This Week in Addiction Medicine from ASAM

Opioid and Naloxone Prescribing Following Insertion of Prompts in the Electronic Health Record to Encourage Compliance With California State Opioid Law [OPEN ACCESS] JAMA Network Open  In 2018, California passed Assembly Bill (AB) 2760, mandating coprescription of naloxone and opioids for patients with high overdose risk. The current study assessed whether electronic prompts were associated with increased naloxone orders and reduced opioid prescribing when integrated into the practitioner workflow. Naloxone order rate increased from 2% in December 2018 to 13.2% in January 2019 and then continued to increase to 27.1% in December 2019. Outpatient opioid prescribing rates decreased by 15.1% per prescriber-month and total MMEs per prescriber-month decreased by 7.8%, along with other improvements in safe opioid prescribing. Adding decision support prompts to the practitioner workflow encourages safe prescribing habits and can mitigate opioid overdose risks.   Epidemiological trends in opioid-only and opioid/polysubstance-related death rates among American Indian/Alaska Native populations from 1999 to 2019: a retrospective longitudinal ecological study [OPEN ACCESS] BMJ Open Deaths due to overdoses have been increasing in the United States over the last 2 decades, but little is known about the epidemic among American Indian/Alaskan Native (AI/AN) populations. In this study the authors use the National Center for Health Statistics Mortality database to examine overdose deaths between 1999 and 2019. Overdose deaths related to opioids increased significantly over the observation period, including deaths involving other substances, notably alcohol and methamphetamines. Overall overdose mortality rates, and specifically those related to opioids in combination with alcohol or methamphetamines, have been higher among AI/AN than in other racial and ethnic groups. This study highlights inequities in access to treatment for AI/AN populations, including lack of access to medication assisted treatment for opioid use disorder.    Effects of Buprenorphine Dose and Therapeutic Engagement on Illicit Opiate Use in Opioid Use Disorder Treatment Trials [OPEN ACCESS] International Journal of Environmental Research and Public Health The authors identified 6 randomized clinical trials of buprenorphine efficacy and/or safety and performed a secondary analysis with lapse to substance use as the outcome variable. They developed a mathematical model to adjust for the effects of dose changes or missed doses during the study period (time-weighted dose). The 6 trials included 3022 participants. The mean (and median) dose was 12mg and ranged up to 32mg. Increased dose was found to be the most protective factor in preventing lapse to drug use. Also of benefit were increased interaction with clinicians and treatment center staff. The authors conclude that doses greater than that needed to prevent withdrawal are needed for maintenance treatment.     Association Between Receipt of Antidepressants and Retention in Buprenorphine Treatment for Opioid Use Disorder: A Population-Based Retrospective Cohort Study The Journal of Clinical Psychiatry This study examined the association between receiving antidepressants and retention in buprenorphine treatment. Receipt of antidepressants during buprenorphine treatment was significantly associated with reduced risk of treatment discontinuation, even after accounting for demographics, buprenorphine dosage, receipt of other psychotropic medications, co-occurring SUDs, psychiatric disorders, and pain conditions. Receiving antidepressants only prior to buprenorphine initiation was associated with an increased risk of treatment discontinuation. Using antidepressants concurrently during buprenorphine treatment is associated with improved treatment retention and highlights the importance of screening for and treating mental health disorders.   Delivering Remote Measurement-Based Care in Community Addiction Treatment: Engagement and Usability Over a 6-Month Clinical Pilot [OPEN ACCESS] Frontiers in Psychiatry Measurement-based care (MBC) is an evidence-based practice where patients routinely complete standardized measures throughout treatment to monitor clinical progress and inform clinical decision-making. This pilot study evaluated the feasibility of incorporating a digital and remotely delivered MBC system into substance use disorder (SUD) treatment within a community setting.  Patient and clinician ratings of usability and clinical utility were favorable: most patients agreed with statements that the weekly check-in was easy to navigate and aided self-reflection. All clinicians who completed usability questionnaires agreed with statements indicating that the dashboard was easy to navigate and that it provided meaningful information for SUD treatment.   Evaluation of Trends in Alcohol Use Disorder–Related Mortality in the US Before and During the COVID-19 Pandemic JAMA Network Open Alcohol sales and use have increased during the COVID-19 pandemic and in this cross-sectional study utilizing the National Vital Statistic System, the authors examine alcohol use disorder (AUD)-related mortality changes. The study looks at AUD-related mortality trends between 2012 and 2019 to project expected mortality in 2020 and 2021, which were then compared to the observed rates. The authors found a significant increase in mortality rates across all ages in 2020 (30.74%) and 2021 (28.7%) compared to projected rates. In addition, the study found the increase was most profound among those aged 25-44 (40.47% and 33.95% increases). Interventions to address the increase in AUD-related mortality should consider changes in use related to the pandemic.    Wait No Longer: Reducing Medication Wait-Times for Individuals with Co-Occurring Disorders Journal of Dual Diagnosis Community addiction treatment agencies have utilized Network for the Improvement of Addiction Treatment (NIATx) to reduce appointment wait-times. This exploratory analysis evaluated the impact of the NIATx implementation strategies on reduced wait-times to addiction, psychotropic, or both medications for individuals with co-occurring disorders (COD).  NIATx implementation strategies reduced medication encounter wait-times but timing of agency improvements varied. Despite a significant improvement, a three-week wait-time to receive pharmacological interventions is suboptimal for those with a COD in need of immediate intervention. Community addiction treatment agencies should improve medication access so that their patients “wait no longer” to receive integrated treatment for their COD.   Prehospital Buprenorphine Treatment for Opioid Use Disorder by Paramedics: First Year Results of the EMS Buprenorphine Use Pilot [OPEN ACCESS] Prehospital Emergency Care This study describes a program allowing EMS personnel to administer buprenorphine in the field to patients experiencing withdrawal (COWS>7) under the supervision of an Emergency Physician. Initial doses of 16 mg were administered and an additional 8mg were provided if needed. Substance use navigators facilitated connection with treatment and followed patient outcomes. Over the one-year trial period, 36 patients received buprenorphine. Treatment retention at seven days was 50% and 36% at 30 days. The authors conclude that EMS administered buprenorphine is feasible, safe, and has significant treatment retention at 30 days.  

Association of co-prescribing of opioid and benzodiazepine substitutes with incident falls and fractures among older adults: a cohort study [Open Access] BMJ Open  This study extracted data from Medicare records of 47,964 enrollees who were diagnosed with chronic pain and anxiety and prescribed some combination of the studied medications (opioids, benzodiazepines, gabapentinoids (GABA), or antidepressants  (SSRI/SNRI)). The outcome measure was falls or fractures. The authors note that prior research has shown opioids+benzodiazepines to be associated with high rates of falls, fractures, and deaths. These data show that opioids+GABA was associated with a greater risk of falls and fractures than opioids+benzodiazepines. An even greater risk of falls was associated with use of three or more of these medications. The authors conclude that clinicians may be underestimating the sedating effects of gabapentinoids.     Stimulant-related incident surveillance using emergency medical service records in Massachusetts, 2013–2020 Drug and Alcohol Dependence Rates of stimulant use and stimulant use disorder (StUD) have been steadily increasing, as have overdoses with stimulant use involvement. The authors examine emergency responses involving stimulants between 2013 and 2020 in Massachusetts. They categorize calls in 3 classes: class 1 – any stimulant use, class 2 – problematic stimulant use in which stimulant use was associated with acute medical or behavioral issue, and class 3 – acute stimulant-related incidents in which stimulant use was the primary issue for the call. Over the study period, calls in all 3 categories steadily increased, were more likely to be among younger adults, and the callers were more frequently male. While race/ethnicity data were frequently missing, when the data were present, Hispanic/Latinx and Black non-Hispanic patients appeared to be overrepresented among stimulant-related calls.    Trends in Prevalence of Cigarette Smoking Among US Adults With Major Depression or Substance Use Disorders, 2006-2019 JAMA This cross-sectional study assessed trends in past-month prevalence of cigarette smoking among adults with vs. without past-year major depressive episode (MDE), substance use disorders (SUDs), or both. Using data from the 2006-2019 US National Surveys on Drug Use and Health, past-month self-reported cigarette smoking prevalence declined significantly among adults with MDE from 37.3% to 24.2% (average annual percent change: −3.2), adults with SUD from 46.5% to 35.8% (average annual percent change: −1.7), and adults with co-occurring MDE and SUD from 50.7% to 37.0% (annual average annual percent change of −2.1). Prevalence declined significantly for each examined subgroup but not for American Indian or Alaskan Native with either MDE or SUDs.   Emerging Agents of Substance Use/Misuse Emergency Medicine Clinics of North America In the last decade, there has been a rise in the use of novel psychoactive substances (NPS) for recreational purposes. Many of these synthetic psychoactive substances are derived or based on older substances of abuse, but because of their novel structures, they are not easily detectable by routine immunoassay urine drug screens. Clinical effects encountered in patients using these substances depend on the substance’s structure but can be unpredictable due to the effects on various receptors at varying doses. It is important for clinicians to be aware that these novel substances exist because the diagnosis is often clinical and not based on UDS. Treatment for these substances is generally supportive and aimed at the presenting signs and symptoms.   Dopamine Supersensitivity: A Novel Hypothesis of Opioid-Induced Neurobiological Mechanisms Underlying Opioid-Stimulant Co-use and Opioid Relapse  [Open Access] Frontiers in Psychiatry Stimulants are uniquely reinforcing to persons with opioid physical dependence, contribute to the acute opioid withdrawal syndrome, and could manifest as craving and/or motivation to use, prompting opioid relapse during acute and protracted withdrawal. Current research demonstrates that changes in the dopamine system occur once physical dependence to opioids develops, the chronicity of opioid exposure is associated with a severity of changes, and dopamine deficits persist long after signs of opioid withdrawal appear to have resolved.  This review discusses how dopamine supersensitivity develops soon after opioid abstinence and results in increased response to dopamine agonists that increases in magnitude as the abstinence period continues and is evident several weeks into protracted withdrawal.     Psychological online interventions for problem gambling and gambling disorder – A meta-analytic approach Journal of Psychiatric Research In the context of the Covid-19 pandemic, this systematic review and meta-analysis investigated the effectiveness of psychological online interventions on problem gambling and gambling disorder (PGGD). Results indicate that psychological online interventions have moderate effects on PGGD in the short term. There was no indication that guided vs. unguided forms of online interventions affect the outcome. However, there is a clear trend toward unguided and even autonomous interventions which have the potential to complement or even substitute a therapist in person. Recent reviews indicate the superiority of online CBT formats compared to interventions with other theoretical backgrounds.  Toward Risk-Benefit Assessments in Psychedelic- and MDMA-Assisted Therapies | Research, Methods, Statistics JAMA Psychiatry There has been considerable attention to the evidence showing the benefits of psychedelic- and MDMA-assisted therapy. Less is known about the associated risks, primarily psychiatric, such as mood and thought disorders that sometimes outlast the acute effects of the drug and may provoke suicidal behavior. It will be important to identify patients at higher risk, for example patients with a family history of schizophrenia or bipolar disorder; however, such patients have been excluded from most clinical trials. One consideration is the implementation of risk evaluation and management strategies (REMS) but MDMA and psilocybin are already in the public domain so alternate strategies may be needed.    Implementation of a Standardized Clinical Definition of Opioid Withdrawal in the Neonate Challenges and Opportunities JAMA A standard clinical definition for neonatal abstinence syndrome (NAS) has been lacking for more than 45 years. The new definition of opioid withdrawal in the neonate includes 2 specific elements: in utero exposure to opioids with or without exposure to other psychotropic substances and the presence of 2 of 5 of the most common clinical signs of opioid withdrawal. A consistent clinical definition is essential in informing treatment protocols, administrative coding, surveillance, research criteria, and the spectrum of care for the mother-infant dyad. This could provide a significant shift in the way mothers and neonates with prenatal opioid exposure are identified, and represents a promising path forward for pregnant people and neonates with prenatal opioid exposure to improve their health and well-being

Adolescents’ and young adults’ perceptions of risks and benefits differ by type of cannabis products Addictive Behaviors Cannabis use patterns among adolescents and young adults (AYAs) have changed recently, with increasing use of non-combustible cannabis products. This survey of 433 California AYAs compared a variety of perceived risks and benefits corresponding to short-term and long-term use of combustible, blunt, vaporized, and edible cannabis, and between "ever" and "never" users. Combustible cannabis and blunts were perceived to have greater risks and benefits than vaporized/edible cannabis. The most common perceived risks were “get into trouble” and “become addicted.” The most common benefits were “feel high or buzzed” and “feel less anxious.” Ever cannabis users perceived less risks and greater benefits than never users.   Electronic cigarette use among adults in 14 countries: A cross-sectional study eClinicalMedicine Using 2015-2018 Global Adult Tobacco Survey (GATS) data, prevalence of e-cigarette use and variations by sociodemographic characteristics was examined in 14 countries. Given the progress towards a tobacco-free generation, continued surveillance of e-cigarette use is essential to developing, sustaining, and strengthening tobacco control at the country level. Approximately 18.3 million adults used e-cigarettes across these countries; higher use was observed in certain countries among men, young adults, urban residents, adults with higher education levels, and higher wealth index. Continued monitoring of e-cigarette use is critical for developing interventions and policies to prevent tobacco initiation and enhance cessation support.   Assessment of Community-Level Vulnerability and Access to Medications for Opioid Use Disorder JAMA Network Open This cross-sectional study examined the association of community vulnerability to disasters and pandemics with geographic access to each of the three Medications for Opioid Use Disorder (MOUDs) and whether this association differs by urban, suburban, or rural classification. All zip code tabulation areas (ZCTAs) within the continental U.S. were included. Median drive time to the nearest treatment location was greatest for methadone (35 [16-60] minutes) and shortest for buprenorphine (16 [0-30] minutes; P 

Show Notes:   Defining Recovery From Alcohol Use Disorder: Development of an NIAAA Research Definition  The American Journal of Psychiatry  The authors present a newly developed National Institute on Alcohol Abuse and Alcoholism (NIAAA) definition of recovery from the DSM-5 diagnosis of alcohol use disorder (AUD). This definition views recovery as a process of behavioral change and an outcome, incorporating two key components of recovery: remission from DSM-5 AUD and cessation from heavy drinking, a non-abstinent recovery outcome. It also emphasizes the importance of biopsychosocial functioning and quality of life in enhancing outcomes. By adopting a uniform definition, researchers and health care professionals can more precisely operationalize and measure recovery-related processes.     Benzodiazepine-Involved Overdose Deaths in the USA: 2000–2019  Journal of General Internal Medicine  Overdose deaths involving benzodiazepines and opioids are well studied and characterized. In this study, the authors examine all benzodiazepine-involved overdose deaths to better understand the pattern of use and overdoses between 2010 and 2019. While opioids were involved in 83.5% of all benzodiazepine related overdoses, antidepressants (18.8%), alcohol (16.3%), cocaine (13.4%) and psychostimulants (7.3%) were also frequently involved. Only 9% of benzodiazepine overdose deaths did not co-involve another substance. In addition, a larger proportion of deaths with benzodiazepine alone were due to suicide (36.2%) compared to those involving opioids (8.5%). Any interventions to reduce overdose deaths involving benzodiazepines need to consider co-involved substances and the role of suicide.    Differences in clinical features associated with cannabis intoxication in presentations to European emergency departments according to patient age and sex  Clinical Toxicology  Using presentations in the Euro-DEN Plus dataset from 2014 to 2019, this study investigated whether clinical features associated with acute cannabis intoxication in patients presenting to Emergency Departments for medical assistance differ according to patient age and sex. The most frequent clinical features in patients younger than 20 years were vomiting, reduced consciousness, and headache; and less frequently acute psychosis. Patients older than 49 years more often had hypotension and less frequently vomiting, anxiety, agitation, and reduced consciousness. Males more frequently presented with hypertension, psychosis, chest pain, and seizures.     Increased global integration in the brain after psilocybin therapy for depression  Nature Medicine  Two clinical trials assessed the subacute impact of psilocybin on brain function in treatment resistant depression. In both trials, the antidepressant response to psilocybin was rapid, sustained, and correlated with decreases in fMRI brain network modularity, implying that psilocybin’s antidepressant action may depend on a global increase in brain network integration. Network cartography analyses indicated that 5-HT2A receptor-rich higher-order functional networks became more functionally interconnected and flexible after psilocybin treatment. Consistent efficacy-related brain changes, correlating with robust antidepressant effects across two studies, suggest an antidepressant mechanism for psilocybin therapy: global increases in brain network integration.    Non–prescribed buprenorphine preceding treatment intake and clinical outcomes for opioid use disorder  Journal of Substance Abuse Treatment  In this study, data were obtained from a large, multi-site, multi-state office-based opioid treatment (OBOT) network. Individuals (n=971) were randomly selected from a pool of 18,513 initiating buprenorphine care. At treatment entry, 60% tested positive for buprenorphine (TPB), and 73% of these were taking non-prescribed buprenorphine. The TPB group was less likely to test positive for opiates at treatment entry (25% vs. 53%) and continued to be less likely to test positive for opiates during the first several months of treatment. The TPB group was less likely to discontinue treatment (hazard ratio 0.52). There were no significant differences comparing those prescribed with non-prescribed use, in the TPB group. They suggest that use of “diverted” buprenorphine is a marker of patient motivation for treatment and conclude that “concerns regarding buprenorphine diversion due to misuse may be misplaced.”      What are the implications of the steady 40 year rise in US fatal overdoses?: Introduction to a special section  International Journal of Drug Policy  While overdose deaths due to opioids is understood to be the driver of current increase in overdose deaths and a well-recognized epidemic, in a series of recent studies it was demonstrated that overdose deaths have been steadily increasing over the last 40 years.  In this editorial, the authors discuss various commentaries responding to these studies and highlight various perspectives on these data. While much of the focus in recent years has been on opioid overdose deaths and access to medication assisted treatment, interventions may be needed to address broader factors associated with substance use, including both supply and demand side factors. In addition, data at more local levels may be useful in predicting substance use epidemics at more local levels for intervention.     The Effectiveness of Exercise as an Adjunct Intervention to Improve Quality of Life and Mood in Substance Use Disorder: A Systematic Review  Substance Use and Misuse  This review examined 42 papers (2531 individuals) regarding the effect of exercise on quality of life, depression, and anxiety during treatment of substance use disorder. The majority, 22 studies, took place in an inpatient rehabilitation setting. They examined a broad range of exercise modalities: aerobic, resistance, flexibility, tai chi, yoga, high intensity interval training, and increasing step count. The results support a beneficial impact of exercise on quality of life, depression, and anxiety. There was a dose response effect with greater benefit with increased number of sessions per week and over 12 weeks of program duration, however, some improvement was seen following a single session. The modality of exercise was less important and simply increasing daily step count was beneficial.      Addressing the substance use treatment gap in Africa using digital screening and brief interventions  The Lancet Psychiatry  Services and staffing for substance use treatment and prevention are scarce throughout many parts of Africa. One treatment option is a self-administered digital substance use screening and brief intervention (SBI). This literature search noted a paucity of research investigating the feasibility of SBIs in Africa. Such an SBI has the potential to increase access to care and decrease intervention delivery costs. Given the rapid increase in internet penetration rates, and smartphone usage across the continent, as well as limited access to treatment, there is an urgent need to explore the utility of this treatment tool across the continent. 

Show Notes:     Association of Medication Treatment for Opioid Use Disorder With Suicide Mortality The American Journal of Psychiatry  This study evaluated whether medications for opioid use disorders (MOUD) are associated with reduced risk of suicide mortality and compared different agents. Data were collected for 61,633 veterans (93% male) receiving MOUD. Approximately half received buprenorphine and a quarter received methadone or naltrexone (oral or extended-release).  The hazard ratio (HR) for suicide mortality while on MOUD was 0.45 and for all-cause mortality, it was 0.34. Stopping MOUD increased the risk for suicide (HR = 1.47) and all-cause mortality (HR = 1.14). Buprenorphine reduced suicide mortality (HR = 0.34) whereas naltrexone did not (HR = 1.28). Buprenorphine reduced all-cause mortality (HR = 0.27) to a greater extent than naltrexone (HR = 0.64), while results with methadone were less clear. Overall, MOUD produced dramatic reductions in both suicide and all-cause mortality with the effect most pronounced for buprenorphine. Naltrexone, however, did not reduce suicide mortality.      Research and Science  Fetal Exposure to Cannabis and Childhood Metabolic Outcomes: The Healthy Start Study  The Journal of Clinical Endocrinology & Metabolism This study investigated whether fetal exposure to cannabis is associated with increased adiposity and markers of impaired glucose homeostasis in early childhood. Approximately 15% of mothers had detectable levels of any cannabinoid at ~27 weeks’ gestation, indicating fetal exposure to cannabis. Fetal exposure to cannabis was associated with increased adiposity and fasting glucose in early childhood. This study further supports discouraging women from using any cannabis while pregnant or breastfeeding to minimize adverse health effects on the offspring.   Trends in seizures of powders and pills containing illicit fentanyl in the United States, 2018 through 2021  Drug and Alcohol Dependence Fentanyl continues to be a leading cause of overdose in the United States and is increasingly found in counterfeit prescription pills. This study examines trends in pills containing fentanyl using the national seizure data from High Intensity Drug Trafficking Areas between January 2018 and December 2021. There was a significant increase in both fentanyl-containing powder seizures (424 to 1539) and pill seizures (68 to 635) during the study period. In addition, the proportion of seizures that were pills increased (13.8% to 29.2%) and the number of pills seized increased (42,202 to 2,089,186). While the presence of fentanyl in heroin supply is more widely known, its presence in pills poses a potential risk that is not as widely disseminated, resulting in the need for public education.    Beliefs and Characteristics Associated With Believing Nicotine Causes Cancer: A Descriptive Analysis to Inform Corrective Message Content and Priority Audiences Nicotine and Tobacco Research In this study, authors examine cigarette smokers’ perceptions about harm from tobacco, specifically nicotine as the source of harm. The authors found that a significant proportion of smokers (61.2%) believed that nicotine was the source of cancer risk or were not sure. This belief was more common among non-Hispanic Black and Hispanic smokers as well as those with low incomes. Smokers with high school or higher education were less likely to believe nicotine was the source of the risk. In addition, those who had used a non-combustible tobacco product, including electronic cigarettes, were less likely to have this perception. The misperception about the risk of nicotine may impact smokers’ behavior, and switching to less harmful products and education is needed to correct this commonly held belief.     Effect of Medical Marijuana Card Ownership on Pain, Insomnia, and Affective Disorder Symptoms in Adults JAMA Network Open This randomized clinical trial involving 186 participants examined the risks and benefits of obtaining a medical marijuana card for adults who seek medical marijuana for pain, insomnia, and anxiety or depressive symptoms. Immediate acquisition of a medical marijuana card increased the incidence and severity of cannabis use disorder (CUD) and resulted in no significant improvement in pain, anxiety, or depressive symptoms, but improved self-reported sleep quality. Findings suggest the need for further investigation into the benefits of medical marijuana card ownership for insomnia symptoms and the risk of CUD, particularly for those with anxiety or depressive symptoms.   Learn More Burst Suppression Electroencephalography (EEG) Pattern with Coma and Loss of Brain Stem Reflexes Following a Baclofen Overdose with Subsequent Full Recovery  American Journal of Case Reports Baclofen toxicity can present both clinically and with EEG abnormalities consistent with anoxic brain injury, suggesting an inevitable progression to brain death. This is a case report of a middle-aged woman found unresponsive who presented with apnea, loss of rudimentary neurologic findings on physical exam, burst suppression EEG findings, and a prolonged comatose state for nearly 48 h, followed by rapid resolution of symptoms secondary to a supratherapeutic baclofen ingestion. When provided with appropriate supportive care and prolonged observation, improvement with full neurologic recovery is often seen despite the initial grim clinical picture.   Against Our Instincts: Decriminalization of Buprenorphine Journal of the American Board of Family Medicine In this commentary the authors make a case for the decriminalization of the possession of buprenorphine. The authors cite the dramatic reduction in mortality (by 2/3 in one meta-analysis) with buprenorphine treatment. According to data from Tennessee, buprenorphine has little risk of overdose when used alone. A meta-analysis indicated that diverted buprenorphine was used for therapeutic rather than recreational purposes. Many have difficulty accessing buprenorphine due to a lack of providers and economic barriers, and the authors note that when a Vermont county decided not to prosecute possession of buprenorphine (along with other measures to increase access) the overdose rate reduced by 50% while increasing in the rest of the state. The authors conclude that the benefits of decriminalizing buprenorphine possession outweigh the risks.