Significant shared heritability underlies suicide attempt and clinically predicted probability of attempting suicide.

Suicide accounts for nearly 800,000 deaths per year worldwide with rates of both deaths and attempts rising. Family studies have estimated substantial heritability of suicidal behavior; however, collecting the sample sizes necessary for successful genetic studies has remained a challenge. We utilized two different approaches in independent datasets to characterize the contribution of common genetic variation to suicide attempt. The first is a patient reported suicide attempt phenotype asked as part of an online mental health survey taken by a subset of participants (n = 157,366) in the UK Biobank. After quality control, we leveraged a genotyped set of unrelated, white British ancestry participants including 2433 cases and 334,766 controls that included those that did not participate in the survey or were not explicitly asked about attempting suicide. The second leveraged electronic health record (EHR) data from the Vanderbilt University Medical Center (VUMC, 2.8 million patients, 3250 cases) and machine learning to derive probabilities of attempting suicide in 24,546 genotyped patients. We identified significant and comparable heritability estimates of suicide attempt from both the patient reported phenotype in the UK Biobank (h2SNP = 0.035, p = 7.12 × 10-4) and the clinically predicted phenotype from VUMC (h2SNP = 0.046, p = 1.51 × 10-2). A significant genetic overlap was demonstrated between the two measures of suicide attempt in these independent samples through polygenic risk score analysis (t = 4.02, p = 5.75 × 10-5) and genetic correlation (rg = 1.073, SE = 0.36, p = 0.003). Finally, we show significant but incomplete genetic correlation of suicide attempt with insomnia (rg = 0.34-0.81) as well as several psychiatric disorders (rg = 0.26-0.79). This work demonstrates the contribution of common genetic variation to suicide attempt. It points to a genetic underpinning to clinically predicted risk of attempting suicide that is similar to the genetic profile from a patient reported outcome. Lastly, it presents an approach for using EHR data and clinical prediction to generate quantitative measures from binary phenotypes that can improve power for genetic studies.

Machine learning in suicide science: Applications and ethics.

For decades, our ability to predict suicide has remained at near-chance levels. Machine learning has recently emerged as a promising tool for advancing suicide science, particularly in the domain of suicide prediction. The present review provides an introduction to machine learning and its potential application to open questions in suicide research. Although only a few studies have implemented machine learning for suicide prediction, results to date indicate considerable improvement in accuracy and positive predictive value. Potential barriers to algorithm integration into clinical practice are discussed, as well as attendant ethical issues. Overall, machine learning approaches hold promise for accurate, scalable, and effective suicide risk detection; however, many critical questions and issues remain unexplored.

Depression and hopelessness as risk factors for suicide ideation, attempts and death: meta-analysis of longitudinal studies.

BACKGROUND: Many studies have documented robust relationships between depression and hopelessness and subsequent suicidal thoughts and behaviours; however, much weaker and non-significant effects have also been reported. These inconsistencies raise questions about whether and to what degree these factors confer risk for suicidal thoughts and behaviours.AimsThis study aimed to evaluate the magnitude and clinical utility of depression and hopelessness as risk factors for suicide ideation, attempts and death. METHOD: We conducted a meta-analysis of published studies from 1971 to 31 December 2014 that included at least one longitudinal analysis predicting suicide ideation, attempt or death using any depression or hopelessness variable. RESULTS: Overall prediction was weaker than anticipated, with weighted mean odds ratios of 1.96 (1.81-2.13) for ideation, 1.63 (1.55-1.72) for attempt and 1.33 (1.18-1.49) for death. Adjusting for publication bias further reduced estimates. Effects generally persisted regardless of sample severity, sample age or follow-up length. CONCLUSIONS: Several methodological constraints were prominent across studies; addressing these issues would likely be fruitful moving forward.Declaration of interestNone.

Predicting suicide attempts in adolescents with longitudinal clinical data and machine learning.

BACKGROUND: Adolescents have high rates of nonfatal suicide attempts, but clinically practical risk prediction remains a challenge. Screening can be time consuming to implement at scale, if it is done at all. Computational algorithms may predict suicide risk using only routinely collected clinical data. We used a machine learning approach validated on longitudinal clinical data in adults to address this challenge in adolescents. METHODS: This is a retrospective, longitudinal cohort study. Data were collected from the Vanderbilt Synthetic Derivative from January 1998 to December 2015 and included 974 adolescents with nonfatal suicide attempts and multiple control comparisons: 496 adolescents with other self-injury (OSI), 7,059 adolescents with depressive symptoms, and 25,081 adolescent general hospital controls. Candidate predictors included diagnostic, demographic, medication, and socioeconomic factors. Outcome was determined by multiexpert review of electronic health records. Random forests were validated with optimism adjustment at multiple time points (from 1 week to 2 years). Recalibration was done via isotonic regression. Evaluation metrics included discrimination (AUC, sensitivity/specificity, precision/recall) and calibration (calibration plots, slope/intercept, Brier score). RESULTS: Computational models performed well and did not require face-to-face screening. Performance improved as suicide attempts became more imminent. Discrimination was good in comparison with OSI controls (AUC = 0.83 [0.82-0.84] at 720 days; AUC = 0.85 [0.84-0.87] at 7 days) and depressed controls (AUC = 0.87 [95% CI 0.85-0.90] at 720 days; 0.90 [0.85-0.94] at 7 days) and best in comparison with general hospital controls (AUC 0.94 [0.92-0.96] at 720 days; 0.97 [0.95-0.98] at 7 days). Random forests significantly outperformed logistic regression in every comparison. Recalibration improved performance as much as ninefold - clinical recommendations with poorly calibrated predictions can lead to decision errors. CONCLUSIONS: Machine learning on longitudinal clinical data may provide a scalable approach to broaden screening for risk of nonfatal suicide attempts in adolescents.

Implicit attitudes toward eating stimuli differentiate eating disorder and non-eating disorder groups and predict eating disorder behaviors.

OBJECTIVE: The current study tested whether people with and without eating disorders (EDs) varied in their implicit attitudes toward ED-relevant stimuli. Additionally, the study tested whether implicit evaluations of ED-relevant stimuli predicted ED symptoms and behaviors over a 4-week interval. METHOD: Participants were people without EDs (N = 85) and people seeking treatment for EDs (N = 92). All participants completed self-report questionnaires and a version of the affect misattribution procedure (AMP) at baseline. The AMP indexed implicit evaluations of average body stimuli, eating stimuli, and ED-symptom stimuli. Participants with EDs completed weekly follow-up measures of ED symptoms and behaviors for 4 weeks. RESULTS: Contrary to predictions, the anorexia nervosa (AN) group did not differ from the no ED group on implicit attitudes toward ED-symptom stimuli, and the bulimia nervosa (BN) group had less positive implicit attitudes toward ED-symptom stimuli relative to the no ED group. In line with predictions, people with AN and BN had more negative implicit attitudes toward average body and eating stimuli relative to the no ED group. In addition, among the ED group more negative implicit attitudes toward eating stimuli predicted ED symptoms and behaviors 4 weeks later, over and above baseline ED symptoms and behaviors. DISCUSSION: Taken together, implicit evaluations of eating stimuli differentiated people with AN and BN from people without EDs and longitudinally predicted ED symptoms and behaviors. Interventions that increase implicit liking of eating-related stimuli may reduce ED behaviors.

Is externalizing psychopathology a robust risk factor for suicidal thoughts and behaviors? A meta-analysis of longitudinal studies.

OBJECTIVE: Our primary objective was to determine the potency of externalizing psychopathology as a risk factor for suicidal thoughts and behaviors (STBs). METHOD: We conducted a random effects meta-analysis of 174 prospective studies (839 unique statistical tests) examining externalizing psychopathology and suicidal thoughts and behaviors (STBs) published prior to December 8, 2017. The weighted mean odds ratios for the overall relationship between externalizing psychopathology and STBs were below 2.00 in magnitude, and all risk factor subcategories were also fairly modest predictors of STBs. Taking publication bias into account reduced the magnitude of these associations, particularly for death. Although externalizing psychopathology modestly predicts STBs, this may be due to design limitations of existing studies. Future research should employ shorter follow-up periods, consider risk factors in combination, and focus on forms of externalizing psychopathology that have not been studied extensively. RESULTS: The weighted mean odds ratios for the overall relationship between externalizing psychopathology and STBs were below 2.00 in magnitude, and all risk factor subcategories were also fairly modest predictors of STBs. Taking publication bias into account reduced the magnitude of these associations, particularly for death. Additionally, our results were mostly consistent regardless of sample age, sample severity, follow-up length, and predictor scale. CONCLUSIONS: Although externalizing psychopathology modestly predicts STBs, this may be due to design limitations of existing studies. Future research should employ shorter follow-up periods, consider risk factors in combination, and focus on forms of externalizing psychopathology that have not been studied extensively.

How to Implement Therapeutic Evaluative Conditioning in a Clinical Setting.

Self-injurious behaviors (SIBs), including both suicidal and nonsuicidal self-injury, are major public health problems that have been on the rise in recent decades. There are few effective SIB interventions, and those that are effective cannot reach most people who are in need of help-that is, these interventions are not scalable. To address this need, we recently developed a scalable, app-based treatment called Therapeutic Evaluative Conditioning (TEC) that preliminary studies have shown causes reductions in SIBs (Franklin et al., 2016). Although TEC was developed and evaluated as a standalone, self-administered intervention, it may also be a valuable therapeutic tool within traditional clinical settings. Here we provide a case illustration of a young adult female who presented at an outpatient clinic with a long history of self-injurious behaviors and multiple failed treatment attempts. In discussing this case, we describe how to implement TEC within such a setting and what might be expected as a result.

Does the timing of suicide risk assessments influence ratings of risk severity?

Clinicians are often tasked with identifying and managing patients who are at risk for suicide. Therefore, greater understanding of factors that impact the efficacy of suicide risk assessments (SRA) are of critical importance. One potential factor that may affect assessments of risk severity is the timing of the evaluation during clinical interview. Given that some patients are reluctant to disclose suicide-related symptoms, it is possible that asking about suicide at the beginning of an interview elicits more false negatives. It is also possible that if risk assessments are conducted in a manner that is encouraging to the patient, timing does not significantly impact patient report. This study examined whether SRA timing within an initial intake interview affects risk severity ratings. Adult psychiatric outpatients (N=169) were randomly assigned to receive a SRA during the beginning or middle of a one-hour intake. We failed to find a significant difference in suicide risk ratings between those who were evaluated at the beginning as compared to the middle of intake (14% versus 15% rated at elevated risk). Findings were not moderated by age, gender, or attempt history. Our results provide preliminary evidence that the timing of SRA may not impact risk severity ratings.

Does the interpersonal-Psychological theory of suicide provide a useful framework for understanding suicide risk among eating disorder patients? A test of the validity of the IPTS.

OBJECTIVE: The current study tested whether the Interpersonal-Psychological Theory of Suicide (IPTS) provides a useful framework for understanding elevated suicide rates among individuals with eating disorders (EDs). METHOD: Based on predictions of the IPTS, we tested whether the combination of thwarted belongingness and perceived burdensomeness was associated with suicidal desire, and whether the combination of thwarted belongingness, perceived burdensomeness, and fearlessness about death was associated with past suicide attempts in an ED sample (n = 100). We also compared these IPTS constructs in an ED sample versus general psychiatric inpatients (n = 85) and college students (i.e., non-clinical comparison group; n = 93). RESULTS: Within the ED sample, no hypothesized interactions were found, but perceived burdensomeness was associated with suicidal desire, and perceived burdensomeness and fearlessness about death were associated with past suicide attempts. The ED and psychiatric samples had greater thwarted belongingness, perceived burdensomeness, and suicidal desire than the non-clinical comparison group. DISCUSSION: The IPTS constructs of perceived burdensomeness and fearlessness about death appear to explain some facets of suicidality among people with EDs, but overall, support for the IPTS was limited. Future research on EDs and suicidality should look beyond the IPTS and consider other biological and sociocultural factors for suicide. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:1082-1086).

SURVEY OF TOXOPLASMA GONDII ANTIBODIES IN MAGELLANIC PENGUINS (SPHENISCUS MAGELLANICUS FORSTER, 1781).

Magellanic penguins (Spheniscus magellanicus) breed on the Atlantic and Pacific coasts of the southernmost parts of South America and migrate northward as far as Peru and Brazil. Serum samples (n = 100) from Magellanic penguins from three zoos and two rehabilitation centers (RCs) in Brazil were assayed for the presence of antibodies to Toxoplasma gondii by means of the modified agglutination test (MAT, cut-off ≥ 20). The penguins were categorized as young (≤4 yr old) or adults (≥4 yr old) and sexed (male, female, or not identified), and data were analyzed using the chi-square test (P ≤ 0.05). Toxoplasma gondii antibodies were found in 28% of penguins: 25.8% males, 27.8% females, 30.3% unknown sex, 25.4% young, and 31.1% adults. Statistical analyses did not find any difference (P > 0.05) with respect to age, sex, or source of birds. This is the first report of T. gondii antibodies in S. magellanicus.

An investigation of the interactive effects of the capability for suicide and acute agitation on suicidality in a military sample.

BACKGROUND: According to the interpersonal theory of suicide (1, 2), the difficulties inherently associated with death by suicide deter many individuals from engaging in suicidal behavior. Consistent with the notion that suicide is fearsome, acute states of heightened arousal are commonly observed in individuals immediately prior to lethal and near-lethal suicidal behavior. We suggest that among individuals who possess elevated levels of the capability for suicide, the heightened state of arousal experienced during periods of acute agitation may facilitate suicidal behavior in part because it would provide the necessary energy to approach a potentially lethal stimulus. Among individuals who are low on capability, the arousal experienced during agitation may result in further avoidance. METHODS: In the present project we examine how acute agitation may interact with the capability for suicide to predict suicidality in a large military sample (n = 1,208) using hierarchical multiple regression. RESULTS: Results were in line with a priori hypotheses: among individuals high on capability, as agitation increases, suicidality increases whereas as agitation increases among individuals low on capability, suicidality decreases. Results held beyond the effects of thwarted belongingness, perceived burdensomeness, and suicidal cognitions. CONCLUSIONS: Beyond further substantiating the link between agitation and suicide, findings of the present study provide evidence for the construct validity of the acquired capability as well as offer initial evidence for moderating role of capability on the effect of agitation on suicide. Limitations of the current study highlight a need for future research that improves upon the techniques used in the present study. Implications for science and practice are discussed.

Eating Disorder Symptoms and Suicidal Ideation: The Moderating Role of Disgust.

Disgust has been implicated as a factor that maintains and exacerbates eating disorder (ED) symptoms. Emerging research suggests that disgust may be a risk factor for suicidality. Given the high rates of suicidality among individuals with EDs, we propose that disgust may contribute to the link between EDs and suicidality. To test this hypothesis, self-report data were collected from 341 young adults (66% women). Cross-sectional associations between disgust with the self, others and the world and disgust sensitivity and propensity, ED symptoms and suicidal ideation were examined using multivariate regression analyses. ED symptoms and body dissatisfaction were associated with increased suicidal ideation at high levels of disgust with the self and the world; at low levels of disgust, ED symptoms and body dissatisfaction did not significantly relate to suicidal ideation. Disgust may indicate risk for suicidal ideation among individuals with eating psychopathology.

Beyond words: Semantic satiation and the mental accessibility of the concept of suicide.

Disrupting the accessibility of the mental representation of suicide may be a possible pathway to a strategy for suicide prevention. Our study aims to theoretically evaluate this perspective by examining the impact of temporarily disrupting the concept of suicide on perceptions of suicide. Using a within-subject design, we tested the effects of semantic satiation targeting the word "suicide" on the perceptual judgment of suicide-relevant pictures in 104 young adults. On each trial, participants repeated aloud one of the three words (i.e., "accident," "murder," or "suicide") either three times (priming) or 30 times (satiation) and indicated whether a subsequent picture matched with the word. Results indicated that satiation of the word "suicide" slowed the accurate categorization of pictures related to all three words, and satiation of "murder" and "accident" delayed participants' judgment of suicide-relevant pictures. Our findings support that semantic satiation can render the suicide concept temporarily less accessible, thereby providing preliminary support for the strategy of concept disruption in suicide prevention.

Accounting for diversity in the treatment of suicide and self-injury: A systematic review of the past 50 years of randomized controlled trials.

PURPOSE: Patients receiving treatment for self-injurious thoughts and behaviors (SITBs) have diverse backgrounds, yet it remains unclear exactly who is represented in the current SITB treatment literature. METHODS: We conducted a systematic review of the past 50 years of randomized controlled trials (RCTs) testing SITB treatments to evaluate sampling practices and reporting of sample characteristics, as well as inclusion of global populations across the included 525 papers. We also assessed changes over the past five decades in these three domains. RESULTS: SITB RCTs frequently reported age and sex (98.6%-95.1%), less frequently reported race (83.4%-38.6%), socioeconomic status (48.1%-46.1%) and ethnicity (41.9%-8.1%), and rarely reported LGBTQ+ status (3.7%-1.6%). U.S.-based RCTs featured predominantly White, non-Hispanic, and non-LGBTQ+ samples. Most RCTs were conducted in high-income North American or European countries. Sample reporting practices, sample representativeness, and inclusion of global populations modestly and inconsistently improved over time. CONCLUSIONS: There has not been substantial improvement in reporting practices, sample representativeness, or inclusion of global populations in SITB RCTs over the past 50 years. Acknowledging who is being studied and representing diverse populations in SITB treatment research is key to connecting research advances with those who may need it most.

Is physical pain causally related to suicidal behavior: An experimental test.

Existing evidence suggests a link between physical pain and suicide, but the nature of this relationship remains unknown. To address this critical gap in knowledge, the present study leveraged a validated virtual reality (VR) suicide paradigm to experimentally examine the causal effects of physical pain on subsequent virtual suicidal behaviors. Based on previous findings, we hypothesized that physical pain would causally drive virtual suicidal behavior only if suicide was conceptualized as having desirable anticipated consequences (e.g., a means of escaping from current pain; an opportunity to avoid future pain). We tested this by randomizing 326 participants across four different conditions: a physical pain condition, an anticipated escape condition, an anticipated avoidance condition, and a control condition. As predicted, physical pain alone did not result in statistically significant increases in VR suicide rates; however, the anticipation that virtual suicidal behavior would result in the avoidance of future physical pain had a large causal effect on VR suicide rates (B = 1.61, p < .001, IRR = 5.01). We failed to find evidence that anticipating that VR suicide would provide an escape from currently experienced physical pain increases the likelihood of VR suicide. Our findings add to a growing body of evidence suggesting that the anticipated consequences of suicide (e.g., avoidance of future physical pain) may serve as primary causes of suicidal behavior.

External Validation and Updating of a Statistical Civilian-Based Suicide Risk Model in US Naval Primary Care.

Importance: Suicide remains an ongoing concern in the US military. Statistical models have not been broadly disseminated for US Navy service members. Objective: To externally validate and update a statistical suicide risk model initially developed in a civilian setting with an emphasis on primary care. Design, Setting, and Participants: This retrospective cohort study used data collected from 2007 through 2017 among active-duty US Navy service members. The external civilian model was applied to every visit at Naval Medical Center Portsmouth (NMCP), its NMCP Naval Branch Health Clinics (NBHCs), and TRICARE Prime Clinics (TPCs) that fall within the NMCP area. The model was retrained and recalibrated using visits to NBHCs and TPCs and updated using Department of Defense (DoD)-specific billing codes and demographic characteristics, including expanded race and ethnicity categories. Domain and temporal analyses were performed with bootstrap validation. Data analysis was performed from September 2020 to December 2022. Exposure: Visit to US NMCP. Main Outcomes and Measures: Recorded suicidal behavior on the day of or within 30 days of a visit. Performance was assessed using area under the receiver operating curve (AUROC), area under the precision recall curve (AUPRC), Brier score, and Spiegelhalter z-test statistic. Results: Of the 260 583 service members, 6529 (2.5%) had a recorded suicidal behavior, 206 412 (79.2%) were male; 104 835 (40.2%) were aged 20 to 24 years; and 9458 (3.6%) were Asian, 56 715 (21.8%) were Black or African American, and 158 277 (60.7%) were White. Applying the civilian-trained model resulted in an AUROC of 0.77 (95% CI, 0.74-0.79) and an AUPRC of 0.004 (95% CI, 0.003-0.005) at NBHCs with poor calibration (Spiegelhalter P < .001). Retraining the algorithm improved AUROC to 0.92 (95% CI, 0.91-0.93) and AUPRC to 0.66 (95% CI, 0.63-0.68). Number needed to screen in the top risk tiers was 366 for the external model and 200 for the retrained model; the lower number indicates better performance. Domain validation showed AUROC of 0.90 (95% CI, 0.90-0.91) and AUPRC of 0.01 (95% CI, 0.01-0.01), and temporal validation showed AUROC of 0.75 (95% CI, 0.72-0.78) and AUPRC of 0.003 (95% CI, 0.003-0.005). Conclusions and Relevance: In this cohort study of active-duty Navy service members, a civilian suicide attempt risk model was externally validated. Retraining and updating with DoD-specific variables improved performance. Domain and temporal validation results were similar to external validation, suggesting that implementing an external model in US Navy primary care clinics may bypass the need for costly internal development and expedite the automation of suicide prevention in these clinics.

An examination of environmental and genetic contributions to the determinants of suicidal behavior among male twins.

The purpose of the present study was to examine the relative association of genetic and environmental factors with individual differences in each of the proximal, jointly necessary, and sufficient causes for suicidal behavior, according to the Interpersonal-Psychological Theory of Suicide (IPTS; Joiner, 2005). We examined data on derived scales measuring acquired capability, belongingness, and burdensomeness (the determinants of suicidal behavior, according to theory) from 348 adolescent male twins. Univariate biometrical models were used to estimate the magnitude of additive genetic (A), non-additive genetic (D), shared environmental (C), and non-shared environmental (E) effects associated with the variance in acquired capability, belongingness, and burdensomeness. The best fitting model for the acquired capability allowed for additive genetic and environmental effects, whereas the best fitting model for burdensomeness and belongingness allowed for shared and non-shared environmental effects. The present research extends prior work by specifying the environmental and genetic contributions to the components of the IPTS, and our findings suggest that belongingness and burdensomeness may be more appropriate targets for clinical intervention than acquired capability as these factors may be more malleable or amenable to change.

Does Body Mass Index Confer Risk for Future Suicidal Thoughts and Behaviors? A Meta-analysis of Longitudinal Studies.

PURPOSE OF REVIEW: Body mass index (BMI) outside of the "normal" range is commonly cited as a predictor of adverse health outcomes and has been identified as a potential risk factor for suicidal thoughts and behaviors (STBs). This meta-analysis provides a descriptive and quantitative summary of the literature evaluating the longitudinal relationship between BMI/weight status and STBs. RECENT FINDINGS: The longitudinal literature examining the relationship between BMI/weight status and STBs is small and methodologically constrained. Within the existing literature, BMI and weight status are generally weak or nonsignificant risk factors for STBs. It is possible that body weight has a complex relationship with physical and mental health, including STBs, which may not be possible to accurately capture with a singular metric such as BMI. BMI and weight status do not appear to robustly predict STBs, at least within the methodological constraints of the existing literature.

Suicide plan prevalence, recurrence, and longitudinal association with nonfatal suicide attempt.

BACKGROUND: Each year, millions of people develop suicide plans. These plans are assumed to indicate imminent suicide risk, yet this has rarely been tested. The present study seeks to address two questions: (1) how prevalent are specific thoughts of suicide plans among individuals with a history of suicidal thoughts and behaviors and (2) do suicide plans confer risk of future suicide attempts in the short term? METHODS: Secondary data analysis was performed on a longitudinal dataset (N = 1021). Prevalence and frequencies of suicide planning features (i.e., method, time, place) at baseline and 3, 14, and 28 days post-baseline were calculated. Logistic regressions were conducted to assess whether suicide plans confer risk of suicide attempts across a 28-day follow-up period. RESULTS: Suicide planning more commonly involved thoughts of method than place and/or time. High variability in suicide planning was evident and thoughts of suicide plans frequently recurred. Contrary to assumptions, suicide plans displayed weak associations with nonfatal suicide attempt across the 28-day follow-up period. CONCLUSIONS: Suicide plans appear heterogeneous in nature. They do not appear to play a strong role in predicting nonfatal suicide attempts. Re-evaluation of the central role that suicide plans occupy within clinical risk assessments may be warranted.

Efficacy of psychotropic medications on suicide and self-injury: a meta-analysis of randomized controlled trials.

Using psychotropic medications to treat and prevent self-injurious thoughts and behaviors (SITBs) has become increasingly popular, but conclusive evidence supporting the efficacy this approach remains elusive. To empirically examine whether psychotropic medications are efficacious treatments for SITBs, the present meta-analysis comprehensively summarizes all published randomized controlled trials (RCTs) that have reported the causal effects of psychotropic medications on suicide and self-injury. A total of 251 papers from 718 unique RCTs were included. A frequentist pairwise approach was adopted for meta-analyses. Potential effect modifiers were examined via met regressions and potential biases were evaluated through sensitivity analyses. On average, medications yielded an 8% reduction in SITB frequency and a reduction of 0.2 standard deviations in symptoms and severity. Findings were largely consistent across potential effect modifiers, and significant evidence of publication bias was not detected. Only one medication class (i.e., antipsychotics) and two specific medications (i.e., citalopram, ketamine) produced larger-than-average treatment effects. Psychostimulants and typical antipsychotics may produce iatrogenic effects. Less than 4% of included studies required individuals to exhibit SITBs, and nearly half of analyzed effects were drawn from studies that excluded individuals on the basis of SITB risk. Taken together, findings suggest that psychotropic medications produce small treatment effects on SITBs; however, these findings should be considered in light of the methodological constraints of the existing literature, including the lack of studies intentionally including individuals with SITBs. It is critical for future RCTs to prioritize including individuals with existing SITBs to further clarify treatment effects in self-injurious and suicidal populations. Additional research is needed to better understand the treatment mechanisms of psychotropic medications and identify the causal processes underlying SITBs.