average 58% greater (95% CI, 26%–98%) than those for fatal MI. In nine randomised controlled trials, all investigating coxibs, the pooled RR estimate for non-fatal MI was 1.61 (95% CI, 1.04–2.50) and 0.86 (95% CI 0.51–1.47) for fatal MIs.

Conclusions

NSAID use increases the risk of non-fatal MI with no substantial effect on fatal events. Such differential effects, with potentially distinct underlying pathology may provide insights into NSAID-induced coronary pathology. We studied the association between the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of myocardial infarction (MI), separating non-fatal from fatal events, summarizing the evidence from both observational studies and randomised controlled trials. An increased risk of non-fatal MI was clearly found in both types of studies while use of NSAID did not confer an increased risk of fatal MI. Our findings provide support for the concept that thrombi generated under NSAID treatment could be different from spontaneous thrombi.     

Deliberate self harm: systematic review of efficacy of psychosocial and pharmacological treatments in preventing repetition

Objective: To identify and synthesise the findings from all randomised controlled trials that have examined the effectiveness of treatments of patients who have deliberately harmed themselves. Design: Systematic review of randomised controlled trials of psychosocial and physical treatments. Studies categorised according to type of treatment. When there was more than one investigation in a particular category a summary odds ratio was estimated with the Mantel-Haenszel method. Setting: Randomised trials available in electronic databases in 1996, in the Cochrane Controlled Trials Register in 1997, and from hand searching of journals to 1997. Subjects: Patients who had deliberately harmed themselves shortly before entry into the trials with information on repetition of behaviour. The included trials comprised 2452 randomised participants with outcome data. Main outcome measure: Repetition of self harm. Results: 20 trials reported repetition of self harm as an outcome variable, classified into 10 categories. Summary odds ratio (all for comparison with standard aftercare) indicated reduced repetition for problem solving therapy (0.73; 95% confidence interval 0.45 to 1.18) and for provision of an emergency contact card in addition to standard care (0.45; 0.19 to 1.07). The summary odds ratios were 0.83 (0.61 to 1.14) for trials of intensive aftercare plus outreach and 1.19 (0.53 to 2.67) for antidepressant treatment compared with placebo. Significantly reduced rates of further self harm were observed for depot flupenthixol versus placebo in multiple repeaters (0.09; 0.02 to 0.50) and for dialectical behaviour therapy versus standard aftercare (0.24; 0.06 to 0.93). Conclusion: There remains considerable uncertainty about which forms of psychosocial and physical treatments of patients who harm themselves are most effective. Further larger trials of treatments are needed.

Key messages

• A systematic review of the effectiveness of psychosocial and drug treatments of patients who deliberately harm themselves identified 20 randomised controlled trials in which repetition of self harm was reported as an outcome
• Promising results were found for problem solving therapy, provision of a card to allow patients to make emergency contact with services, depot flupenthixol for recurrent self harm, and long term psychological therapy for female patients with borderline personality disorder and recurrent self harm
• Assertive outreach can help to keep patients in treatment
• Nearly all the trials included too few patients to detect clinically significant differences in repetition of self harm, and even synthesis of results by meta-analysis did not have the power to detect such differences
• There is an urgent need for large trials of promising therapies for this substantial clinical population

     

Risk of suicide,deliberate self‐harm and psychiatric illness after the loss of a close relative: A nationwide cohort study

The loss of a close relative is a common event, yet it is associated with increased risk of serious mental health conditions. No large‐scale study has explored up to now the importance of the bereaved person's relation to the deceased while accounting for gender and age. We performed a nationwide Danish cohort study using register information from 1995 through 2013 on four sub‐cohorts including all persons aged ≥18 years exposed to the loss of a child, spouse, sibling or parent. We identified 1,445,378 bereaved persons, and each was matched by gender, age and family composition to five non‐bereaved persons. Cumulative incidence proportions were calculated to estimate absolute differences in suicide, deliberate self‐harm and psychiatric illness. Cox proportional hazard regression was used to calculate hazard ratios while adjusting for potential confounders. Results revealed that the risk of suicide, deliberate self‐harm and psychiatric illness was increased in the bereaved cohorts for at least 10 years after the loss, particularly during the first year. During that year, the risk difference was 18.9 events in 1,000 persons after loss of a child (95% CI: 17.6‐20.1) and 16.0 events in 1,000 persons after loss of the spouse (95% CI: 15.4‐16.6). Hazard ratios were generally highest after loss of a child, in younger persons, and after sudden loss by suicide, homicide or accident. One in three persons with a previous psychiatric diagnosis experienced suicide, deliberate self‐harm or psychiatric illness within the first year of bereavement. In conclusion, this study shows that the risk of suicide, deliberate self‐harm and psychiatric illness is high after the loss of a close relative, especially in susceptible subgroups. This suggests the need for early identification of high‐risk persons displaying adjustment problems after loss of a close family member, in order to reduce the risk of serious mental health outcomes.     

Mortality and Suicide Risk in Treatment-Resistant Depression: An Observational Study of the Long-Term Impact of Intervention

Major depressive disorder is a common global disease that causes a significant societal burden. Most interventional studies of depression provide a limited assessment of the interventions on mortality and suicide risks. This study utilizes data from an observational registry of patients with major depressive disorder to determine the impact of intervention (vagus nerve stimulation or standard pharmacological/non-pharmacological therapy) and a latent factor, patient trajectory toward response, on mortality, suicide and suicidal ideation. A total of 636 patients were available for an intent-to-treat analysis of all-cause mortality, suicide and suicidal ideation. Patients treated with vagus nerve stimulation in addition to standard therapies experienced lower, but not statistically significant, all-cause mortality (vagus nerve stimulation 4.93 per 1,000 person-years vs. 10.02 per 1,000 patient years for treatment as usual) and suicide rates (vagus nerve stimulation 0.88 per 1,000 person-years vs. 1.61 per 1,000 patient years for treatment as usual). Treatment with vagus nerve stimulation produced a statistically lower relative risk of suicidal ideation 0.80, 95% confidence interval (0.68,0.95). Further, patients that responded to either treatment saw a 51% reduction in relative risk of suicidal behavior; relative risk and 95% confidence interval of 0.49 (0.41,0.58). In summary, we find that treatment with adjunctive vagus nerve stimulation can potentially lower the risk of all-cause mortality, suicide and suicide attempts.     

Suicidal thought and behavior in high school students in Adana, Turkey

Fifty years ago adolescents mostly died of natural causes, whereas they now die from more preventable causes. Part of this change has been a worldwide rise in adolescent suicide rates in both developed and developing countries. Suicides are probably under reported due to cultural and religious stigma attached to self-destruction. Objectives of this study were to collect data about suicidal thoughts, plans and attempts and related sociodemographic details in high school students. The population comprised 2,480 randomly selected students among 46,271 students from 72 high schools in 1999-2000 in Adana and 2,352 (94.8%) students from 10 schools were reached and given a questionnaire modified using Youth Risk Behavior Survey Questionnaire (YRBSQ). Chi2 and Kolmogorov-Smirnov tests were used. Mean age was 16.5 +/- 1 (14-21) year, 1,187 (50.5%) students reported severe desperation, 526 students (22.4%) had suicidal thoughts, 332 (14.1%) planned committing suicide, 145 (6.2%) attempted suicide. The occurrence rate of desperation, suicidal thoughts, plans, attempts and the mean number of attempts were significantly higher in females than males. Adolescent suicide is a tragedy affecting individual, family, peers, and community. Families, teachers, and physicians should be aware of risk factors for suicide.     

Adolescent suicidal behavior across the excess weight status spectrum

Objective:

Relative suicidal behavioral risks (ideation, attempts) for overweight, obese, and extremely obese adolescents (vs. healthy weight) and who did/did not accurately perceive themselves as overweight were examined in this study.

Design and Methods:

A new variable (weight status/accuracy) was computed that combined actual weight status (based on BMI) with weight perception accuracy. To evaluate the effect of weight status/accuracy on each suicidal risk behavior, logistic regression was performed to calculate odds‐ratios and 95% confidence intervals (CI). Potential model covariates included gender, age, race, survey year, and whether they had felt sad/hopeless.

Results:

Weight perception accuracy increased as the degree of excess weight increased. Relative to healthy weight, being obese or extremely obese (but not overweight) was associated with significantly greater risk for adolescent engagement in suicidal ideation, but was unrelated to suicide attempts. Adolescents in all excess weight categories who were accurate in their weight perception were at significantly greater odds of suicidal ideation, whereas those who were inaccurate were of no greater odds of suicidal ideation than healthy weight youth who accurately perceived their weight. Findings regarding suicide attempts varied based on actual weight/weight perception accuracy and race/ethnicity.

Conclusion:

The present findings are both important and clinically relevant. While widely accepted that there are multiple pathways to suicide, our understanding of adolescent suicidal behavior risks and accordingly, prevention efforts, will be informed by comprehensive prospective studies that should also, from here forward, consider categorization of the entire weight spectrum (e.g., extreme obesity).     

What Interrupts Suicide Attempts in Men: A Qualitative Study

Despite higher rates of suicide in men, there is a dearth of research examining the perspectives and experiences of males at risk of suicide, particularly in terms of understanding how interventions can be tailored to men’s specific needs. The current study aimed to examine factors assisting, complicating or inhibiting interventions for men at risk, as well as outlining the roles of family, friends and others in male suicide prevention. Thirty-five male suicide survivors completed one-to-one interviews, and forty-seven family and friends of male suicide survivors participated in eight focus groups. Thematic analysis revealed five major themes: (1) development of suicidal behaviours tends to follow a common path associated with specific types of risk factors (disrupted mood, unhelpful stoic beliefs and values, avoidant coping strategies, stressors), (2) men at risk of suicide tend to systematically misinterpret changes in their behaviour and thinking, (3) understanding mood and behavioural changes in men enables identification of opportunities to interrupt suicide progression, (4) distraction, provision of practical and emotional supports, along with professional intervention may effectively interrupt acute risk of harm, and (5) suicidal ideation may be reduced through provision of practical help to manage crises, and helping men to focus on obligations and their role within families. Findings suggest that interventions for men at risk of suicidal behaviours need to be tailored to specific risk indicators, developmental factors, care needs and individuals’ preferences. To our knowledge this is the first qualitative study to explore the experiences of both suicidal men and their family/friends after a suicide attempt, with the view to improve understanding of the processes which are effective in interrupting suicide and better inform interventions for men at risk.     

Cross-National Analysis of the Associations among Mental Disorders and Suicidal Behavior: Findings from the WHO World Mental Health Surveys

Background

Suicide is a leading cause of death worldwide. Mental disorders are among the strongest predictors of suicide; however, little is known about which disorders are uniquely predictive of suicidal behavior, the extent to which disorders predict suicide attempts beyond their association with suicidal thoughts, and whether these associations are similar across developed and developing countries. This study was designed to test each of these questions with a focus on nonfatal suicide attempts.

Methods and Findings

Data on the lifetime presence and age-of-onset of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) mental disorders and nonfatal suicidal behaviors were collected via structured face-to-face interviews with 108,664 respondents from 21 countries participating in the WHO World Mental Health Surveys. The results show that each lifetime disorder examined significantly predicts the subsequent first onset of suicide attempt (odds ratios [ORs] = 2.9–8.9). After controlling for comorbidity, these associations decreased substantially (ORs = 1.5–5.6) but remained significant in most cases. Overall, mental disorders were equally predictive in developed and developing countries, with a key difference being that the strongest predictors of suicide attempts in developed countries were mood disorders, whereas in developing countries impulse-control, substance use, and post-traumatic stress disorders were most predictive. Disaggregation of the associations between mental disorders and nonfatal suicide attempts showed that these associations are largely due to disorders predicting the onset of suicidal thoughts rather than predicting progression from thoughts to attempts. In the few instances where mental disorders predicted the transition from suicidal thoughts to attempts, the significant disorders are characterized by anxiety and poor impulse-control. The limitations of this study include the use of retrospective self-reports of lifetime occurrence and age-of-onset of mental disorders and suicidal behaviors, as well as the narrow focus on mental disorders as predictors of nonfatal suicidal behaviors, each of which must be addressed in future studies.

Conclusions

This study found that a wide range of mental disorders increased the odds of experiencing suicide ideation. However, after controlling for psychiatric comorbidity, only disorders characterized by anxiety and poor impulse-control predict which people with suicide ideation act on such thoughts. These findings provide a more fine-grained understanding of the associations between mental disorders and subsequent suicidal behavior than previously available and indicate that mental disorders predict suicidal behaviors similarly in both developed and developing countries. Future research is needed to delineate the mechanisms through which people come to think about suicide and subsequently progress from ideation to attempts. Please see later in the article for Editors'' Summary     

Weight Status,Psychological Health,Suicidal Thoughts,and Suicide Attempts in Dutch Adolescents: Results From the 2003 E‐MOVO Project

This study describes the association between weight status and psychological health, suicidal thoughts and suicide attempts in adolescents from a population‐based study of 21,730 adolescents who responded to a classroom‐based internet questionnaire. It demonstrated clear associations between weight status in adolescents and poor psychological health, suicidal thoughts and suicide attempts, especially in obese individuals. Obese boys and girls were more likely to be classified as “psychologically unhealthy” than were normal weight subjects. They also reported more suicidal thoughts and suicide attempts.     

Psychiatric Diagnoses and Risk of Suicidal Behaviour in Young Disability Pensioners: Prospective Cohort Studies of All 19-23 Year Olds in Sweden in 1995, 2000, and 2005, Respectively

Objective

Increasing rates of disability pension (DP) have been observed among young adults. We studied specific psychiatric DP diagnoses and subsequent risk of suicidal behaviour in a series of three cohorts of young adult in Sweden.

Method

In a nationwide register study, we included all young adults who in 1995, 2000, and 2005, respectively, were 19–23 years old and lived in Sweden (n≈500,000 per cohort). Rates of DP and specific psychiatric DP diagnoses were recorded in each cohort. Hazard ratios (HRs) and 95% confidence intervals (CIs) for suicidal behaviour during the following five years, with the corresponding age group as reference, were calculated by Cox proportional hazard regression, adjusted for demographic variables and previous own and parental suicidal behaviour.

Results

The overall proportion with DP in this age group increased from 0.92% in 1995 to 2.29% in 2005, with particularly large increases in psychiatric diagnoses such as hyperkinetic disorders, pervasive developmental disorders, and depression/anxiety. The overall proportion of young disability pensioners attempting suicide during the five-year follow-up increased from 2.21% in the 1995 cohort to 3.81% in the 2005 cohort. Within most psychiatric DP diagnoses, the risk of attempted suicide did not change significantly over time, whereas suicide attempts increased in the reference group. Accordingly, the HRs for suicide attempt decreased in some psychiatric DP diagnoses. The highest adjusted HRs were observed for depression/anxiety (16.41; CI: 9.06 to 29.74) and schizophrenia (9.37; 6.13 to 14.31) in the 1995 cohort. The rate of suicide among young disability pensioners during follow-up ranged from 0.19% in 1995 to 0.37% in 2005, mainly occurring in individuals with psychiatric diagnoses.

Conclusion

Suicidal behaviour has become more prevalent among young disability pensioners, which co-occurred with an increased tendency to grant DP in psychiatric diagnoses with a known high risk of suicidal behaviour. Preventive measures are warranted.     

Suicidal process,suicidal communication and psychosocial situation of young suicide attempters in a rural Vietnamese community

The study aimed to explore the suicidal process, suicidal communication and psychosocial situation of young suicide attempters in a rural community in Hanoi, Vietnam. Semi-structured interviews were conducted, in a community setting, with 19 suicide attempters aged 15-24 who had been consecutively hospitalized in an intensive care unit. In 12 of 19 cases, the first pressing, distinct and constant suicidal thoughts appeared less than one day before the suicide attempt in question. However, distress and mild, fleeting suicidal thoughts had been present up to six months before the suicide attempt in 16 cases. Five respondents had a suicide plan one to three days before attempting suicide. Altogether, 13 engaged in some form of suicidal communication before their attempt. This communication was, however, difficult for outsiders to interpret. Twelve of the respondents were victims of regular physical abuse and 16 had suffered psychological violence for at least one year before attempting suicide. Eighteen of the respondents used pesticides or raticides in their suicide attempts. None sought advice or consultation in the community despite long-standing psychosocial problems. The strategy of reducing the availability of suicide means (e.g., pesticides or raticides) in Asian countries should be complemented with a long-term suicide-preventive strategy that targets school dropouts and domestic violence, and promotes coping abilities and communication about psychological and social problems as well as recognition of signs of distress and suicidal communication.     

A newly identified group of adolescents at “invisible” risk for psychopathology and suicidal behavior: findings from the SEYLE study

This study explored the prevalence of risk behaviors (excessive alcohol use, illegal drug use, heavy smoking, reduced sleep, overweight, underweight, sedentary behavior, high use of Internet/TV/videogames for reasons not related to school or work, and truancy), and their association with psychopathology and self‐destructive behaviors, in a sample of 12,395 adolescents recruited in randomly selected schools across 11 European countries. Latent class analysis identified three groups of adolescents: a low‐risk group (57.8%) including pupils with low or very low frequency of risk behaviors; a high‐risk group (13.2%) including pupils who scored high on all risk behaviors, and a third group (“invisible” risk, 29%) including pupils who were positive for high use of Internet/TV/videogames for reasons not related to school or work, sedentary behavior and reduced sleep. Pupils in the “invisible” risk group, compared with the high‐risk group, had a similar prevalence of suicidal thoughts (42.2% vs. 44%), anxiety (8% vs. 9.2%), subthreshold depression (33.2% vs. 34%) and depression (13.4% vs. 14.7%). The prevalence of suicide attempts was 5.9% in the “invisible” group, 10.1% in the high‐risk group and 1.7% in the low‐risk group. The prevalence of all risk behaviors increased with age and most of them were significantly more frequent among boys. Girls were significantly more likely to experience internalizing (emotional) psychiatric symptoms. The “invisible” group may represent an important new intervention target group for potentially reducing psychopathology and other untoward outcomes in adolescence, including suicidal behavior.     

Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression.

OBJECTIVE--A comprehensive meta-analysis of clinical trial data was performed to assess the possible association of fluoxetine and suicidality (suicidal acts and ideation). DESIGN--Retrospective analysis of pooled data from 17 double blind clinical trials in patients with major depressive disorder comparing fluoxetine (n = 1765) with a tricyclic antidepressant (n = 731) or placebo (n = 569), or both. MAIN OUTCOME MEASURES--Multiple data sources were searched to identify patients with suicidal acts. Suicidal ideation was assessed with item 3 of the Hamilton depression rating scale, which systematically rates suicidality. Emergence of substantial suicidal ideation was defined as a change in the rating of this item from 0 or 1 at baseline to 3 or 4 during double blind treatment; worsening was defined as any increase from baseline; improvement was defined as a decrease from baseline at the last visit during the treatment. RESULTS--Suicidal acts did not differ significantly in comparisons of fluoxetine with placebo (0.2% v 0.2%, p = 0.494, Mantel-Haenszel adjusted incidence difference) and with tricyclic antidepressants (0.7% v 0.4%, p = 0.419). The pooled incidence of suicidal acts was 0.3% for fluoxetine, 0.2% for placebo, and 0.4% for tricyclic antidepressants, and fluoxetine did not differ significantly from either placebo (p = 0.533, Pearson''s chi 2) or tricyclic antidepressants (p = 0.789). Suicidal ideation emerged marginally significantly less often with fluoxetine than with placebo (0.9% v 2.6%, p = 0.094) and numerically less often than with tricyclic antidepressants (1.7% v 3.6%, p = 0.102). The pooled incidence of emergence of substantial suicidal ideation was 1.2% for fluoxetine, 2.6% for placebo, and 3.6% for tricyclic antidepressants. The incidence was significantly lower with fluoxetine than with placebo (p = 0.042) and tricyclic antidepressants (p = 0.001). Any degree of worsening of suicidal ideation was similar with fluoxetine and placebo (15.4% v 17.9%, p = 0.196) and with fluoxetine and tricyclic antidepressants (15.6% v 16.3%, p = 0.793). The pooled incidence of worsening of suicidal ideation was 15.3% for fluoxetine, 17.9% for placebo, and 16.3% for tricyclic antidepressants. The incidence did not differ significantly with fluoxetine and placebo (p = 0.141) or tricyclic antidepressants (p = 0.542). Suicidal ideation improved significantly more with fluoxetine than with placebo (72.0% v 54.8%, p less than 0.001) and was similar to the improvement with tricyclic antidepressants (72.5% v 69.8%, p = 0.294). The pooled incidence of improvement of suicidal ideation was 72.2% for fluoxetine, 54.8% for placebo, and 69.8% for tricyclic antidepressants. The incidence with fluoxetine was significantly greater than with placebo (p less than 0.001) and did not differ from that with tricyclic antidepressants (p = 0.296). CONCLUSIONS--Data from these trials do not show that fluoxetine is associated with an increased risk of suicidal acts or emergence of substantial suicidal thoughts among depressed patients.     

Drug-induced orthostatic hypotension: A systematic review and meta-analysis of randomised controlled trials

BackgroundDrug-induced orthostatic hypotension (OH) is common, and its resulting cerebral hypoperfusion is linked to adverse outcomes including falls, strokes, cognitive impairment, and increased mortality. The extent to which specific medications are associated with OH remains unclear.Methods and findingsWe conducted a systematic review and meta-analysis to evaluate the extent to which specific drug groups are associated with OH. EMBASE, MEDLINE, and Web of Science databases were searched from inception through 23 November 2020. Placebo-controlled randomised controlled trials (RCTs) on any drug reporting on OH as an adverse effect in adults (≥18 years) were eligible. Three authors extracted data on the drug, OH, dose, participant characteristics, and study setting. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to appraise evidence. Summary odds ratios (ORs) were estimated for OH using fixed effects Mantel–Haenszel statistics. We conducted subgroup analysis on validity of OH measurement, drug dose, risk of bias, age, and comorbidity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to summarise the certainty of evidence. Of 36,940 citations, 69 eligible RCTs were included in the meta-analysis comprising 27,079 participants. Compared with placebo, beta-blockers and tricyclic antidepressants were associated with increased odds of OH (OR 7.76 [95% CI 2.51, 24.03]; OR 6.30 [95% CI 2.86, 13.91]). Alpha-blockers, antipsychotics, and SGLT-2 inhibitors were associated with up to 2-fold increased odds of OH, compared to placebo. There was no statistically significant difference in odds of OH with vasodilators (CCBs, ACE inhibitors/ARBs, SSRIs), compared to placebo. Limitations of this study are as follows: data limited to placebo-controlled studies, (excluding head-to-head trials), many RCTs excluded older participants; therefore results may be amplified in older patients in the clinical setting. The study protocol is publicly available on PROSPERO (CRD42020168697).ConclusionsMedications prescribed for common conditions (including depression, diabetes, and lower urinary tract symptoms) were associated with significantly increased odds of OH. Drugs causing sympathetic inhibition were associated with significantly increased odds of OH, while most vasodilators were associated with small nonsignificant differences in odds of OH, compared to placebo. Drugs targeting multiple parts of the orthostatic blood pressure (BP) reflex pathway (e.g. sympathetic inhibition, vasodilation, cardio-inhibitory effects) may carry cumulative risk, suggesting that individuals with polypharmacy could benefit from postural BP monitoring.

Cini Bhanu and colleagues evaluate the extent to which different drug groups are associated with orthostatic hypertension in this systematic review and meta-analysis.     

Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation

ObjectiveTo examine the benefits and risks of long term anticoagulation (warfarin) compared with antiplatelet treatment (aspirin/indoprofen) in patients with non-rheumatic atrial fibrillation.MethodsMeta-analysis of randomised controlled trials from Cochrane library, Medline, Embase, Cinhal, and Sigle from 1966 to December 1999. Odds ratios (95% confidence intervals) calculated to estimate treatment effects.ResultsNo trials were found from before 1989. There were five randomised controlled trials published between 1989-99. There were no significant differences in mortality between the two treatment options (fixed effects model: odd ratio 0.74 (95% confidence interval 0.39 to 1.40) for stroke deaths; 0.86 (0.63 to 1.17) for vascular deaths). There was a borderline significant difference in non-fatal stroke in favour of anticoagulation (0.68 (0.46 to 0.99)); and 0.75 (0.50 to 1.13) after exclusion of one trial with weak methodological design. A random effects model showed no significant difference in combined fatal and non-fatal events (odds ratio 0.79 (0.61 to 1.02)). There were more major bleeding events among patients on anticoagulation than on antiplatelet treatment (odds ratio 1.45 (0.93 to 2.27)). One trial was stopped prematurely after a significant difference in favour of anticoagulation was observed. The only trial to show a significant difference in effect (favouring anticoagulation) was methodologically weaker in design than the others.ConclusionsThe heterogeneity between the trials and the limited data result in considerable uncertainty about the value of long term anticoagulation compared with antiplatelet treatment. The risks of bleeding and the higher cost of anticoagulation make it an even less convincing treatment option.