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Abstract: Background & Objectives: Depression and suicidal ideation are prevalent in patients with opioid use disorder (OUD). This study examined changes in suicidal ideation during OUD treatment with buprenorphine-naloxone or extended-release naltrexone using data from CTN-0051. Methods: 570 adults with OUD (29.6% female) were recruited into a National Drug Abuse Clinical Trials Network randomized trial (CTN-0051) comparing extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT). Suicidal ideation was assessed at baseline and regular intervals over 24 weeks using continuous self-reported and binary clinician-rated measures from the Concise Health Risk Tracking-Self Report and the Hamilton Depression Rating Scale, respectively. A mixed-effects model was used to assess the association between continuous outcome self-reported suicidal ideation and treatment over time while adjusted for baseline suicidal ideation. Results: Continuous self-report suicidal ideation scores decreased in both groups with a significant time-by-treatment interaction indicating that the treatment effect differed over time (F(11, 3497) = 1.81, p = .0464). Scores were significantly lower in the buprenorphine group only in weeks 1 and 3 and when averaged across weeks 1-4. Binary clinician-rated suicidal ideation dropped from 15 (5.25%) and 12 (4.24%) at baseline, to 5 (1.89%) and 3 (1.49%) at week 1, for buprenorphine and naltrexone groups, respectively. Conclusions: OUD treatment with extended-release naltrexone or buprenorphine-naloxone was associated with suicidal ideation reductions from the first week. Suicidal ideation was lower with buprenorphine-naloxone in the first 4 weeks, with no significant differences thereafter. Despite overall low suicidal ideation scores and modest differences, these findings suggest beneficial effects of both treatments in individuals with OUD and mild baseline suicidality. Related protocols: CTN-0051

Abstract:

Introduction: Individuals with opioid use disorder are at elevated suicide risk, but systematic screening in this population is rarely done. This study assessed the effects of targeted clinical decision support prompts on structured suicide risk assessment completion.

Methods: The study used a cluster-randomized controlled pragmatic pilot design. Adult primary care patients (aged 18-75 years) with or at risk for opioid use disorder or opioid overdose and suicide were eligible. Patients sought care from 15 Midwestern primary care clinics between July, 31, 2021 and July, 31, 2022. Data were analyzed between March and June 2023. Clinicians in intervention and control clinics received a printout from rooming staff, prompted by a clinical decision support-generated electronic health record alert, suggesting clinicians talk with patients about opioid risks. Intervention clinician handouts also alerted them to patients estimated to be at increased suicide risk and recommended completion of a Columbia Suicide Severity Rating Scale to further evaluate suicide risk. The handouts for control clinicians did not include suicide risk alerts. The main outcome measured the completion of the Columbia Suicide Severity Rating Scale in the 14 days following a visit.

Results: A total of 115 eligible patients (69 intervention, 46 control) made at least 1 visit to a randomized clinic. Patients mean age was 39 years, and 57% were women; 48% of patients had a high risk of opioid use disorder or opioid overdose, 39% had an opioid use disorder diagnosis, 12% had an opioid use disorder in remission diagnosis, and 5% had a recent opioid overdose. Over a mean follow-up of 249 days, 20.3% of intervention patients and 17.4% of control patients had at least 1 Columbia Suicide Severity Rating Scale completed in the next 14 days (p=0.70). Most (71%-75%) Columbia Suicide Severity Rating Scale scores were 0, indicating no risk.

Conclusions: This pilot study did not increase the uptake of structured suicide risk assessments in primary care for patients at elevated risk for opioid use disorder and suicide. More robust interventions are likely needed to promote suicide risk assessment in primary care.

Related protocols: CTN-0095-A-1

Abstract:

In their complementary presentations, Drs. Hammond and Hinckley discuss the association between cannabis use and suicide-related outcomes among youth and young adults. Dr. Hammond presents findings from a study that used 20 years of national mortality data to examine the impact of medical and recreational cannabis legalization on suicide-related mortality among US 12-to-25-year-olds, focusing on variations by age, sex, race, and ethnicity. These findings are discussed within the context of current medical literature on cannabis policy effects and health disparities, with an emphasis on mechanisms, vulnerable
subgroups, and legislative reform. Dr. Hinckley presents data from a secondary analysis of the National Comorbidity Survey-Adolescent Supplement, involving youth aged 13-18. This study explores the association between cannabis use, major depressive disorder, and suicidal behavior. Findings are considered within existing literature to further understand how cannabis use and depression together may increase suicide risk among youth.

Abstract:

Suicide is the tenth leading cause of death in the United States and continues to be a major public health concern. Suicide risk is highly prevalent among individuals with co-occurring substance use disorders (SUD) and mental health disorders, making them more prone to adverse substance use related outcomes including overdose. Identifying individuals with SUD who are suicidal, and therefore potentially most at risk of overdose, is an important step to address the synergistic epidemics of suicides and overdose fatalities in the United States. The current study assesses whether patterns of suicidality endorsement can indicate risk for substance use and overdose.

Latent class analysis (LCA) was used to assess patterns of item level responses to the Concise Health Risk Tracking Self-Report (CHRT-SR), which measures thoughts and feelings associated with suicidal propensity. We used data from 2,541 participants with SUD who were enrolled across 8 randomized clinical trials in the National Drug Abuse Treatment Clinical Trials Network from 2012 to 2021 (CTN-0037, -0049, -0051, -0053, -0054, -0064, -0067, -0068). Characteristics of individuals in each class were assessed, and multivariable logistic regression was performed to examine class membership as a predictor of overdose. LCA was also used to analyze predictors of substance use days.

Three classes were identified and discussed: Class (1) Minimal Suicidality, with low probabilities of endorsing each CHRT-SR construct; Class (2) Moderate Suicidality, with high probabilities of endorsing pessimism, helplessness, and lack of social support, but minimal endorsement of despair or suicidal thoughts; and Class (3) High Suicidality with high probabilities of endorsing all constructs. Individuals in the High Suicidality class comprise the highest proportions of males, Black/African American individuals, and those with a psychiatric history and baseline depression, as compared with the other two classes. Regression analysis revealed that those in the High Suicidality class are more likely to overdose as compared to those in the Minimal Suicidality class (p = 0.04).

Conclusions: Suicidality is an essential factor to consider when building strategies to screen, identify, and address individuals at risk for overdose. The integration of detailed suicide assessment and suicide risk reduction is a potential solution to help prevent suicide and overdose among people with SUD.

Related protocols: CTN-0037, CTN-0049, CTN-0051, CTN-0053, CTN-0054, CTN-0064, CTN-0067, CTN-0068

Abstract:

The co-occurrence of suicidality and substance use disorders has been well established, but rating scales to examine suicidal behavior and risk are sparse among participants with substance use disorders. In this study, part of the CTN ADAPT-2 protocol (CTN-0068), researchers examined the psychometric properties of the 16-item Concise Health Risk Tracking Scale – Self Report (CHRT-SR16) to measure suicidality among adults with moderate-to-severe methamphetamine use disorder.

Participants (n = 403) with moderate-to-severe methamphetamine use disorder completed the CHRT-SR16 as part of a randomized, double-blind, placebo-controlled pharmacotherapy trial. The CHRT-SR16 factor structure was assessed using confirmatory factor analysis (CFA). Internal consistency was estimated with coefficients alpha (a) and omega ( ), test-retest reliability with intraclass correlation coefficient (ICC) and standard error of measurement, and convergent validity using Spearman’s rank order correlation coefficient test between CHRT-SR16 factors and the Patient Health Questionnaire (PHQ-9). The analyses utilized baseline and week 1 data (for test-retest reliability only).

CFA revealed a seven-factor model of Pessimism, Helplessness, Social Support, Despair, Impulsivity, Irritability, and Suicidal Thoughts as the best-fitting model. The CHRT-SR16 also exhibited strong internal consistency (a = 0.89; = 0.89), test-retest reliability (ICC = 0.78) and convergent validity with the PHQ-9 total score ( = 0.62).

Conclusions: The results of this study offer evidence for strong reliability and convergent validity of the CHRT-SR16, among the first validated instruments to measure Suicidal Thoughts and behavior in a population that is disproportionately experiencing overdose and death due to methamphetamine use. The CHRT-SR16 builds upon prior work with the CHRT-SR and allows for the novel assessment of impulsivity and irritability as possible risk factors for suicidal behavior.

Related protocols: CTN-0068

Abstract:

Increasing rates of overdose and overdose deaths are a significant public health problem. Research has examined co-occurring mental health conditions, including suicidality, as a risk factor for intentional and unintentional overdose among individuals with substance use disorder (SUD). However, this research has been limited to single site studies of self-reported outcomes.

The current research evaluated suicidality as a predictor of overdose events in 2541 participants who use substances enrolled across eight multi-site clinical trials completed within the National Drug Abuse Treatment Clinical Trials Network between 2012 to 2021 (CTN-0037, -0049, -0051, -0053, -0054, -0064, -0067, and -0068). The trials assessed baseline suicidality with the Concise Health Risk Tracking Self-Report (CHRT-SR). Overdose events were determined by reports of adverse events, cause of death, or hospitalization due to substance overdose, and verified through a rigorous adjudication process. Multivariate logistic regression was performed to assess continuous CHRT-SR score as a predictor of overdose, controlling for covariates.

CHRT-SR score was associated with overdose events (p=0.03) during the trial; the likelihood of overdose increased as continuous CHRT score increased (OR 1.02). Participants with lifetime heroin use were more likely to overdose (OR 3.08).

Conclusions: Response to the marked rise in overdose deaths should integrate suicide risk reduction as part of prevention strategies.

Related protocols: CTN-0037, CTN-0049, CTN-0051, CTN-0053, CTN-0054, CTN-0064, CTN-0067, CTN-0068

Abstract:

The co-occurrence of substance use disorders (SUD) and trauma-exposure is a risk factor for suicidal thoughts and behaviors (STB). However, traditional methods of measurement for suicidal thoughts and behaviors are limited by an overreliance on dichotomous (i.e., yes or no) and averaged/summed scale score measurements. Further, among trauma-exposed individuals with SUD, it remains unclear which specific demographic factors, types of SUDs, and trauma sequelae (e.g., posttraumatic stress disorder [PTSD] symptom clusters) may be associated with elevated STB.

The present study utilized item response theory to (a) generate empirically derived STB severity scores and, (b) examine which demographic factors, SUD diagnoses, and DSM-IV PTSD symptom clusters are associated with suicidality in a trauma-exposed sample with SUDs.

Female trauma-exposed participants with SUDs (N=544) were recruited from community substance use treatment facilities in the NIDA Clinical Trials Network (CTN). Clinician-administered interviews assessed STB, SUDs, and PTSD symptoms.

Results indicated that the unidimensional item response theory (IRT) model used to estimate latent STB severity scores fit well, with strong local reliability and higher levels of latent STB severity. Regression predictors of elevated STB severity included younger age, opioid dependence, and higher PTSD reexperiencing symptoms.

Conclusions: Despite the critical importance of understanding, assessing, and identifying STB in trauma-exposed populations with SUDs, research methodologies that measure these variables are limited. This study used an innovative statistical analytic methodology to examine STB in a way that mirrors the weighting of various factors in suicide risk assessment. The findings highlight that trauma-exposed women with substance dependence who are younger, have opioid dependence, and/or have higher reexperiencing symptoms may warrant focused suicide risk assessment and management strategies. Clinicians are advised to screen for and target opioid use disorders and reexperiencing symptoms when addressing suicidal thoughts and behavior in trauma-exposed individuals with SUDs. Future work to elucidate the mechanisms through which these relationships operate would be beneficial.

Abstract:

Stimulant use disorders are both common and associated with suicidal ideation and attempts. The psychometric properties of the 12-item Concise Health Risk Tracking Scale Self-Report (CHRT-SR), a measure that was created to assess suicidal thinking and several factors associated with a propensity to act, has been established in persons with mood disorders. This is a secondary analysis to assess the CHRT-SR in 302 stimulant abusing patients who had participated in a clinical trial (NIDA Clinical Trials Network protocol CTN-0037, Stimulant Reduction Intervention Using Dosed Exercise (STRIDE)).

A confirmatory factor analysis (CFA) was conducted to assess the factor validity of the 12-item CHRT-SR model with a second-order Propensity factor. The CHRT-SR total score and 2 factor scores (Propensity and Suicidal Thoughts) demonstrated acceptable internal consistency and test-retest reliabilities. These two subscales and the total score were modestly but significantly associated with measures of depression and life satisfaction, demonstrating construct validity. Two additional items assessing Impulsivity were also analyzed, and demonstrated acceptable internal consistency, test-retest reliability, and construct validity.

Conclusions: The CHRT-SR appears to be a reliable and valid tool to assess suicidality in persons with stimulant use disorder. The value of a brief self-report measure of suicidal risk with promising psychometric properties has strong implications for practice and for clinical trials. The CHRT-SR is straightforward, requiring minimal clinician time to train and administer, and offers particular utility as a simple and quick assessment of helplessness and pessimism, symptoms common among people with chronic stimulant use, a population who should be closely monitored for suicide.

Related protocols: CTN-0037

Abstract:

This study compared the cause-specific standardized mortality ratios (SMRs) and expected years of life lost (EYLL) among opioid-dependent individuals in the United States and Taiwan. Survival data came from two cohorts followed until 2014: The U.S. data were based on a randomized trial of 1267 opioid-dependent participants enrolled between 2006 and 2009, the CTN START study (CTN-0027); the Taiwan data were from a study of 983 individuals that began in 2006, when opioid agonist treatment (OAT) was implemented in Taiwan. SMRs were calculated for each national cohort and compared. Kaplan-Meier estimation was performed on the survival data, then lifespans were extrapolated to 70 years (840 months) to estimate life expectancy using a semi-parametric method. EYLLs for both cohorts were estimated by subtracting their life expectancies from the age- and gender-matched referents within the general population of their respective country.

Compared with age- and gender-matched references, the SMRs were 3.2 for the U.S. sample and 7.8 for the Taiwan sample; the EYLLs were 7.7 and 16.4 years, respectively. Half of decedents died of unnatural causes in both cohorts; overdose deaths predominated in the U.S. and suicide in Taiwan (with suicide mortality among the Taiwan OAT group 20 times greater than that of the U.S. START group).

Conclusions: Despite different contexts in two vastly different countries, the current estimates of EYLL highlight that opioid dependence and its associated comorbidities and risk factors still contribute severe health burdens across regions. This comparison of cause-specific SMRs could inform stakeholders as they make health policy modifications relevant to their region. Given the prominent role of overdose in the U.S. START cohort, improving access to medication-assisted treatment to prevent overdoses or naloxone to treat them will help address the problem. Suicide is preventable; intervention strategies, including regular screening of ideation and depressive symptoms and providing treatment and support among opioid users in OAT treatment, are urgently needed in Taiwan.

Related protocols: CTN-0027

Abstract:

This study aimed to determine if current comorbid psychiatric disorders differ in adults with cocaine use disorder, other stimulant (primarily methamphetamine) use disorder, or both, and identify demographic and clinical characteristics in those with increasing numbers of comorbid disorders. Baseline data from participants enrolled in the NIDA Clinical Trials Network’s “Stimulant Reduction Intervention using Dosed Exercise” (STRIDE) study, a multisite randomized controlled trial that compared the efficacy of high intensity exercise and health education, both augmented to substance abuse treatment as usual in adults with stimulant use disorders entering residential treatment settings (N=302). Mood disorders were present in 33.6%, and anxiety disorders in 29.6%, with no differences among stimulant use disorder groups. Panic disorder was more frequently present with other stimulant use disorder. Those with two or more comorbid psychiatric disorders were more often female, white, had more symptoms of depression, greater propensity and risk for suicidal behavior, lower functioning in psychiatric and family domains, lower quality of life, more symptoms with stimulant abstinence and greater likelihood of marijuana dependence. Those with one or more comorbid disorders had more medical disorder burden, lower cognitive and physical functioning, greater pain, and higher rates of other drug dependence.

With current comorbid psychiatric disorders, the morbidity of stimulant use disorders increases. Use of validated assessments near treatment entry, and a treatment plan targeting not only substance use and comorbid psychiatric disorders, but functional impairments, medical disorder burden and pain, may be useful.

Related protocols: CTN-0037

Abstract:

Already the most commonly used illicit drug worldwide, cannabis continues to rise in popularity as the perception of its harmfulness decreases and evidence of its deleterious developmental effect increases. While internalizing distress and suicide risk have been linked with cannabis use problems (DSM-5 cannabis use disorder (CUD); DSM-IV cannabis abuse and dependence) it remains unclear how this association varies over the course of development in treatment-seeking men and women.

The current study utilized the NIDA Clinical Trials Network (CTN) to conduct a cross-sectional comparison of internalizing distress and suicide risk among men (n=437) and women (n=163) spanning ages 18-50 who met DSM-5 criteria for CUD (the sample was comprised of participants who had been screened for participation in CTN-0053). Interactions between gender and developmental stage (i.e., late adolescent, early adulthood, and middle adulthood) were observed for suicide risk and anxiety but not depression problems. Specifically, women seeking CUD treatment in late adolescence and middle adulthood exhibited significantly higher rates of anxiety and suicide risk compared to men seeking treatment during the same developmental stage. Internalizing distress and suicide risk did not differ between treatment-seeking men and women in the early adult stage.

Conclusions: This study is the first to utilize a gender differences framework to estimate how concurrent psychosocial problems associated with CUD may be moderated by development stage in those presenting for care. Results suggest that the structure of risk for CUD may differ in men and women across the lifespan and that women presenting for CUD treatment during late adolescence and middle adulthood may uniquely benefit from intervention designed to address these elevations in anxiety and suicide risk.

Related protocols: CTN-0053

Abstract:

Persons addicted to alcohol and drugs are at 5-10 times higher risk for suicide as compared to the general population. To address the need for improved suicide prevention strategies in this population, the Preventing Addiction Related Suicide (PARS) module was developed. Pilot testing of 78 patients from agencies participating the Pacific Northwest Node of the National Drug Abuse Treatment Clinical Trials Network (CTN), all of which offered standard, group-based intensive outpatient program addiction treatment, demonstrated significant post-treatment changes in knowledge and attitudes toward suicide prevention issues. Significant gains were maintained at 1-month follow-up for changes in knowledge, with changes in positive help seeking behaviors in dealing with suicidal issues in friends, family, and self also observed. The PARS was also highly rated by treatment staff as feasible within their standard clinical practice.

Conclusions: In conclusion, the pilot study of the PARS strongly suggests that broad based suicide prevention in intensive outpatient addiction treatment groups is not only possible but feasible, acceptable, and possibly effective. The pilot data presented here are promising and suggest that futher development and testing of the PARS program or other suicide prevention strategies in addiction treatment settings are indicated.