Opioid Discontinuation Research Articles

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

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

Risk factors and outcomes of pediatric non-invasive respiratory support failure in Latin America

BackgroundNoninvasive respiratory support (NRS) is standard in pediatric intensive care units (PICUs) for respiratory diseases, but its failure can lead to complications requiring invasive mechanical ventilation (IMV). This study aimed to identify risk factors for NRS failure in children with acute respiratory failure (ARF) in PICUs, and compare complications and outcomes between IMV-only and NRS failure patients. MethodsWe conducted a cohort study using data from the LARed Network prospective registry (April 2017–November 2022), in children under 18 years admitted to PICUs for ARF. Cases were divided into subgroups: those managed with IMV only, those who experienced NRS failure requiring IMV, those who received NRS successfully, and those who did not require NRS or IMV. Exclusions included patients with home respiratory support prior to admission and those with incomplete data. Multivariate mixed models analyzed NRS failure risk factors, and complications between the IMV-only and NRS failure groups, using centers as a random effect. ResultsA total of 7374 children met the inclusion criteria, with 6208 in the NRS group and 1166 in the IMV-only group. The NRS success rate was 85.3 %. Risk factors for NRS failure included age (median of 4.6 months, interquartile range of 2.1–14.2 months), history of prematurity (adjusted odds ratio [aOR]=1.53, 95 % confidence interval [CI]: 1.20 to 1.95) or malnutrition (aOR=1.85, 95 % CI: 1.18 to 2.91), suspected bacterial infection (aOR=5.12, 95 % CI: 4.05to 6.49), FiO2 >30 % (aOR=1.52, 95 % CI: 1.18 to 1.97), severe hypoxemia with SpO2/FiO2 ≤150 (aOR=1.85, 95 % CI: 1.48 to 2.30), tachypnea (aOR=1.42, 95 % CI: 1.18 to 1.72), tachycardia (aOR=1.77, 95 % CI: 1.47 to 2.12), and lung consolidations (aOR=1.45, 95 % CI: 1.14 to 1.85) or interstitial infiltrates (aOR=1.29, 95 % CI: 1.05 to 1.58) on chest X-ray. There were no significant differences in morbidity, mortality, duration of IMV, or PICU length of stay between patients who received IMV only and those who experienced NRS failure. However, patients who experienced NRS failure were more likely to develop withdrawal symptoms related to sedative or opioid discontinuation and/or delirium (aOR=2.57, 95 % CI: 1.85 to 2.57). ConclusionThis study identified key risk factors for predicting NRS failure in children with acute ARF in PICUs, including younger age, prematurity, malnutrition, suspected bacterial infection, FiO2 >30 %, severe hypoxemia (SpO2/FiO2 ≤150), tachypnea, tachycardia, and radiological findings such as lung consolidation and interstitial infiltrates. Compared to patients managed with IMV from the start, those who experienced NRS failure were more likely to develop withdrawal symptoms and/or delirium, although clinical outcomes such as mortality, IMV duration, and PICU length of stay were similar in both groups.

AN UPDATED VIEW ON THE INFLUENCE OF INITIAL OPIOID PRESCRIPTION CHARACTERISTICS ON LONG-TERM OPIOID USE AMONG OPIOID NAÏVE PATIENTS

OBJECTIVESThis retrospective cohort study provides an updated view on the association between the likelihood of long-term opioid use (LTOU) and characteristics of the initial opioid prescription (dose, opioid type) and initial opioid prescription episode (days’ supplied) among opioid-naïve patients utilizing IQVIA PharMetrics®Plus for Academics database representative of commercially insured patients in the US. METHODSKaplan-Meier estimates were used to determine opioid continuation likelihood at 365 days stratified by the characteristics of the initial opioid prescription and initial opioid prescription episode. Cox-proportional hazard models were estimated to determine the strength of association between initial opioid prescription characteristics and opioid continuation. RESULTSA total of 578,403 cancer-free, SUD-free, opioid-naïve subjects aged ≥14 years that filled ≥1 opioid prescriptions between April 13, 2016 and April 18, 2020 were identified and categorized based on time to opioid discontinuation. After accounting for censoring, 5.05% of persons continued opioid use for ≥365 days. Compared to a 1-2 days’ supply (DS), the likelihood of opioid discontinuation was consistently lower with higher DS [HRs (CIs): 3–4 days' supply = 0.66 (0.65-0.66); 5–7 DS = 0.41 (0.41-0.41); 8–10 DS = 0.33 (0.33-0.34); 11–14 DS = 0.30 (0.29-0.31); 15–21 DS = 0.26 (0.26-0.27); ≥22 DS = 0.17 (0.17-0.18)]. These associations between increased DS and decreased likelihood of discontinuing opioid remained consistent across different pain etiologies. CONCLUSIONSIn this era of more conservative opioid prescribing, increases in DS remains the strongest factor associated with a higher likelihood of LTOU.

Chronic Opioid Use Following Implementation of Oregon's Medicaid Back Pain Policy

IntroductionIn 2016, Oregon developed an innovative policy to improve care for Medicaid patients with back pain. The objective of this study was to identify factors associated with dose reduction and discontinuation among Medicaid patients using chronic opioid therapy following implementation of this policy. MethodsUsing Medicaid administrative claims data, this was a retrospective cohort of patients on chronic stable opioid therapy between July and December 2016. Outcomes assessed were 1) 30% reduction in opioid dose and 2) an absolute discontinuation between January to December 2017. Multivariable logistic regressions evaluated association between dose reduction outcomes and clinical and demographic factors. ResultsOf 4,643 Medicaid patients on chronic opioid therapy, 3853 (83%) had a dose reduction and 651 (14%) discontinued opioids; patients with back pain were more likely to have a dose reduction (adjusted odds ratio [aOR] 1.19; 95% 1.01 to 1.41). Factors associated with discontinuation included having a mental health diagnosis (aOR 1.30; 95% CI 1.08 to 1.56), substance use disorder (aOR 1.90; 95% CI 1.41 to 2.56), opioid use disorder (aOR 1.55; 95% CI 1.21 to 1.99), and receipt of buprenorphine (aOR 2.82; 95% CI 1.30 to 6.15). Discontinuation was less likely in Black patients (aOR 0.50; 95% CI 0.29 to 0.85), in older age groups, and in those with a higher opioid dose at baseline. ConclusionsMost Medicaid beneficiaries had a dose reduction following implementation of Oregon's back pain policy. Opioid discontinuation was associated with factors that suggest providers pursue this strategy for patients at higher overdose risk.

Opioid tapering and discontinuation for head and neck cancer (HNC) survivors.

366 Background: Older HNC survivors often experience post-treatment pain, and they fill opioid prescriptions more often than similar cancer-free adults for the first 5 years after HNC diagnosis. To better understand whether ongoing opioid use is likely explained by continued opioid prescribing from the time of cancer treatment, we aimed to quantify the extent to which opioids prescribed near the end of treatment are reduced in dose (tapered) and discontinued after treatment completion. Methods: Using linked Surveillance, Epidemiology, and End Results (SEER) registry and Medicare claims data, we identified adults age >65 diagnosed 2014-2017 with stage I-III HNC with ≥6 months treatment-free follow-up prior to censoring at further treatment, new cancer, hospice, 3 months prior to death, or end 2019. We evaluated the presence of a new or ongoing opioid prescription 2 weeks following treatment completion (baseline) and calculated daily baseline dose in morphine milligram equivalents (MME). Among those with an opioid prescription (“on opioids”) at baseline, we described cross-sectional metrics of opioid receipt and dose every 30 days: proportion of survivors on opioids (who were also on opioids the prior month), initial and current dose of opioids for those currently on opioids, and proportion of survivors on opioids whose dose declined ≥50% from baseline. Results: Among 5135 HNC survivors, 894 were on opioids at baseline (average daily dose 44 MME). By 1 month, 29% of survivors on opioids at baseline (N=260) had a current opioid fill, and 7% had an opioid dose <50% of the baseline dose. Discontinuation of opioids increased each month; median daily dose each month ranged from 44 MME at 30 days to 60 MME at 180 days. Those who remained on opioids over 6 months had the highest opioid dose than those who discontinued earlier (median 45 MME at 90 days; Table). Conclusions: About 1 in 6 HNC survivors had an opioid prescription filled at the end of cancer treatment, and opioids were generally discontinued within a few months. Given the low median dose at baseline, the limited evidence of tapering likely results from low initial opioid doses rather than a failure to taper from long-term or high-dose use. Opioid use among older treatment-free HNC survivors that is apparent years after treatment completion is unlikely to result from inadequate tapering. Instead, it may be due to new or worsening cancer-related pain, as well as to non-cancer pain. Dose reduction and discontinuation (N=894). Days after baseline Off opioids On opioids Starting dose in MME among those on opioids Current dose in MME among those on opioids Tapered to <50% starting dose N (%) N (%) Median (IQR) Median (IQR) N (%) 30 634 (71) 260 (29) 53 (30, 80) 44 (29, 60) 61 (7) 60 772 (86) 122 (14) 45 (30, 67.5) 44 (29, 60) 15 (2) 90 820 (92) 74 (8) 58 (30, 90) 45 (29, 60) 7 (1) 120 838 (94) 56 (6) 60 (30, 90) 45 (25, 60) 7 (1) 150 849 (95) 45 (5) 56 (30, 65) 48 (29, 60) 2 (<1) 180 856 (96) 38 (4) 51 (30, 65) 60 (30, 90) 1 (<1)

Efficacy of transdermal buprenorphine patch for managing withdrawal symptoms in patients with cancer physically dependent on prescription opioids.

The physical dependence on prescription opioids among cancer survivors remains an under-investigated area, with a scarcity of well-designed prospective studies. This single-arm, phase-2 clinical trial in Korea assessed the efficacy and safety of a transdermal buprenorphine patch (TBP) in managing physical dependence on prescription opioids in cancer survivors, as confirmed through the DSM-5 criteria or psychiatric consultation for opioid withdrawal. This study involved a 4-phase treatment protocol of screening, induction/stabilization, discontinuation, and monitoring. The primary outcome was the rate of successful opioid discontinuation, as measured by a negative urine-drug screening at 8 weeks. Key secondary outcomes included the resumption of prescribed opioids, changes in both the Clinical Opioid Withdrawal Scale (COWS) and morphine equivalent daily dose (MEDD), and assessments related to the psychological and physiological aspects of dependence and safety. Thirty-one participants were enrolled. In the intention-to-treat population, the success rate of opioid discontinuation was 58%, with only 2 participants experiencing a resumption of prescribed opioids. Significant reductions were observed in MEDD, which decreased from 98 to 26mg/day (P < .001), and COWS scores, which decreased from 5.5 to 2.8 (P < .001). Desire to use opioids reduced from 7.0 to 3.0 on a 10-point numeric rating scale (P < .001). Toxicities related to TBP were mild and manageable, without severe precipitated withdrawal symptoms. TBP may be considered as an alternative therapeutic option in cancer survivors physically dependent on prescription opioids, especially where sublingual formulations are unavailable.

Dangerous Variation or Patient-Centered Care? Palliative Care and Pain Providers' Comfort, Experiences, and Approaches when Treating Cancer Pain With Coexisting Aberrant Behaviors.

Patients with cancer-related pain are at high risk for aberrant drug use behaviors (ADB), including self-escalation, diversion and concurrent illicit substance or opioid misuse; however, limited evidence is available to guide opioid prescribing for patients with life-limiting illness and concurrent or suspected ADB. We sought to characterize how specialists evaluate for and manage these high-risk behaviors in patients with cancer-related pain. We conducted telephonic semi-structured interviews with palliative care and pain medicine providers. Participants discussed their own comfort and experience level with identifying and managing ADB in patients with life-limiting illness. They were subsequently presented with a series of standardized scenarios and asked to describe their concerns and management strategies. 95 interdisciplinary pain and palliative care specialists were contacted; 37 agreed to participate (38.9%). Analysis of interview contents revealed several central themes: (1) widespread discomfort and anxiety regarding safe and compassionate opioid prescribing for high-risk patients, (2) belief that widely used risk-mitigation tools such as opioid contracts and urine drug screens provided inadequate support for decision-making, and (3) lack of institutional and organizational support and guidance for safe prescribing strategies. Most clinicians reported self-education regarding addiction and alternative prescribing/pain management strategies. Providers varied widely in their willingness to discontinue opioid prescribing in a patient with aberrant behavior and pain associated with life-limiting illness. Providers caring for patients demonstrating ADB and cancer-related pain struggle to balance safe prescribing with symptom management. Increased guidance is needed regarding opioid prescribing, monitoring, and discontinuation in high-risk patients.

Clinical and healthcare use outcomes after cessation of long term opioid treatment due to prescriber workforce exit: quasi-experimental difference-in-differences study

ABSTRACTObjectiveTo examine the association between prescriber workforce exit, long term opioid treatment discontinuation, and clinical outcomes.DesignQuasi-experimental difference-in-differences studySetting20% sample of US Medicare beneficiaries, 2011-18.ParticipantsPeople receiving long term opioid treatment whose...

Long-Term Reductions in Opioid Medication Use After Spinal Stimulation: A Claims Analysis Among Commercially-Insured Population.

Chronic, non-cancer pain significantly and negatively impacts patient quality of life. Neuromodulation is a major component of multi-modal interdisciplinary approaches to chronic pain management, which includes opioid and nonopioid medications. In randomized controlled trials, spinal cord stimulation (SCS) has been shown to reduce pain and decrease short-term opioid use for patients. This study sought to evaluate the effect of SCS on longer term opioid and non-opioid pain medication usage among patients over ≥3 years of follow-up. Claims analysis was conducted using the Merative™ MarketScan® Commercial Database. Patients aged ≥18 who initiated SCS between 1/1/2010 and 3/31/2021 with ≥1 year of baseline data and ≥3 years of follow-up data were included. Opioid discontinuation, daily dose (DD) reduction, proportion of days covered (PDC), concomitant co-medication with benzodiazepines and/or gabapentinoids, and polypharmacy were evaluated during the baseline and follow-up periods. Adjusted logistic regression was used to evaluate the impact of baseline dosages on discontinuation and dose reduction. During follow-up, 60% of 2,669 SCS patients either discontinued opioid use or reduced opioid DD by at least 20% from baseline; another 15% reduced DD by 1-19%. Logistic regression showed patients with higher baseline dosages were less likely to discontinue opioids completely (odds ratio[OR] 95% confidence intervals[CI]: 0.31[0.18,0.54]) but more likely to reduce their daily dose (OR[CI]: 7.14[4.00,12.73], p<0.001). Mean PDC with opioids decreased from 0.58 (210 of 365 days) at baseline to 0.51 at year 3 (p<0.001). With SCS, co-medication with benzodiazepines decreased from 47.3% at baseline to 30.3% at year 3, co-medication with gabapentinoids reduced from 58.6% to 42.2%, and polypharmacy dropped from 15.6% to 9.6% (all p<0.001). Approximately three-quarters of patients who received SCS therapy either discontinued or reduced systemic opioid use over the study period. SCS could assist in reducing long-term reliance on opioids and other pain medications to treat chronic non-cancer pain.

Outcome in methadone maintenance treatment of immigrants from the former Union of Soviet Socialist Republics

ContextImmigrants from the former Union of Soviet Socialist Republics (USSR) are more prevalent in Methadone maintenance treatment (MMT) in Israel than their percentage in the general population.AimsTo compare their characteristics and outcomes to those of Israeli-born and other immigrant patients.MethodsRetention and survival since admission (June/1993–Dec/2022) until leaving treatment (for retention), or at the end of follow-up were analyzed. Vital data was taken from a national registry. Predictors were estimated using Kaplan–Meier and Cox regression models.ResultsThe USSR patients (N = 262) compared with other immigrants (N = 132) and Israeli-born (N = 696) were more educated (≥ 12y) (p < 0.001), admitted to MMT at a younger age (p < 0.001), following a shorter duration of opioid usage (p < 0.001). More of them ever injected drugs (p < 0.001) and ever drank alcohol (p < 0.001). One-year retention was comparable (77.2% vs. 75.6% and 72%, p = 0.2) as did opioid discontinuation in those who stayed (p = 0.2). Former USSR patients had longer cumulative retention of their first admission (p = 0.05) with comparable overall retention since first admission, and survival, although the age of death was younger. Specific origin within the former USSR found immigrants from the Russian Federation with the best outcome, and those from Ukraine as having high HIV seropositive and shorter retention.ConclusionsDespite several characteristics known to be associated with poor outcomes, former USSR immigrants showed better adherence to MMT, reflected by their longer cumulative retention in their first admission, lower rate of readmissions, and a comparable survival and overall retention in treatment. An in depth study is needed in order to understand why they decease at a younger age.

The association of pain impact and sleep disruption with opioid withdrawal during opioid-use disorder treatment.

Persons with opioid-use disorder (OUD) often experience opioid withdrawal and opioid craving, which can drive continued opioid use and treatment discontinuation. In addition, hyperalgesia is common among persons with OUD, yet few studies have examined the role of pain impact during OUD treatment. The purpose of the present study was to test whether opioid withdrawal and craving were elevated in the context of greater pain impact (i.e. greater pain intensity and interference), and whether these associations changed throughout treatment. Participants in residential OUD treatment (n= 24) wore wrist actigraphy to measure sleep and completed daily measures of pain impact, opioid withdrawal and opioid craving for up to 28 days. Mixed effects models were used to examine whether daily elevations in pain impact and sleep continuity were associated with withdrawal severity and opioid craving. Elevations in withdrawal, but not craving, occurred on days when individuals reported higher scores on the pain impact scale. Associations between pain impact and withdrawal were present throughout treatment, but stronger during early treatment. In contrast, both withdrawal and opioid craving were elevated following nights of greater wake after sleep onset and awakenings, but these findings were often more pronounced in early treatment. Pain impact and sleep disturbance are 2 factors associated with opioid withdrawal and opioid craving. Novel pharmacotherapies and scalable adjunctive interventions targeting sleep and pain impact should be tested in future work to improve OUD treatment outcomes.

Healing journey: Experiences of First Nations individuals with recovery from opioid use.

To understand experiences of recovery from opioid use among First Nations individuals living in a small remote community. Qualitative phenomenologic study. Northwestern Ontario. Sixteen First Nations individuals living in a remote community who had participated in or completed the community opioid agonist therapy program. Extensive community consultation took place to ensure local acceptance of the study and permission for publication. Semistructured telephone interviews with consenting participants were audiorecorded between November and December 2021 and transcribed. Transcripts were reviewed and discussed in meetings with Indigenous and non-Indigenous research team members who conducted thematic analysis using immersion and crystallization. Participants described their opioid use as a form of self-management of trauma. Their recovery processes were multifaceted and included developing cultural and self-awareness. Motivation for change often arose from concerns about family well-being and finances. Traditional cultural practices and time spent on the land were identified as important wellness experiences. Barriers to healing included limited clinical and holistic addiction services, particularly around dose weaning and opioid agonist therapy discontinuation. Community-based addiction programming for First Nations patients needs to be robust. It requires resources for trauma-informed clinical and addiction care, culturally appropriate addictions education, aftercare support, and land-based activities.

Low dose lofexidine for medically directed outpatient opioid tapering in adults with chronic pain: a prospective case series

BackgroundIn adults with chronic pain, mild-to-moderate withdrawal symptoms during medically directed opioid tapering in the outpatient setting may not be accompanied by hypertension or tachycardia. This clinical scenario could limit the use of lofexidine at dosages reported in clinical trials of opioid withdrawal precipitated by abrupt opioid discontinuation. Thus, the primary aim of this prospective case series is to describe the use of low dose lofexidine for opioid withdrawal in patients with chronic pain undergoing medically directed opioid tapering in an outpatient setting.MethodsSix patients (white 5, Latino 1) admitted to an outpatient interdisciplinary pain rehabilitation program met inclusion and exclusion criteria. Patients self-selected to undergo medically directed opioid tapering, and the medication the patients were prescribed upon admission was used in the taper schedule. Upon initiation of the opioid taper, patients received 0.18 mg of lofexidine every 6 hours. ResultsFive of the six patients were women, and the median morphine milligram equivalents at baseline were 36.9. The median taper duration was 15 days, and the median duration of lofexidine administration was 14 days. Withdrawal scores were mild throughout the taper in four patients, and two patients with fibromyalgia experienced single episodes of moderately severe withdrawal symptoms at the median morphine milligram equivalent midpoint of the taper. No hypotension or sustained bradycardia were observed, and no adverse effects related to lofexidine were reported.ConclusionThe observations from this prospective case series suggest that low-dose lofexidine may be a feasible adjunct medication to attenuate withdrawal symptoms in adults with chronic pain undergoing outpatient opioid tapering.

Patient Motivation to Reduce or Discontinue Opioids for Chronic Pain: Self-efficacy, Barriers, and Readiness to Change.

This study aimed to assess levels and predictors of self-efficacy and motivation to change opioid use among a community sample of patients using opioids for chronic pain, as well as patient-reported barriers to pursuing opioid discontinuation. Participants with a variety of chronic pain conditions, recruited from ResearchMatch.org , completed a battery of electronic, self-report questionnaires assessing demographic and medical characteristics, pain treatment history, and levels of readiness, self-efficacy, and other attitudes toward reducing or discontinuing opioid use. Multiple regression analyses and analyses of variance were conducted to examine predictors of readiness and self-efficacy to change opioid use. A modified version of rapid qualitative analysis was utilized to analyze themes in participant responses to an open-ended item about "what it would take" to consider opioid discontinuation. The final sample included N=119 participants, the majority of whom were female (78.2%), Caucasian (77.3%), and well-educated. Readiness and self-efficacy to decrease or stop opioid use were fairly low on a 0 to 10 Visual Analog Scale (2.6 to 3.8) and significantly higher to decrease than stop ( P <0.01). Higher readiness to change was predicted by lower pain severity and higher concern about opioids, whereas higher self-efficacy was predicted by shorter pain duration. Results from the qualitative analyses revealed that the availability of an alternative treatment option was the most commonly cited requirement to consider opioid discontinuation. Patients with lower pain severity, shorter duration of pain, and higher concerns about opioids may be a prime target from a motivation standpoint for interventions addressing opioid tapering and discontinuation.

Neuroplasticity of the extended amygdala in opioid withdrawal and prolonged opioid abstinence.

Opioid use disorder is characterized by excessive use of opioids, inability to control its use, a withdrawal syndrome upon discontinuation of opioids, and long-term likelihood of relapse. The behavioral stages of opioid addiction correspond with affective experiences that characterize the opponent process view of motivation. In this framework, active involvement is accompanied by positive affective experiences which gives rise to "reward craving," whereas the opponent process, abstinence, is associated with the negative affective experiences that produce "relief craving." Relief craving develops along with a hypersensitization to the negatively reinforcing aspects of withdrawal during abstinence from opioids. These negative affective experiences are hypothesized to stem from neuroadaptations to a network of affective processing called the "extended amygdala." This negative valence network includes the three core structures of the central nucleus of the amygdala (CeA), the bed nucleus of the stria terminalis (BNST), and the nucleus accumbens shell (NAc shell), in addition to major inputs from the basolateral amygdala (BLA). To better understand the major components of this system, we have reviewed their functions, inputs and outputs, along with the associated neural plasticity in animal models of opioid withdrawal. These models demonstrate the somatic, motivational, affective, and learning related models of opioid withdrawal and abstinence. Neuroadaptations in these stress and motivational systems are accompanied by negative affective and aversive experiences that commonly give rise to relapse. CeA neuroplasticity accounts for many of the aversive and fear-related effects of opioid withdrawal via glutamatergic plasticity and changes to corticotrophin-releasing factor (CRF)-containing neurons. Neuroadaptations in BNST pre-and post-synaptic GABA-containing neurons, as well as their noradrenergic modulation, may be responsible for a variety of aversive affective experiences and maladaptive behaviors. Opioid withdrawal yields a hypodopaminergic and amotivational state and results in neuroadaptive increases in excitability of the NAc shell, both of which are associated with increased vulnerability to relapse. Finally, BLA transmission to hippocampal and cortical regions impacts the perception of conditioned aversive effects of opioid withdrawal by higher executive systems. The prevention or reversal of these varied neuroadaptations in the extended amygdala during opioid withdrawal could lead to promising new interventions for this life-threatening condition.

Risks still prevail from abrupt discontinuation of opioids for pain

Newly released data for opioid pain treatment episodes during the 2014–2020 period suggest that while the dangerous practice of abrupt discontinuation of high‐dose opioids slowed over that time, its overall prevalence remains a concern. The findings of the cohort study also revealed that men and Black patients are most susceptible to this practice, suggesting yet another disparity in access to high‐quality medical care.

Generalized myoclonus restricted to the “Smack” withdrawal state: A rare case report

Myoclonus is regarded as a direct neurotoxic effect of opioid metabolites. It is seen less frequently in conjunction with opioid discontinuation (opioid withdrawal myoclonus [OWM]). Only a few case reports from palliative medicine and anesthesia have highlighted the development of OWM. We report an unusual case of a 35 years old, opioid-dependent (smack) adult male who developed abnormal involuntary jerky movements of limbs and torso in the withdrawal phase. There was no change in the level of consciousness. The neurological examination as well as serum biochemistry was normal. The electroencephalogram showed no epileptiform activity. The patient was started on oral substitution therapy (tramadol 150 mg/day) after which abnormal movements subsided within 72 h. We conclude that myoclonus can be a part of opioid withdrawal. Appropriate recognition of its benign nature and psycho-education to patients and families shall foresee better outcomes.

Abstract 16368: Opioid Withdrawal-Induced Takotsubo Cardiomyopathy in Hypertrophic Cardiomyopathy

Introduction: This case highlights opioid withdrawal-induced Takotsubo cardiomyopathy (TCM) in a patient with pre-existing hypertrophic cardiomyopathy (HCM) and discusses the concurrent management. Clinical Presentation: An 85-year-old female with HCM, depression, and chronic back pain presented with generalized weakness five days after opioid discontinuation. She exhibited elevated troponin levels and ST elevation in anteroseptal leads, concerning for STEMI. Coronary angiogram revealed nonobstructive coronary artery disease. Transthoracic echocardiogram revealed newly reduced EF 45%, hyperdynamic basal left ventricle, and akinetic mid-distal left ventricle, consistent with TCM. Notably, marked basal anteroseptum thickness and systolic anterior mitral valve motion with left ventricular outflow tract obstruction (LVOTO) and a peak gradient of 92 mmHg. Presentation was complicated by hypotension, pulmonary edema and cardiorenal syndrome. β-blocker use initially deferred, opting for phenylephrine and diuresis until stabilization permitted β-blocker introduction. Discussion: We present a unique case of TCM precipitated by opioid withdrawal in a patient with existing HCM. Standard critical care management for TCM involves hemodynamic support until cardiac function recovers, though the use of vasopressors and inotropes remains controversial. Importantly, this case demonstrates severe provoked LVOTO, mimicking acute myocardial ischemia. Recognizing such scenarios is vital, as inappropriate use of vasodilators or inotropes can be fatal. Class I-IIa recommendations endorse β-blockers and vasoconstrictors for severe provoked LVOTO with hypotension and pulmonary edema. Phenylephrine, a selective α-agonist, maintains LVOT turgidity through preload enhancement, while β-blockers facilitate ventricular filling and reduce LVOT pressure gradient. Further research is warranted as current evidence level remains class C.

Opioid tapering and mental health crisis in older adults.

Opioid tapering and discontinuation have increased in recent years with the implementation of national prescribing guidelines. This study aimed to examine the relationship between opioid tapering velocity and mental health crisis events in older Medicare beneficiaries. A nested case-control study was conducted using the 2012-2018, 5% national Medicare claims data. Older adults with chronic non-cancer pain (CNCP) who were receiving long-term opioid therapy (LTOT) were included in the study. Cases were defined as individuals experiencing mental health crisis events; controls were identified using incidence density sampling. The opioid tapering velocity was measured in the 120-day hazard period that yielded a monthly percentage of dose change. Conditional logistic regression was used to assess the relationship of interest. A total of 42 091 older adults with CNCP were eligible for the study. Cases (n = 952) were matched with controls in a 1:2 ratio based on age (±1 year) and time of cohort entry (±30 days). A higher percentage of controls (67.65%) were on steady dose compared with cases (59.03%). In the adjusted model, tapering (aOR = 1.36; 95% CI: 1.02-1.83), rapid tapering (aOR = 1.45; 95% CI: 1.11-1.91), and dose escalation (aOR = 1.78; 95% CI: 1.32-2.39) were significantly associated with the mental health crisis, compared with steady dose. Both opioid tapering and dose escalation are associated with mental health crisis events. Patient-driven and gradual dose tapering, as recommended by prescribing guidelines, should be promoted to prevent mental health crisis events among older adults on LTOT.

A pharmacist-led opioid de-escalation program after completion of chemoradiotherapy in locally advanced head and neck cancer.

Persistent opioid use frequently leads to substantial negative impacts on quality of life, and as the outlook for numerous cancer types continues to improve, these complications become increasingly crucial. It is essential to acknowledge that extended or excessive opioid use may result in adverse effects in patients who completed radiation therapy (RT). In this time-series analysis, we compared the outcomes of patients who participated in the pharmacist-led opioid de-escalation (PLODE) program after completing concurrent radiotherapy (CRT) between June 2018 and February 2019 against patients who completed CRT between June 2017 and March 2018 and did not participate in the program. Among 61 patients, 16 (26%) used opioids after completing CRT and participated in the PLODE program. Before starting the program, 93 patients completed CRT between June 2017 and March 2018 and 32 (34%) used opioids at CRT completion. These patients were deemed the control group. In the PLODE group, outpatient pharmacist intervention was performed, with 29 total interventions related to opioid use, of which 16 (55%) recommended tapering or discontinuing opioids according to the definition of this program. Patients who participated in the PLODE program discontinued opioids significantly earlier than those in the control group (median time to opioid discontinuation 11 days vs. 24.5 days, p < 0.001). None of the patients in the PLODE group resumed opioid use following discontinuation or escalated opioid dosing due to worsening pain. This study showed the utility of pharmacist-initiated interventions for opioid use in patients with head and neck cancer who had completed CRT.