Overdoses in the United States are increasingly driven by co-occurring stimulant and fentanyl use, yet limited research has examined individual-level stimulant use patterns over time. We assessed self-reported stimulant use among 505 people who use drugs enrolled in the Rhode Island Prescription and Illicit Drug Study (RAPIDS) from 2020 to 2024. Group-based trajectory modeling identified distinct patterns of past-month stimulant use over 12 months of follow-up. We examined associations between trajectories and sociodemographic characteristics, other substance use patterns, and mental health diagnoses. Four distinct stimulant use trajectories emerged: low (12%), low/moderate (52%), moderate/high (19%), and high (17%) use. The high-use group exhibited the highest proportion of people who were unhoused (82%, p < 0.01) and had injected drugs in the past month (42%, p < 0.01) at baseline. The high-use group also reported the highest proportions of a lifetime diagnosis of bipolar disorder (46%, p = 0.05), anxiety disorder (57%, p < 0.01), and psychosis (25%, p < 0.01) at baseline. Trajectory-based analyses by specific stimulant type revealed that powder cocaine decreased at three months compared to baseline, while other stimulant use (i.e., crack cocaine, crystal methamphetamine, extra-medical prescription stimulants) remained relatively stable over follow-up. Findings underscore the need for prevention and harm reduction-focused interventions in settings that serve people who are unhoused (e.g., living in homeless shelters, transitional programs) and those with diagnosed psychosis (e.g., receiving behavioral and mental health services).

Background: Between 3-5% of adolescents develop new persistent opioid use after surgery. Little is known about their recovery experience, including pain trajectory, pain treatment and prolonged opioid use. Methods: This prospective cohort study enrolled adolescents between June 2022 to May 2023 prior to undergoing select procedures associated with mild, moderate or severe postoperative pain (‘major procedures’). We collected data using text-message surveys at baseline, daily for the first two postoperative weeks and monthly for five months; baseline data are reported separately. The primary outcome was persistent pain at Month 3. Secondary outcomes included satisfaction with recovery, time in days to resolution of acute, severe pain, and prolonged opioid use (>2 weeks). We utilized generalized linear models (GLMs) to model resolution of surgical site pain over time. Results: The cohort included 340 adolescents with a median age of 15 years (IQR 13.5-17) who provided outcome data at Month 3, including 141 undergoing major procedures. Within this group, persistent surgical site pain was present at Month 3 among 57.9% (n=81), while only 9.2% (n=13) were ‘unhappy’ or ‘very unhappy’ with their recovery. Severe pain (NRS 7-10) resolved within 3 days (IQR 1-6) after surgery. However, prolonged opioid use in Weeks 3 and 4 was present among 39.6% (n=44). The odds of persistent surgical site pain declined by 25% (OR 0.75, 95% CI 0.67-0.83) each month, and female sex was the only significant individual predictor (OR 1.95, 95% CI 1.11-3.42 p=0.02). Trends were similar, but decreased in magnitude, among those recovering from mild and moderate pain procedures. Conclusions: After major surgery, a high proportion of adolescents endorsed persistent pain in Month 3 despite relative recovery satisfaction. In addition, an unanticipated number used opioids after resolution of severe pain for which opioids may be indicated.

Polysubstance use (PSU) initiation often occurs during adolescence and is associated with increased risk of psychiatric comorbidity and substance use disorders (SUDs), yet factors associated with PSU initiation remain poorly understood. Using the Adolescent Brain Cognitive Development Study (N=9,174; 6-year follow-up), we examined associations of PSU initiation with shared genetic liability, multidimensional environmental exposures, and functional brain connectivity. We found that polygenic risk for shared genetic vulnerability across multiple SUDs, derived from independent adult GWAS, was associated with increased likelihood of PSU initiation. Environmental risk factors for PSU included peer victimization and adverse life events, particularly among adolescents with high genetic susceptibility, whereas parental monitoring and family cohesion were protective. Adolescents who later initiated PSU showed altered subcortical-cortical functional connectivity across development. These findings suggest that adolescent PSU initiation may mark a broader pattern of developmental vulnerability associated with shared genetic liability, environmental adversity, and altered brain network development. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement PL was supported by grants from the U.S. National Institute of Health (R01MH119243, R01GM148494) and by Mass General Brigham Department of Psychiatry. JMG is supported by K02DA052684 and R01DA051540. JLR is supported by R01MH124694. The ABCD study is supported by the National Institutes of Health (NIH) and additional federal partners under award numbers U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123, U24DA041147. Additional support for this work was made possible from NIEHS R01-ES032295 and R01-ES031074. Funding supporting this study was provided by the Spanish Ministry of Science, Innovation, and Universities (PID2021-1277760B-I100 and PID2024-158634OB-I00, to BC and NFC), Government of Catalonia/AGAUR, (2021-SGR-01093, to BC and NFC), ICREA Academia 2021 (to BC), TV3 Marathon Foundation (202218-31, to BC) and Ministry of Health, Social Services, and Equality/National Plan on Drugs (PNSD-2020I042 and PNSD-2024|056, to NFC). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study utilizes publicly available data from the Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study is a nationwide clinical research initiative involving thousands of adolescents across 21 sites in the United States. Since the data used in this project are de-identified and publicly accessible, the research conducted using ABCD data qualifies for IRB exemption. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The Adolescent Brain Cognitive Development data used in this report are available from the NIMH Data Achieve (https://nda.nih.gov) to Authorized Users. We used open-source software packages from R, and publicly available methods, GenomicSEM, PLINK, PRS-CS.

Importance:The ongoing opioid-related overdose crisis in the US is increasingly affecting adolescents and is exacerbated by the widespread availability of illicitly manufactured fentanyl. Adolescents face significant gaps in care for prevention and treatment of opioid use and opioid-related harms. Regulatory changes have impacted the availability of 2 lifesaving medications, naloxone and buprenorphine. This narrative review summarizes the current knowledge of opioid use, overdoses, and opioid use disorder (OUD) among US adolescents in the context of fentanyl, and reviews the use of naloxone and buprenorphine, for overdose reversal and OUD treatment, respectively. Observations:Owing to their developmental stage, adolescents are uniquely vulnerable to initiating substances, experiencing substance-related harms, and developing substance use disorders. From 2018 through 2023, morbidity and mortality have increased from use of opioids, particularly fentanyl, among youth. Naloxone and buprenorphine are safe and highly effective medications for opioid overdose reversal and OUD treatment, respectively. Regulations for these medications have changed to address the worsening overdose epidemic. Naloxone is approved for over-the-counter sales (including by adolescents younger than 18 years). Any clinician with a US Drug Enforcement Administration-controlled substance license can now prescribe buprenorphine for OUD without a waiver. These policy changes present critical opportunities to save lives and reduce inequities among adolescents. Conclusion and Relevance:Harms from opioids are increasingly affecting adolescents with a notable rise in overdose fatalities in the past 5 years. Regulatory changes for naloxone and buprenorphine have occurred to improve access to both these medications. Despite these changes, adolescents continue to have low access to these life-saving interventions. Ensuring that clinicians have the knowledge to provide both medications to adolescents is a key step to addressing the epidemic of adolescent drug overdoses and reducing opioid-related harms.

Screening and brief intervention (SBI) is widely recommended to promote detection and early intervention for alcohol and other drug (AOD) use in pediatric primary care (PC). This multi-site randomized effectiveness trial screened 550 adolescent-caregiver dyads for AOD use risk factors in 3 urban PC practices. One hundred forty-eight adolescents at-risk for AOD use problems and their caregivers were enrolled in SBI-A-Standard, which included only adolescents in all intervention activities; or SBI-A-Family, which included both adolescents and caregivers in all SBI activities. Compared with SBI-A-Standard, SBI-A-Family procedures identified and provided intervention to more adolescents at risk for AOD use problems (47% of screened dyads vs 24%). Moreover, SBI-A-Family counseling interventions, although more extensive and resource demanding, were administered to 82% of indicated cases and rated near universally as helpful by adolescents, caregivers, and providers. Results of this study demonstrate added value of family-inclusive SBI models for identifying and addressing youth AOD use in PC.

BACKGROUND:Adolescents who fill an opioid prescription for surgery are at increased risk of adverse outcomes, including persistent opioid use, addiction, or overdose. Limited evidence suggests clinicians may increasingly prescribe gabapentin as an opioid-sparing strategy, although gabapentin is increasingly associated with adverse outcomes. The authors examined perioperative gabapentin and opioid prescribing trends over time. METHODS:Using a national private insurance claims database, the authors identified a cohort of gabapentin and opioid-naive adolescents 11 to 21 yr old who underwent seven procedures that are either common or associated with postoperative persistent opioid use between 2012 and 2022. The authors quantified initial gabapentin and opioid prescriptions, refills within 60 days, and number of days and pills dispensed and used multivariable logistic regression analysis to assess the association between gabapentin dispensing and opioid refills. RESULTS:Of 181,225 gabapentin and opioid-naive adolescents, 32.1% (n = 58,139) filled a new prescription for one or both. Specifically, 1.1% (n = 662) filled a gabapentin prescription, 96.7% (n = 56,210) filled an opioid prescription, and 2.2% (n = 1,267) filled both. Initial gabapentin prescriptions included a mean ± SD supply of 22.0 ± 15.0 days, 55.3% contained an initial daily dose 600 mg or greater, and 36.5% obtained one or more refills. Opioid-only prescriptions declined during the study period, while gabapentin prescriptions with and without opioid increased. Adolescents who filled both opioid and gabapentin versus opioid-only prescriptions had a 14% (95% CI, 11.0 to 16.8%) adjusted probability difference with regard to obtaining an opioid refill (40.7% vs. 21.6%). CONCLUSIONS:Gabapentin dispensing increased over time, and more than one third of adolescents were dispensed a refill prescription. Coprescription with opioids did not appear to be associated with decreased opioid quantity in the initial prescription or decreased likelihood of obtaining a refill opioid prescription after undergoing a study procedure. In addition, opioids were often prescribed when they were unlikely to be needed for postoperative pain management.

BACKGROUND:Adolescents are at increased risk of persistent postsurgical opioid use. Qualitative data may provide insight on protective experiences and guidance. STUDY DESIGN:Adolescents aged 11-21 years who were enrolled in a larger longitudinal survey study participated in semi-structured interviews one and three months after surgery between September 2022 and March 2023. Experiences were examined among adolescents who used opioids in postoperative weeks 3 and 4, after severe pain resolved. RESULTS:Fifty interviews with 46 adolescents undergoing common procedures associated with severe pain and/or persistent opioid use revealed that preoperative clinic conversations set an important framework for recovery. Positive experiences included normalizing anxiety, awareness of physical changes signifying recovery, including resolution of severe pain and subsequent opioid cessation, and effective non-opioid and non-pharmacologic pain treatment options, including ice and stretching. Patients with prolonged opioid use, whose caregivers often directed pain management, described more profound fears, struggles with seeking out information, difficulties actively engaging in recovery, and the use of opioids and sleep to avert pain. CONCLUSION:The preoperative visit and recovery framework provided by the surgical team played an important role in guiding the recovery experience. Factors that may offer protection against prolonged opioid use include realistic descriptions of the recovery process with common milestones, encouraging preparation and engagement in the work of recovery, and educating on the role of opioid, non-opioid, and non-pharmacologic pain management options, including when to stop using opioids.

BackgroundSince 2013, fentanyl has dominated unregulated drug supplies in the northeast and has become a key driver of overdose deaths. In this analysis, we sought to identify the characteristics associated with fentanyl use frequency among people who use drugs in Rhode Island. MethodsWe examined baseline data from the Rhode Island Prescription and Illicit Drug Study, which enrolled participants from August 2020 to February 2023. We used an ordinal logistic regression to identify sociodemographic and drug use characteristics that were associated with prior month fentanyl use frequency, which was categorized as none, less than weekly, or at least weekly. ResultsAmong 471 participants, 210 (44%) reported no prior month use of fentanyl or drugs containing fentanyl, 121 (26%) reported less than weekly use, and 140 (30%) reported at least weekly use. Of those who reported at least weekly use, 74% reported intentional use. In bivariate analyses, the proportion of participants utilizing harm reduction practices (e.g., fentanyl test strip use, naloxone carriage) increased with fentanyl use frequency in a dose-response manner. In adjusted analyses, prior month injection drug use, fentanyl preference, regular use of crack cocaine, lifetime overdose history, and current enrollment in opioid agonist therapy were significantly associated (p< 0.05) with greater fentanyl use frequency. ConclusionsFentanyl exposure and intentional fentanyl use were common in the sample. Our findings suggest a need for increased investment in community-based harm reduction services and low-barrier, patient-centered treatment for polysubstance use, including those involving stimulant use disorders.

AbstractAlcohol use is a major contributor to morbidity and mortality, but most individuals with problematic alcohol use do not receive evidence-based care or accurate information about drinking. Recommendations on safe levels of alcohol consumption are rapidly evolving, with recent research finding health and social harms at levels well below traditional lower-risk drinking guidelines. Screening tools to identify alcohol use are widely available but infrequently used. Alcohol withdrawal management protocols have not kept pace with recent evidence highlighting the safety and benefits of benzodiazepine-sparing approaches. Similarly, despite clear evidence on the efficacy of psychosocial treatments and evidence-based pharmacotherapies (e.g., naltrexone) to treat alcohol use disorders, most individuals do not receive such treatment. Research also shows a lack of benefit and potential harm of routine use of antidepressants and other psychotropic medications commonly prescribed to individuals with alcohol use disorders. There is a critical opportunity for clinicians across specialties and healthcare systems to better identify and address alcohol use.

BACKGROUND:Structural barriers can pose challenges to retaining people who use drugs in longitudinal research. This study assessed baseline characteristics associated with retention in a year-long clinical trial addressing whether fentanyl test strip provision decreased rates of nonfatal overdose among people who use drugs. METHODS:From September 2020 to February 2023, 505 participants enrolled in the year-long RAPIDS clinical trial. Outcome visits were completed at 6 and 12 months following enrollment. Bivariable and multivariable analyses were conducted to assess baseline characteristics associated with the completion of none, one, or both study outcome assessments. We used multinomial logistic regression to identify statistically significant baseline predictors of retention in the RAPIDS trial. RESULTS:Among eligible participants, 41.6% (n = 210) only completed a baseline assessment, 23.4% (n = 118) completed one outcome visit, and 35.0% (n = 177) completed both. In the final multinomial logistic regression model, women were more likely to complete both outcome visits compared to men (adjusted odds ratio [AOR] = 1.69, 95% CI: 1.08-2.62), while participants with a history of drug selling were less likely to complete two visits (AOR = 0.62, 95% CI: 0.39-0.98). CONCLUSIONS:Study results challenge stigmatizing beliefs about the impact of sociodemographic and drug use-related characteristics on retention in longitudinal research. Retention strategies that target men and people who sell drugs are needed. Investigators can collect multiple pieces of contact information, have monthly check-ins with participants, and partner with community organizations to make research more accessible and acceptable to structurally vulnerable populations.

PURPOSE:Adverse childhood experience (ACE) exposure and poor mental health are closely intertwined. In 2020, the prevalence of both began precipitously increasing among adolescents. We explored associations of individual and cumulative ACE exposure with cost and COVID-19 pandemic-related unmet health needs to assess ACEs as risk markers for broader structural adversity. METHODS:We conducted a nationally representative analysis of 5,536 adolescents (weighted N = 20,294,070) aged 13-17 years using the 2019 and 2021 National Health Interview Survey. Outcomes included mental health symptoms, preventive care access, cost and COVID-19-related unmet needs, and health care use. We estimated associations with lifetime exposure to 4 ACEs using marginal effects from multivariable logistic regressions. RESULTS:Millions of adolescents were exposed to parental incarceration (7.8%, N = 1,407,670), neighborhood violence (6.9%, N = 1,567,483), a guardian with serious mental illness (10.3%, N = 2,088,957), and/or a guardian with alcohol or drug problems (11.4%, N = 2,304,953). Overall, 77.7% (N = 15,758,023), 13.2% (N = 2,671,342), and 9.2% (N = 1,864,704) were exposed to 0, 1, and 2+ of these ACEs. In adjusted models, compared with exposure to 0 ACEs, exposure to 1 or 2+ ACEs was positively associated with anxiety and depression symptom frequency, urgent care and emergency department use, trouble paying medical bills, delayed and forgone mental health care due to cost, and delayed and forgone care due to the COVID-19 pandemic. DISCUSSION:Adolescents exposed to ACEs experienced mutually reinforcing disadvantages: a worse mental health symptom burden, yet greater barriers to accessing needed medical and mental health care. ACEs must be reconceptualized as markers of structural-rather than individual-adversity and addressed through structural and policy interventions.

BackgroundYouth and families play an indispensable role in health research, given their unique lived experiences and expertise. Aligning research with patients’ needs, values, and preferences can significantly enhance its relevance and impact; however, recent research has highlighted various challenges and risks associated with youth and family engagement in health research. These challenges encompass the perils of tokenism, power imbalances and dynamics, questioning the motives behind engagement, and limited accessibility to patient-friendly training for patient partners, as well as inadequate training on patient engagement for researchers and the absence of equitable engagement tools. To address these risks and challenges, different patient engagement models, theories, frameworks, and guiding principles have been developed and adopted; to date, however, their transferability to youth- and family-specific engagement in research has been limited. ObjectiveThe objectives of this project are (1) to determine the extent of the literature on the application of patient engagement models, theories, frameworks, and guiding principles in the context of youth-specific research; and (2) to determine how meaningful the key components and constructs of these models, theories, frameworks, and guiding principles are to youth and their family members. MethodsThis project will use an integrated knowledge translation approach and consists of 2 phases: (1) a scoping review to identify patient engagement models, theories, frameworks and guiding principles in youth research; and (2) a qualitative descriptive study using one-on-one semistructured interviews with youth and family members to understand their conceptualization of meaningful engagement in health research. For phase 1, the following databases were searched: Medline, CINAHL, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials. Literature from 2013 to August 28, 2024, was captured. Primary studies using a patient engagement in research model, theory, or framework, or guiding principles, in youth will be included. The risk of bias of included studies will not be assessed. Extracted data will be quantitatively summarized using numerical counts and qualitatively using content analysis. For phase 2, we will recruit 9 to 17 youth and 9 to 17 family members. Transcripts will be analyzed using an inductive approach outlined by Braun and Clarke. ResultsThe project has received funding from the Canadian Institutes of Health Research. A 9-member integrated knowledge translation panel consisting of 6 youth and 3 family members has been established. ConclusionsThe findings from this study will identify what is currently known about the application of patient engagement models, theories, frameworks, and guiding principles in youth-specific research and the important components of these models, theories, frameworks, and guiding principles from the perspective of youth and their families. These findings will be instrumental to developing a youth- and family-specific engagement in research framework called the UNITE framework and subsequently, a validated measure. International Registered Report Identifier (IRRID)PRR1-10.2196/65733

Background: As in much of the United States, there have been significant increases in overdose deaths among non-Hispanic Black and Hispanic/Latinx populations in Rhode Island over the past decade. Given the shifting dynamics of the overdose epidemic, there is an urgent need for focused interventions that address the specific needs of diverse communities. This study explores differences in drug use patterns, harm reduction behaviors and types and barriers to treatment by race and ethnicity. Methods: This study utilized baseline data from the Rhode Island Prescription and Illicit Drug Study (RAPIDS). We assessed sociodemographic characteristics, drug use patterns, harm reduction practices, treatment type, and barriers to treatment in a cross-sectional analysis of people who use drugs (PWUD), stratified by race and ethnicity (non-Hispanic white, non-Hispanic Black, non-Hispanic other race, and Hispanic). Chi-square tests of independence and ANOVA tests were used to identify statistically significant differences by race and ethnicity. Results: Among 509 participants, the median age was 43, and the majority were men (64%). Non-Hispanic Black participants reported significantly less regular use of unregulated opioids, such as heroin (10%) and fentanyl (12%), as compared to non-Hispanic white participants (39% and 33%, respectively). Non-Hispanic Black participants reported significantly less experience responding to overdoses: only 39% had ever administered naloxone and 34% had ever performed rescue breathing, as compared to 67% and 57% among non-Hispanic white participants, respectively. Despite significant differences in drug use patterns, there were few differences in harm reduction practices by race and ethnicity. Current treatment enrollment was highest among those who were non-Hispanic white (38%) and lowest among those who were non-Hispanic Black (7%). Conclusions: These findings suggest that there are differences in overdose response experience and treatment exposure between non-Hispanic Black PWUD and those belonging to other racial and ethnic groups, indicating a need for enhanced investment in overdose response education, naloxone distribution and treatment access for non-Hispanic Black PWUD.

This study examines trends in school programming related to mental health and substance use and teacher professional development across US middle and high schools from 2008 to 2020.

Background People experiencing homelessness have been disproportionately affected by the overdose crisis in the United States. We assessed whether an association exists between homelessness and fentanyl test strip (FTS) use to avoid drug overdose among people who use drugs in Rhode Island. Methods We recruited 505 participants aged 18-65 from September 2020 to February 2023 as part of the Rhode Island Prescription Illicit Drug Study (RAPIDS). Baseline data assessed correlates of past-month FTS use through bivariate and multivariable analyses. We used generalized estimating equations (GEE) to estimate the longitudinal association between past-month homelessness and FTS use over 12 months. Results At baseline, 19.3 % of the sample reported having used FTS in the past month, which was more commonly reported by those who were experiencing homelessness (22.6 %) compared to those who were housed (14.4 %), p = 0.021. In bivariable GEE analysis, past month homelessness was not associated with past-month FTS use (OR=1.22, 95 %CI: 0.95--1.56, p = 0.117). In multivariable GEE analysis, homelessness was not associated with FTS use, but regular use of crystal methamphetamine was (aOR = 2.13, 95 %CI: 1.42-3.19; p < 0.001). The odds of FTS use among persons recruited in 2023 increased by 165 % (aOR=2.65, 95 %CI: 1.22-5.76; p < 0.001) compared to those recruited in 2020. Conclusions We found that housing status was not independently and longitudinally associated with FTS use; however, people who used crystal methamphetamine were more than twice as likely to have used FTS in the past month. Future research exploring how differential housing situations may affect uptake of harm reduction services is needed to prevent fentanyl overdose.

OBJECTIVES It is unclear how long youth with opioid use disorder (OUD) should continue taking buprenorphine, and what adherence they should achieve. We identified patterns of duration/adherence and assessed associations with subsequent overdose, emergency department (ED) use, and hospitalization. METHODS This retrospective cohort analysis used 2014–2022 data from the Massachusetts Public Health Data Warehouse. We identified youth aged 13 to 26 years initiating buprenorphine and used group-based trajectory modeling to categorize youth into duration/adherence trajectories over 12 months. Using multivariable Cox regression, we examined associations between trajectories and time to fatal/nonfatal opioid overdose, all-cause ED use, and all-cause hospitalization during the subsequent 12-month period. RESULTS Among 11 649 Massachusetts youth initiating buprenorphine, most were aged 21 years or older (89.0%), male (60.3%), white non-Hispanic (85.9%), and enrolled in Medicaid (55.4%). We identified 4 patterns of medication use: (1) high adherence for 12 months (23.7%); (2) low adherence for 12 months (27.5%); (3) discontinuation in 3 to 9 months (16.4%); and (4) discontinuation in less than 3 months (32.5%). Trajectories included 580 (5.0%) and 774 (6.6%) youth switching to methadone and naltrexone, respectively. Compared with high adherence for 12 months, overdose risk was higher with low adherence for 12 months (adjusted hazard ratio [aHR], 1.46; 95% CI, 1.24–1.73), discontinuation in 3 to 9 months (aHR, 1.82; 95% CI, 1.52–2.17), and discontinuation in less than 3 months (aHR, 1.76; 95% CI 1.50–2.06). Compared with high adherence, low adherence and discontinuation in less than 3 months had higher risk of ED use, and all other trajectories had higher risk of hospitalization. CONCLUSIONS Medication adherence may prevent overdose, ED use, and hospitalization. Strategies to increase treatment duration/adherence likely avert harm.