Legal provisions on medical aid in dying encode moral intuition.

In recent decades, many jurisdictions have moved toward legalizing euthanasia and assisted suicide, alongside a near-universal increase in public acceptance of medical aid in dying. Here, we draw on a comprehensive quantitative review of current laws on assisted dying, experimental survey evidence, and four decades of time-series data to explore the relationship between these legislative transitions and change in moral attitudes. Our analyses reveal that existing laws on medical aid in dying impose a common set of eligibility restrictions, based on the patient's age, decision-making capacity, prognosis, and the nature of their illness. Fulfillment of these eligibility criteria elevates public moral approval of physician-assisted death, equally in countries with (i.e., Spain) and without (i.e., the United Kingdom) assisted dying laws. Finally, historical records of public attitudes toward euthanasia across numerous countries uncovered anticipatory growth in moral approval leading up to legalization, but no accelerated growth thereafter. Taken together, our findings suggest that the enactment of medical aid in dying laws, and their specific provisions, crystallize patterns in moral intuition.

Reevaluating the "deaths of despair" narrative: Racial/ethnic heterogeneity in the trend of psychological distress-related death.

Despite the significant scientific advancement in deciphering the "deaths of despair" narrative, most relevant studies have focused on drug-, alcohol-, and suicide-related (DAS) deaths. This study directly investigated despair as a determinant of death and the temporal variation and racial heterogeneity among individuals. We used psychological distress (PD) as a proxy for despair and drew data from the US National Health Interview Survey-Linked Mortality Files 1997 to 2014, CDC (Centers for Disease Control and Prevention) Multiple Cause of Death database 1997 to 2014, CDC bridged-race population files 1997 to 2014, Current Population Survey 1997 to 1999, and the American Community Survey 2000 to 2014. We used Cox proportional hazards models to estimate mortality hazard ratios of PD and compared age-standardized PD- and DAS-related mortality rates by race/ethnicity and over time. We found that while Whites had a lower prevalence of PD than Blacks and Hispanics throughout the whole period, they underwent distinctive increases in PD-related death and have had a higher PD-related mortality rate than Blacks and Hispanics since the early 2000s. This was predominantly due to Whites' relatively high and increasing vulnerability to PD less the prevalence of PD. Furthermore, PD induced a more pervasive mortality consequence than DAS combined for Whites and Blacks. In addition, PD- and DAS-related deaths displayed a concordant trend among Whites but divergent patterns for Blacks and Hispanics. These findings suggest that 1) DAS-related deaths underestimated the mortality consequence of despair for Whites and Blacks but overestimated it for Hispanics; and 2) despair partially contributed to the DAS trend among Whites but probably not for Blacks and Hispanics.

Mapping the timescale of suicidal thinking.

This study aims to identify the timescale of suicidal thinking, leveraging real-time monitoring data and a number of different analytic approaches. Participants were 105 adults with past week suicidal thoughts who completed a 42-d real-time monitoring study (total number of observations = 20,255). Participants completed two forms of real-time assessments: traditional real-time assessments (spaced hours apart each day) and high-frequency assessments (spaced 10 min apart over 1 h). We found that suicidal thinking changes rapidly. Both descriptive statistics and Markov-switching models indicated that elevated states of suicidal thinking lasted on average 1 to 3 h. Individuals exhibited heterogeneity in how often and for how long they reported elevated suicidal thinking, and our analyses suggest that different aspects of suicidal thinking operated on different timescales. Continuous-time autoregressive models suggest that current suicidal intent is predictive of future intent levels for 2 to 3 h, while current suicidal desire is predictive of future suicidal desire levels for 20 h. Multiple models found that elevated suicidal intent has on average shorter duration than elevated suicidal desire. Finally, inferences about the within-person dynamics of suicidal thinking on the basis of statistical modeling were shown to depend on the frequency at which data was sampled. For example, traditional real-time assessments estimated the duration of severe suicidal states of suicidal desire as 9.5 h, whereas the high-frequency assessments shifted the estimated duration to 1.4 h.

Differential spatial-social accessibility to mental health care and suicide.

In recent years, the United States has been experiencing historically high suicide rates. In the face of mental health care provider shortages that leave millions needing to travel longer to find providers with schedule openings, if any are available at all, the inaccessibility of mental health care has become increasingly central in explaining suicidality. To examine the relationship between access to care and suicide, we leverage a dataset mapping all licensed US psychiatrists and psychotherapists (N= 711,214), as of early 2020, and employ real-world transportation data to model patients' mobility barriers. We find a strong association between reduced mental health care provider spatial-social accessibility and heightened suicide risk. Using a machine learning approach to condition on a host of 22 contextual factors known to be implicated in suicide (e.g., race, education, divorce, gun shop prevalence), we find that in locales where individuals seeking care can access fewer mental health care providers, already more likely to be saturated by demand, suicide risk is increased (3.2% for each reduced SD of psychiatrist accessibility; 2.3% for psychotherapists). Additionally, we observe that local spatial-social accessibility inequalities are associated with further heightened risk of suicide, underscoring the need for research to account for the highly localized barriers preventing many Americans from accessing needed mental health services.

Air pollution and suicide in rural and urban America: Evidence from wildfire smoke.

Air pollution poses well-established risks to physical health, but little is known about its effects on mental health. We study the relationship between wildfire smoke exposure and suicide risk in the United States in 2007 to 2019 using data on all deaths by suicide and satellite-based measures of wildfire smoke and ambient fine particulate matter (PM2.5) concentrations. We identify the causal effects of wildfire smoke pollution on suicide by relating year-over-year fluctuations in county-level monthly smoke exposure to fluctuations in suicide rates and compare the effects across local areas and demographic groups that differ considerably in their baseline suicide risk. In rural counties, an additional day of smoke increases monthly mean PM2.5 by 0.41 µg/m3 and suicide deaths by 0.11 per million residents, such that a 1-µg/m3 (13%) increase in monthly wildfire-derived fine particulate matter leads to 0.27 additional suicide deaths per million residents (a 2.0% increase). These effects are concentrated among demographic groups with both high baseline suicide risk and high exposure to outdoor air: men, working-age adults, non-Hispanic Whites, and adults with no college education. By contrast, we find no evidence that smoke pollution increases suicide risk among any urban demographic group. This study provides large-scale evidence that air pollution elevates the risk of suicide, disproportionately so among rural populations.

Fostering Psychological Safety and Supporting Mental Health Among Cardiovascular Health Care Workers: A Science Advisory From the American Heart Association.

The psychological safety of health care workers is an important but often overlooked aspect of the rising rates of burnout and workforce shortages. In addition, mental health conditions are prevalent among health care workers, but the associated stigma is a significant barrier to accessing adequate care. More efforts are therefore needed to foster health care work environments that are safe and supportive of self-care. The purpose of this brief document is to promote a culture of psychological safety in health care organizations. We review ways in which organizations can create a psychologically safe workplace, the benefits of a psychologically safe workplace, and strategies to promote mental health and reduce suicide risk.

Identifying suicide attempter in major depressive disorder through machine learning: the importance of pain avoidance, event-related potential features of affective processing.

How to achieve a high-precision suicide attempt classifier based on the three-dimensional psychological pain model is a valuable issue in suicide research. The aim of the present study is to explore the importance of pain avoidance and its related neural features in suicide attempt classification models among patients with major depressive disorder. By recursive feature elimination with cross-validation and support-vector-machine algorithms, scores from the measurements and the task-based EEG signals were chosen to achieve a suicide attempt classification model. In the multimodal suicide attempt classifier with an accuracy of 83.91% and an area under the curve of 0.90, pain avoidance ranked as the top one in the optimal feature set. Theta (reward positive feedback minus neutral positive feedback) was the shared neural representation ranking as the top one of event-related potential features in pain avoidance and suicide attempt classifiers. In conclusion, the suicide attempt classifier based on pain avoidance and its related affective processing neural features has excellent accuracy among patients with major depressive disorder. Pain avoidance is a stable and strong indicator for identifying suicide risks in both traditional analyses and machine-learning approaches. A novel methodology is needed to clarify the relationship between cognitive and affective processing evoked by punishment stimuli and pain avoidance.

Suicide gene-enabled cell therapy: A novel approach to scalable human pluripotent stem cell quality control.

There are an increasing number of cell therapy approaches being studied and employed world-wide. An emerging area in this field is the use of human pluripotent stem cell (hPSC) products for the treatment of injuries/diseases that cannot be effectively managed through current approaches. However, as with any cell therapy, vast numbers of functional and safe cells are required. Bioreactors provide an attractive avenue to generate clinically relevant cell numbers with decreased labour and decreased batch to batch variation. Yet, current methods of performing quality control are not readily scalable to the cell densities produced during bioreactor scale-up. One potential solution is the application of inducible/controllable suicide genes that can trigger cell death in unwanted cell types. These types of approaches have been demonstrated to increase the quality and safety of the resultant cell products. In this review, we will provide background on these approaches and how they could be used together with bioreactor technology to create effective bioprocesses for the generation of high quality and safe hPSCs for use in regenerative medicine approaches.

Prolactin-Releasing Peptide Contributes to Stress-Related Mood Disorders and Inhibits Sleep/Mood Regulatory Melanin-Concentrating Hormone Neurons in Rats.

Stress disorders impair sleep and quality of life; however, their pathomechanisms are unknown. Prolactin-releasing peptide (PrRP) is a stress mediator; we therefore hypothesized that PrRP may be involved in the development of stress disorders. PrRP is produced by the medullary A1/A2 noradrenaline (NA) cells, which transmit stress signals to forebrain centers, and by non-NA cells in the hypothalamic dorsomedial nucleus. We found in male rats that both PrRP and PrRP-NA cells innervate melanin-concentrating hormone (MCH) producing neurons in the dorsolateral hypothalamus (DLH). These cells serve as a key hub for regulating sleep and affective states. Ex vivo, PrRP hyperpolarized MCH neurons and further increased the hyperpolarization caused by NA. Following sleep deprivation, intracerebroventricular PrRP injection reduced the number of REM sleep-active MCH cells. PrRP expression in the dorsomedial nucleus was upregulated by sleep deprivation, while downregulated by REM sleep rebound. Both in learned helplessness paradigm and after peripheral inflammation, impaired coping with sustained stress was associated with (1) overactivation of PrRP cells, (2) PrRP protein and receptor depletion in the DLH, and (3) dysregulation of MCH expression. Exposure to stress in the PrRP-insensitive period led to increased passive coping with stress. Normal PrRP signaling, therefore, seems to protect animals against stress-related disorders. PrRP signaling in the DLH is an important component of the PrRP's action, which may be mediated by MCH neurons. Moreover, PrRP receptors were downregulated in the DLH of human suicidal victims. As stress-related mental disorders are the leading cause of suicide, our findings may have particular translational relevance.SIGNIFICANCE STATEMENT Treatment resistance to monoaminergic antidepressants is a major problem. Neuropeptides that modulate the central monoaminergic signaling are promising targets for developing alternative therapeutic strategies. We found that stress-responsive prolactin-releasing peptide (PrRP) cells innervated melanin-concentrating hormone (MCH) neurons that are crucial in the regulation of sleep and mood. PrRP inhibited MCH cell activity and enhanced the inhibitory effect evoked by noradrenaline, a classic monoamine, on MCH neurons. We observed that impaired PrRP signaling led to failure in coping with chronic/repeated stress and was associated with altered MCH expression. We found alterations of the PrRP system also in suicidal human subjects. PrRP dysfunction may underlie stress disorders, and fine-tuning MCH activity by PrRP may be an important part of the mechanism.

Association Between Rapid Opioid Reduction or Discontinuation and Self-Harm, Suicide Attempt, and Suicide Death Among High-Dose Long-Term Opioid Therapy Patients in North Carolina, 2006-2018.

We examined the association between rapid opioid reduction or discontinuation and self-harm, suicide attempt, and suicide death among high-dose long-term opioid therapy (HD-LTOT) patient and examined effect measure modification by individual and neighborhood-level characteristics. Using private insurance data from North Carolina, this retrospective cohort study covered January 2006 to September 2018, with up to four years of follow-up. Participants included patients aged 18-64 years who were prescribed HD-LTOT. Time-varying exposure was ever exposed to rapid opioid reduction or discontinuation vs never exposed. The outcomes were self-harm or suicide attempt, suicide death, and the combined outcome. We estimated cumulative incidence and used Fine-Gray models to estimate sub-distribution hazard ratios (HRs). There were 21,450 HD-LTOT patients. In year 1, rapid opioid reduction or discontinuation was not associated with the combined outcome, HR: 1.09 (95% CI: 0.61-1.96). However, in years 2-4, rapid opioid reduction or discontinuation was associated with higher hazard of the combined outcome, HR: 2.77 (95% CI: 1.45-5.27). This association was stronger among patients with mental health conditions and those residing in underserved neighborhoods. These findings underscore the importance of provider training in adhering to guideline-concordant gradual tapering, offering mental health support, and ensuring patient safety throughout the tapering process.

Suicide Deaths Involving Opioid Poisoning in the United States by Sex, 1999 - 2021.

Suicide remains a leading cause of death in the United States, and recent data suggests that suicide deaths involving opioids are increasing. Given unprecedented increases in drug poisoning deaths, suicidality, and suicide deaths in recent years, an updated examination of the trends in suicide deaths involving opioids is warranted. In this descriptive epidemiologic analysis, we leverage final and provisional mortality data from CDC WONDER to examine trends in suicide deaths involving opioid poisoning from 1999 - 2021 by biological sex. Results reveal complex changes over time: the number and age-adjusted rate of suicide deaths involving opioid poisoning among male and female residents tended to track together, and both increased through 2010, but then diverged with the number and rate of suicide deaths involving opioid poisoning among female residents outpacing that of male residents. However, the number and rate of suicide deaths involving opioid poisoning among male residents then began to stabilize, while that of female residents declined, closing the sex-based gap. Across all years of data, the proportion of suicide deaths that involved opioid poisoning was consistently higher among female decedents (5.8% - 11.0%) compared to male decedents (1.4% - 2.8%). Findings have implications for improved suicide prevention and harm reduction efforts.

Suicide Mortality Among Formerly Incarcerated People Compared With the General Population in North Carolina, 2000-2020.

We aimed to compare rates and characteristics of suicide mortality in formerly incarcerated people with those of the general population in North Carolina. We conducted a retrospective cohort study of 266,400 people released from North Carolina state prisons between January 1, 2000, and March 1, 2020. Using direct and indirect standardization by age, sex, and calendar year, we calculated standardized suicide mortality rates and standardized mortality ratios comparing formerly incarcerated people with the North Carolina general population. We evaluated effect modification by race/ethnicity, sex, age, and firearm involvement. Formerly incarcerated people had approximately twice the overall suicide mortality of the general population for 3 years after release, with the highest rate of suicide mortality being observed in the 2-week period after release. In contrast to patterns in the general population, formerly incarcerated people had higher rates of non-firearm-involved suicide mortality than firearm-involved suicide mortality. Formerly incarcerated female, White and Hispanic/Latino, and emerging adult people had a greater elevation of suicide mortality than their general-population peers compared with other groups. These findings suggest a need for long-term support for formerly incarcerated people as they return to community living and a need to identify opportunities for interventions that reduce the harms of incarceration for especially vulnerable groups. This article is part of a Special Collection on Mental Health.

Geographic Variation, Economic Activity, and Labor Market Characteristics in Trajectories of Suicide in the United States, 2008-2020.

Suicide rates in the United States have increased over the past 15 years, with substantial geographic variation in these increases; yet there have been few attempts to cluster counties by the magnitude of suicide rate changes according to intercept and slope or to identify the economic precursors of increases. We used vital statistics data and growth mixture models to identify clusters of counties by their magnitude of suicide growth from 2008 to 2020 and examined associations with county economic and labor indices. Our models identified 5 clusters, each differentiated by intercept and slope magnitude, with the highest-rate cluster (4% of counties) being observed mainly in sparsely populated areas in the West and Alaska, starting the time series at 25.4 suicides per 100,000 population, and exhibiting the steepest increase in slope (0.69/100,000/year). There was no cluster for which the suicide rate was stable or declining. Counties in the highest-rate cluster were more likely to have agricultural and service economies and less likely to have urban professional economies. Given the increased burden of suicide, with no clusters of counties improving over time, additional policy and prevention efforts are needed, particularly targeted at rural areas in the West.

Invited commentary: unveiling the grim reality-suicide mortality among formerly incarcerated individuals in North Carolina.

In the article by Fitch et al. (Am J Epidemiol 2024;193(3):489-499), the authors highlight the concerning prevalence of suicide mortality among formerly incarcerated individuals in North Carolina. Their retrospective study reveals a doubled suicide risk postrelease, with notable disparities among demographic groups. Urgent interventions are needed, including comprehensive reentry programs and systemic reforms to address structural inequalities. I suggest tailored support services to mitigate suicide risks and promote successful community reintegration, advocating for equity, justice, and human dignity in postrelease efforts.

An introduction to bayesian spatial smoothing methods for disease mapping: modeling county firearm suicide mortality rates.

This article introduces bayesian spatial smoothing models for disease mapping-a specific application of small area estimation where the full universe of data is known-to a wider audience of public health professionals using firearm suicide as a motivating example. Besag, York, and Mollié (BYM) Poisson spatial and space-time smoothing models were fitted to firearm suicide counts for the years 2014-2018. County raw death rates in 2018 ranged from 0 to 24.81 deaths per 10 000 people. However, the highest mortality rate was highly unstable, based on only 2 deaths in a population of approximately 800, and 80.5% of contiguous US counties experienced fewer than 10 firearm suicide deaths and were thus suppressed. Spatially smoothed county firearm suicide mortality estimates ranged from 0.06 to 4.05 deaths per 10 000 people and could be reported for all counties. The space-time smoothing model produced similar estimates with narrower credible intervals as it allowed counties to gain precision from adjacent neighbors and their own counts in adjacent years. bayesian spatial smoothing methods are a useful tool for evaluating spatial health disparities in small geographies where small numbers can result in highly variable rate estimates, and new estimation techniques in R software have made fitting these models more accessible to researchers.

Prognosis and risk of suicide after cancer diagnosis.

INTRODUCTION: Suicide rates are elevated after cancer diagnosis. Existential distress caused by awareness of one's impending death is well-described in patients with cancer. The authors hypothesized that suicide risk is associated with cancer prognosis, and the impact of prognosis on suicide risk is greatest for populations with higher baseline suicide risk. METHODS: The authors identified patients (≥16 years old) with newly diagnosed cancers from 2000 to 2019 in the Surveillance, Epidemiology, and End Results database, representing 27% of US cancers. Multiple primary-standardized mortality ratios (SMR) were used to estimate the relative risk of suicide within 6 months of diagnosis compared to the general US population, adjusted for age, sex, race, and year of follow-up. Suicide rates by 20 most common cancer sites were compared with respective 2-year overall survival rates (i.e., prognosis) using a weighted linear regression model. RESULTS: Among 6,754,704 persons diagnosed with cancer, there were 1610 suicide deaths within 6 months of diagnosis, three times higher than the general population (SMR = 3.1; 95% confidence interval, 3.0-3.3). Suicide risk by cancer site was closely associated with overall prognosis (9.5%/percent survival deficit, R2  = 0.88, p < .0001). The association of prognosis with suicide risk became attenuated over time. For men, the risk of suicide increased by 2.8 suicide deaths per 100,000 person-years (p < .0001) versus 0.3 in women (p < .0001). The risk was also higher for persons ≥60 old and for the White (vs. Black) race. CONCLUSIONS: Poorer prognosis was closely associated with suicide risk early after cancer diagnosis and had a greater effect on populations with higher baseline risks of suicide. This model highlights the need for enhanced psychiatric surveillance and continued research in this patient population.

Transitional photoperiod induces a mania-like behavior in male mice.

This study aimed to investigate the behavioral responses and circadian rhythms of mice to both rapid and gradual increases in photoperiod, mimicking the transition from winter to summer, which is associated with a heightened prevalence of hospitalizations for mania and suicidal behavior. Behavioral tests were performed in C57BL/6 male mice exposed to a transitional photoperiod, from short to long durations. To determine if circadian rhythms are affected, we measured spontaneous locomotor activity and body temperature. Mice exhibited heightened exploratory and risk-taking behaviors compared with equatorial and static long (16:8 h of light-dark cycle for several days) groups. These behaviors were prevented by lithium. Spontaneous locomotor activity and body temperature rhythms persisted and were effectively synchronized; however, the relative amplitude of activity and interdaily stability were diminished. Additionally, the animals displayed increased activity during the light phase. Photoperiodic transition modulates behavior and circadian rhythms, mirroring certain features observed in bipolar disorder patients. This study introduces an animal model for investigating mania-like behavior induced by photoperiodic changes, offering potential insights for suicide prevention strategies and the management of mood disorders.

A systematic review of lethal means safety counseling interventions: impacts on safety behaviors and self-directed violence.

For lethal means safety counseling (LMSC) interventions to reduce population-level suicide rates, interventions must be deployed across many settings and populations. We conducted a systematic search in 6 databases to review the current state of LMSC interventions across study designs, settings, intervention providers, populations, and injury prevention levels (eg, universal). Eligibility criteria were as follows: any individual or group receiving an LMSC intervention involving a human-to-human component aiming to influence adult behaviors related to lethal suicide methods, and outcome assessment of storage behaviors and/or suicidal self-directed violence (SDV). Risk of bias was assessed using the Effective Public Health Practice Project quality assessment tool. A descriptive synthesis approach was used for analysis. Twenty-two studies were included that reported medication- and/or firearm-storage behaviors and/or SDV after LMSC. Of the 19 studies assessing behavioral change, 14 reported a significant improvement in safe storage behaviors, and all studies measuring acceptability reported that participants found the interventions favorable. The quality of evidence was limited. No studies were rated low risk of bias, and 77% were rated high risk of bias. There was substantial heterogeneity in the settings, populations, injury prevention levels, delivery methods, and intervention elements. Many included studies focused on caregivers of pediatric populations, and few studies assessed SDV outcomes. Higher-quality trials conducted across a variety of settings, particularly those focusing on adults at risk of suicide, are needed. This review was preregistered with the International Prospective Register of Systematic Reviews (no. CRD42021230668).

Risk of suicide after hospitalizations due to acute physical health conditions-a cohort study of the Norwegian population.

BACKGROUND: It is well known that individuals recently discharged from psychiatric inpatient care face a high risk of suicide. Severe physical health conditions have also been linked to suicide risk. The risk of suicide following discharge from somatic hospitals is not known for individuals admitted due to acute physical health conditions. METHODS: A Cohort study using data from the entire Norwegian population aged 12 years and older from 2008 to 2022 linked with information on health service use and cause of death. We used Cox regression with age as time axis to estimate sex-adjusted hazard ratios of suicide following discharge for ages 12 to 64 years and 65 years and older. We also performed analyses after excluding hospitalizations with indications of concurrent mental disorders, self-harm, or suicide attempts. To assess individual risk, we performed an adapted case-crossover analysis among discharged patients who died from suicide. RESULTS: A total of 4 632,980 individuals aged 12 to 64 years and 1,469,265 individuals aged 65 years and older were included. Compared to unexposed individuals at similar ages, we found an increased risk of suicide in the first 4 weeks after discharge, with a hazard ratio (HR) of 7.0 (95% confidence interval (CI) 5.9 to 8.3) among those aged 12 to 64 years and 6.8 (95% CI 5.4 to 8.6) among those 65 years and older. In the younger age group, the risk was attenuated, with a HR of 2.4 (95% CI 1.7 to 3.2) after excluding hospitalizations with indications of concurrent mental disorders, self-harm, or suicide attempts. The corresponding HR was 4.8 (95% CI 3.5 to 6.4) among those 65 years and older, declining to 1.9, (1.2 to 3.1) in weeks 5 to 8 and 1.2 (0.7 to 2.2) in weeks 21 to 24. The case-crossover analysis confirmed that individuals 65 years and older were particularly vulnerable. CONCLUSIONS: The heightened risk of suicide following discharge from acute somatic hospitalization, even in the absence of concurrent mental disorders, self-harm, or prior suicide attempts, underscores the critical need for comprehensive mental health and existential support for patients post-discharge.

Risk of suicide in patients with atrial fibrillation receiving different oral anticoagulants: a nationwide analysis using target trial emulation framework.

BACKGROUND: The suicide risk in patients with atrial fibrillation receiving novel oral anticoagulants or warfarin has not been evaluated in real-world practice. Moreover, reducing vitamin K levels may increase the suicide risk, underscoring the importance of selecting appropriate oral anticoagulants to prevent unintended outcomes. Therefore, we aimed to evaluate the association between different types of oral anticoagulants and the risk of attempted and completed suicide among patients with atrial fibrillation. METHODS: This nationwide study retrieved data from Taiwan's National Health Insurance Research Database from 2012 to 2020. This study included patients with atrial fibrillation aged 20 years and older who newly received oral anticoagulant treatment, and who had no contraindications for NOACs and no history of suicide-related events. The main outcomes were suicide-related outcomes, including attempted suicide and completed suicide. This study employed the target trial emulation framework to improve the causal inference for the observed association.  RESULTS: A total of 103,768 (71.74%) patients taking NOACs and 40,877 (28.26%) patients taking warfarin were included in this study. Compared to those receiving warfarin, patients receiving NOACs were associated with a lower risk of suicide-related outcomes (HR, 0.82; 95% CIs, 0.69-0.96). CONCLUSIONS: The findings of this cohort study suggested that patients receiving NOACs were associated with a lower risk of suicidal attempts but similar risk of complete suicide, compared to those receiving warfarin. Considering the risk of suicide, NOACs could be the preferred anticoagulants for patients with atrial fibrillation.