Mark Sinyor

Does inclusion of a placebo arm influence response to active antidepressant treatment in randomized controlled trials? Results from pooled and meta-analyses.

OBJECTIVE To determine if the inclusion of a placebo arm and/or the number of active comparators in antidepressant trials influences the response rates of the active medication and/or placebo. DATA SOURCES Searches of MEDLINE, PsycINFO, and pharmaceutical Web sites for published trials or trials conducted but unpublished between January 1996 and October 2007. STUDY SELECTION 2,275 citations were reviewed, 285 studies were retrieved, and 90 were included in the analysis. Trials reporting response and/or remission rates in adult subjects treated with an antidepressant monotherapy for unipolar major depression were included. DATA EXTRACTION The primary investigator recorded the number of responders and/or remitters in the intent-to-treat population of each study arm or computed these numbers using the quoted rates. DATA SYNTHESIS Poisson regression analyses demonstrated that mean response rate for the active medication was higher in studies comparing 2 or more active medications without a placebo arm than in studies comparing 2 or more active medications with a placebo arm (65.4% vs 57.7%, P < .0001) or in studies comparing only 1 active medication with placebo (65.4% vs 51.7%, P = .0005). Mean response rate for placebo was significantly lower in studies comparing 1 rather than 2 or more active medications (34.3% vs 44.6%, P = .003). Mean remission rates followed a similar pattern. Meta-analysis confirmed results from the pooled analysis. CONCLUSIONS These data suggest that antidepressant response rates in randomized control trials may be influenced by the presence of a placebo arm and by the number of treatment arms and that placebo response rates may be influenced by the number of active treatment arms in a study.

International Society for Bipolar Disorders Task Force on Suicide: meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder.

Bipolar disorder is associated with a high risk of suicide attempts and suicide death. The main objective of the present study was to identify and quantify the demographic and clinical correlates of attempted and completed suicide in people with bipolar disorder.

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. Design Natural experiment. Setting City of Toronto and province of Ontario, Canada; records at the chief coroner’s office of Ontario 1993-2001 (nine years before the barrier) and July 2003-June 2007 (four years after the barrier). Participants 14 789 people who completed suicide in the city of Toronto and in Ontario. Main outcome measure Changes in yearly rates of suicide by jumping at Bloor Street Viaduct, other bridges, and buildings, and by other means. Results Yearly rates of suicide by jumping in Toronto remained unchanged between the periods before and after the construction of a barrier at Bloor Street Viaduct (56.4 v 56.6, P=0.95). A mean of 9.3 suicides occurred annually at Bloor Street Viaduct before the barrier and none after the barrier (P<0.01). Yearly rates of suicide by jumping from other bridges and buildings were higher in the period after the barrier although only significant for other bridges (other bridges: 8.7 v 14.2, P=0.01; buildings: 38.5 v 42.7, P=0.32). Conclusions Although the barrier prevented suicides at Bloor Street Viaduct, the rate of suicide by jumping in Toronto remained unchanged. This lack of change might have been due to a reciprocal increase in suicides from other bridges and buildings. This finding suggests that Bloor Street Viaduct may not have been a uniquely attractive location for suicide and that barriers on bridges may not alter absolute rates of suicide by jumping when comparable bridges are nearby.

A review of factors associated with greater likelihood of suicide attempts and suicide deaths in bipolar disorder: Part II of a report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder

Objectives: Many factors influence the likelihood of suicide attempts or deaths in persons with bipolar disorder. One key aim of the International Society for Bipolar Disorders Task Force on Suicide was to summarize the available literature on the presence and magnitude of effect of these factors. Methods: A systematic review of studies published from 1 January 1980 to 30 May 2014 identified using keywords ‘bipolar disorder’ and ‘suicide attempts or suicide’. This specific paper examined all reports on factors putatively associated with suicide attempts or suicide deaths in bipolar disorder samples. Factors were subcategorized into: (1) sociodemographics, (2) clinical characteristics of bipolar disorder, (3) comorbidities, and (4) other clinical variables. Results: We identified 141 studies that examined how 20 specific factors influenced the likelihood of suicide attempts or deaths. While the level of evidence and degree of confluence varied across factors, there was at least one study that found an effect for each of the following factors: sex, age, race, marital status, religious affiliation, age of illness onset, duration of illness, bipolar disorder subtype, polarity of first episode, polarity of current/recent episode, predominant polarity, mood episode characteristics, psychosis, psychiatric comorbidity, personality characteristics, sexual dysfunction, first-degree family history of suicide or mood disorders, past suicide attempts, early life trauma, and psychosocial precipitants. Conclusion: There is a wealth of data on factors that influence the likelihood of suicide attempts and suicide deaths in people with bipolar disorder. Given the heterogeneity of study samples and designs, further research is needed to replicate and determine the magnitude of effect of most of these factors. This approach can ultimately lead to enhanced risk stratification for patients with bipolar disorder.

Epidemiology, neurobiology and pharmacological interventions related to suicide deaths and suicide attempts in bipolar disorder: Part I of a report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder

Objectives: Bipolar disorder is associated with elevated risk of suicide attempts and deaths. Key aims of the International Society for Bipolar Disorders Task Force on Suicide included examining the extant literature on epidemiology, neurobiology and pharmacotherapy related to suicide attempts and deaths in bipolar disorder. Methods: Systematic review of studies from 1 January 1980 to 30 May 2014 examining suicide attempts or deaths in bipolar disorder, with a specific focus on the incidence and characterization of suicide attempts and deaths, genetic and non-genetic biological studies and pharmacotherapy studies specific to bipolar disorder. We conducted pooled, weighted analyses of suicide rates. Results: The pooled suicide rate in bipolar disorder is 164 per 100,000 person-years (95% confidence interval = [5, 324]). Sex-specific data on suicide rates identified a 1.7:1 ratio in men compared to women. People with bipolar disorder account for 3.4–14% of all suicide deaths, with self-poisoning and hanging being the most common methods. Epidemiological studies report that 23–26% of people with bipolar disorder attempt suicide, with higher rates in clinical samples. There are numerous genetic associations with suicide attempts and deaths in bipolar disorder, but few replication studies. Data on treatment with lithium or anticonvulsants are strongly suggestive for prevention of suicide attempts and deaths, but additional data are required before relative anti-suicide effects can be confirmed. There were limited data on potential anti-suicide effects of treatment with antipsychotics or antidepressants. Conclusion: This analysis identified a lower estimated suicide rate in bipolar disorder than what was previously published. Understanding the overall risk of suicide deaths and attempts, and the most common methods, are important building blocks to greater awareness and improved interventions for suicide prevention in bipolar disorder. Replication of genetic findings and stronger prospective data on treatment options are required before more decisive conclusions can be made regarding the neurobiology and specific treatment of suicide risk in bipolar disorder.

Characterizing Suicide in Toronto: An Observational Study and Cluster Analysis

Objective: To determine whether people who have died from suicide in a large epidemiologic sample form clusters based on demographic, clinical, and psychosocial factors. Method: We conducted a coroners chart review for 2886 people who died in Toronto, Ontario, from 1998 to 2010, and whose death was ruled as suicide by the Office of the Chief Coroner of Ontario. A cluster analysis using known suicide risk factors was performed to determine whether suicide deaths separate into distinct groups. Clusters were compared according to person- and suicide-specific factors. Results: Five clusters emerged. Cluster 1 had the highest proportion of females and nonviolent methods, and all had depression and a past suicide attempt. Cluster 2 had the highest proportion of people with a recent stressor and violent suicide methods, and all were married. Cluster 3 had mostly males between the ages of 20 and 64, and all had either experienced recent stressors, suffered from mental illness, or had a history of substance abuse. Cluster 4 had the youngest people and the highest proportion of deaths by jumping from height, few were married, and nearly one-half had bipolar disorder or schizophrenia. Cluster 5 had all unmarried people with no prior suicide attempts, and were the least likely to have an identified mental illness and most likely to leave a suicide note. Conclusions: People who die from suicide assort into different patterns of demographic, clinical, and death-specific characteristics. Identifying and studying subgroups of suicides may advance our understanding of the heterogeneous nature of suicide and help to inform development of more targeted suicide prevention strategies.

Association of weekly suicide rates with temperature anomalies in two different climate types

Annual suicide deaths outnumber the total deaths from homicide and war combined. Suicide is a complex behavioral endpoint, and a simple cause-and-effect model seems highly unlikely, but relationships with weather could yield important insight into the biopsychosocial mechanisms involved in suicide deaths. This study has been designed to test for a relationship between air temperature and suicide frequency that is consistent enough to offer some predictive abilities. Weekly suicide death totals and anomalies from Toronto, Ontario, Canada (1986–2009) and Jackson, Mississippi, USA (1980–2006) are analyzed for relationships by using temperature anomaly data and a distributed lag nonlinear model. For both analysis methods, anomalously cool weeks show low probabilities of experiencing high-end suicide totals while warmer weeks are more likely to experience high-end suicide totals. This result is consistent for Toronto and Jackson. Weekly suicide totals demonstrate a sufficient association with temperature anomalies to allow some prediction of weeks with or without increased suicide frequency. While this finding alone is unlikely to have immediate clinical implications, these results are an important step toward clarifying the biopsychosocial mechanisms of suicidal behavior through a more nuanced understanding of the relationship between temperature and suicide.

Substances used in completed suicide by overdose in Toronto: an observational study of coroner's data.

Objective: To identify the substances used by people who die from suicide by overdose in Toronto and to determine the correlates of specific categories of substances used. Method: Coroners records for all cases of suicide by overdose in Toronto, Ontario, during a 10-year period (1998 to 2007) were examined. Data collected included demographic data, all substances detected, and those determined by the coroner to have caused death. Logistic regression analyses were used to examine demographic and clinical factors associated with suicide by different drug types. Results: There were 397 documented suicides by overdose (mean age 49.1 years, 50% female). Most substances detected were psychotropic prescription medications (n = 245), followed by other prescription medications (n = 143) and over-the-counter (OTC) medications (n = 83). More than one-half of all suicides by overdose were determined to have only one specifc substance as the cause of death (n = 206). In suicides where only one class of substance was present in lethal amounts, OTC medication (n = 48), opioid analgesics (n = 44), and tricyclic antidepressants (n = 44) were most common. Conclusions: Suicides by overdose involved the use of different classes of substances, including psychotropic prescription medication, other prescription medications, as well as OTC medications. Physicians and pharmacists should be aware of commonly used prescription and OTC medications in overdose and exercise increased vigilance in prescribing or dispensing them to at-risk patients.

Global trends in suicide epidemiology

Purpose of review Suicide is a major cause of mortality accounting for nearly 1 million deaths globally per year. Suicide occurs throughout the lifespan; therefore, large epidemiological samples are needed to identify patterns in suicide death. This review examines emerging evidence relating to risk and protective factors as well as preventive measures for suicide. Recent findings The global financial crisis, natural disasters, air pollution and second-hand smoke have all been associated with increased suicide rates. At an individual level, past self-harm, parental loss or separation and younger age relative to classmates all confer risk. There is mixed evidence for religious affiliation and lithium levels in drinking water as protective factors. Means restriction strategies including barriers at suicide hotspots, firearms restrictions and limiting access to both pesticides and charcoal have all prevented suicide. Other interventions with recent evidence include improvements in mental health systems, selective serotonin reuptake inhibitor (SSRI) and lithium treatment in youth and mental health awareness in schools. Summary The evidence for risk/protective factors for suicide continues to grow and, more importantly, numerous prevention efforts continue to demonstrate positive outcomes. Public policy experts should attend to the environmental and social determinants of health when devising suicide prevention programs, and the evidence-based prevention strategies identified here should be implemented more broadly.

Suicide in Schizophrenia: An Observational Study of Coroner Records in Toronto

OBJECTIVE Suicide is an important cause of premature mortality in people suffering from schizophrenia. This study aimed to identify demographic, personal, and suicide-specific features that distinguish suicide in people with schizophrenia from those with another severe mental illness (bipolar disorder) and those with neither illness. METHOD We conducted a coroners chart review for 2,886 suicide victims in Toronto from 1998 to 2010. Diagnoses were made based on coroner interviews with available informants including family members, acquaintances, the deceaseds physician(s) and/or review of medical records. Of the total, 258 formed what we defined as the schizophrenia group (204 schizophrenia, 34 unspecified psychotic illness, and 20 schizoaffective disorder). Of the remainder, 169 had bipolar disorder, and 2,459 had neither illness. One-way analysis of variance (ANOVA) tests and χ² tests were conducted to examine differences between the groups. RESULTS The group with schizophrenia was the youngest (mean age for schizophrenia, 41.0 years; bipolar disorder, 43.3 years; and neither, 47.7 years; P < .001), most likely to have never been married (schizophrenia, 75.6%; bipolar disorder, 57.4%; and neither, 52.9%; P < .001), most likely to be living in temporary/assisted housing or jail (schizophrenia, 9.3%; bipolar disorder, 5.4%; and neither, 3.2%; P < .001), and least likely to have experienced a recent stressor (schizophrenia, 26.7%; bipolar disorder, 37.9%; and neither, 54.1%; P < .001). The schizophrenia group was the most likely to use a violent cause of death, specifically by fall from a height or by jumping in front of a vehicle (schizophrenia, 81.4%; bipolar disorder, 58.0%; and neither, 73.1%; P < .001). CONCLUSIONS There are important demographic and suicide-related differences between suicide victims with and without schizophrenia. Notably, suicide in schizophrenia overall appears to be more illness driven and occurs by more violent means than in the bipolar disorder group or those with neither illness.