Clinical Opiate Withdrawal Scale Research Articles

Rapid Initiation of Injection Naltrexone for Opioid Use Disorder

Injectable extended-release (XR)-naltrexone is an effective treatment option for opioid use disorder (OUD), but the need to withdraw patients from opioid treatment prior to initiation is a barrier to implementation. To compare the effectiveness of the standard procedure (SP) with the rapid procedure (RP) for XR-naltrexone initiation. The Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone study was an optimized stepped-wedge cluster randomized trial conducted at 6 community-based inpatient addiction treatment units. Units using the SP were randomly assigned at 14-week intervals to implement the RP. Participants admitted with OUD received the procedure the unit was delivering at the time of their admission. Participant recruitment took place between March 16, 2021, and July 18, 2022. The last visit was September 21, 2022. Standard procedure, based on the XR-naltrexone package insert (approximately 5-day buprenorphine taper followed by a 7- to 10-day opioid-free period and RP, defined as 1 day of buprenorphine at minimum necessary dose, 1 opioid-free day, and ascending low doses of oral naltrexone and adjunctive medications (eg, clonidine, clonazepam, antiemetics) for opioid withdrawal. Receipt of XR-naltrexone injection prior to inpatient discharge (primary outcome). Secondary outcomes included opioid withdrawal scores and targeted safety events and serious adverse events. All analyses were intention-to-treat. A total of 415 participants with OUD were enrolled (mean [SD] age, 33.6 [8.48] years; 205 [49.4%] identified sex as male); 54 [13.0%] individuals identified as Black, 91 [21.9%] as Hispanic, 290 [69.9%] as White, and 22 [5.3%] as multiracial. Rates of successful initiation of XR-naltrexone among the RP group (141 of 225 [62.7%]) were noninferior to those of the SP group (68 of 190 [35.8%]) (odds ratio [OR], 3.60; 95% CI, 2.12-6.10). Withdrawal did not differ significantly between conditions (proportion of days with a moderate or greater maximum Clinical Opiate Withdrawal Scale score (>12) for RP vs SP: OR, 1.25; 95% CI, 0.62-2.50). Targeted safety events (RP: 12 [5.3%]; SP: 4 [2.1%]) and serious adverse events (RP: 15 [6.7%]; SP: 3 [1.6%]) were infrequent but occurred more often with RP than SP. In this trial, the RP of XR-naltrexone initiation was noninferior to the standard approach and saved time, although it required more intensive medical management and safety monitoring. The results of this trial suggest that rapid initiation could make XR-naltrexone a more viable treatment for patients with OUD. ClinicalTrials.gov Identifier: NCT04762537.

Buprenorphine induced opioid withdrawal syndrome relieved by adjunctive Magnesium: A clinical trial

IntroductionPrecipitated opioid withdrawal syndrome (OWS) is a severe and intolerable situation that may occur by a pharmaceutical agent. Reactivation of inhibited N-methyl-d-aspartate (NMDA) receptor in person with prolonged opioid use can led to severe OWS. We conducted a double-blind, randomized clinical trial to assess the effect of magnesium sulfate (MGSO4) as an NMDA receptor antagonist on OWS. Materials and methodsThe study randomly divided forty patients with precipitated OWS due to partial agonist (buprenorphine) use referred to the emergency unit of Toxicology Department of Mashhad University of Medical Sciences, Iran; into two groups. The control group received conventional therapies, including clonidine 0.1 mg tablet each hour, intravenous infusion of 10 mg diazepam every 30 min, and IV paracetamol (Acetaminophen) 1 g, while the intervention group received 3 g of MGSO4 in 20 min and then 10 mg/kg/h up to 2 h, in addition to the conventional treatment. The clinical opiate withdrawal scale (COWS) evaluated OWS at the start of the treatment, 30 min, and 2 h later. ResultsBoth groups had similar demographic, opiate types, and COWS severity at the start of the intervention. COWS was lower in the intervention than the control group at 30 min (11.20 ± 2.86 and 14.65 ± 2.36, respectively, P = 0.002) and at 2 h (3.2 ± 1.61 and 11.25 ± 3.27, respectively, P < 0.001) after treatment. The intervention group received lesser doses of clonidine (0.12 ± 0.51 and 0.17 ± 0.45 mg, P = 0.003) and Diazepam (13.50 ± 5.87, 24.0 ± 6.80 mg, P = 0.001) than the control group. Serum magnesium levels raised from 1.71 ± 0.13 mmol/L to 2.73 ± 0.13 mmol/L in the intervention group. ConclusionMagnesium can significantly reduce the severity of OWS. Additional studies are required to confirm these results.

Pharmacokinetic-pharmacodynamic analysis of drug liking blockade by buprenorphine subcutaneous depot (CAM2038) in participants with opioid use disorder

Buprenorphine is used to treat opioid use disorder (OUD). Weekly and monthly subcutaneous long-acting buprenorphine injections (CAM2038) provide more stable buprenorphine plasma levels and reduce the treatment burden, misuse, and diversion associated with sublingual transmucosal buprenorphine formulations. To characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship, a maximum inhibition (Imax) model was developed relating CAM2038 buprenorphine plasma concentration to drug liking maximum effect (Emax) visual analog scale (VAS; bipolar) score after intramuscular hydromorphone administration. Data included time-matched observations of buprenorphine plasma concentration and drug liking Emax VAS score after hydromorphone 18 mg administration in 47 non-treatment-seeking adults with moderate to severe OUD in a phase 2 study. Analysis used non-‍linear mixed-effects modeling (NONMEM®). The final Imax model adequately described the PK/PD relationship between buprenorphine plasma concentration and drug liking Emax VAS score. Simulations showed drug liking was effectively blocked at low buprenorphine plasma concentrations (0.4 ng/mL) where the upper 95% confidence interval of the drug liking Emax VAS score was below the pre-defined 11-point complete blockade threshold. The buprenorphine plasma concentration required to achieve 90% of the maximal effect (IC90) of drug liking was 0.675 ng/mL. Interindividual variability in responses to buprenorphine was observed; some participants experienced fluctuating responses, and a few did not achieve drug liking blockade even with higher buprenorphine plasma concentrations. This affirms the need to individualize treatment and titrate doses for optimal treatment outcomes. PK/PD models were also developed for desire to use VAS and Clinical Opiate Withdrawal Scale (COWS) scores, with results aligned to those for drug liking.

Open-label investigation of rapid initiation of extended-release buprenorphine in patients using fentanyl and fentanyl analogs.

Synthetic opioids, including fentanyl and fentanyl analogs, account for over 70,000 annual overdose deaths in the United States, but there is limited information examining methods of induction and maintenance outcomes for buprenorphine treatment of patients with opioid use disorder (OUD) using these opioids. A secondary analysis of results grouped by fentanyl use status was completed for an open-label study with rapid induction of extended-release buprenorphine in the inpatient research unit. Eligible participants received a single 4 mg dose of transmucosal buprenorphine (BUP-TM) followed by an extended-release buprenorphine 300 mg injection ([BUP-XR]) after approximately 1 h. An extension study continued follow-up up to 6 months (6 monthly injections). Among participants with fentanyl-positive urine samples (FEN+; n = 19), all received BUP-TM, 17 received BUP-XR, 13 elected to receive a second BUP-XR injection, and 10 received all six scheduled injections. Among participants with fentanyl-negative samples (FEN-; n = 7), all received BUP-TM and BUP-XR, four elected to receive a second injection, and two participants received all six scheduled injections. Induction day clinical opioid withdrawal scale (COWS) scores were similar for FEN+ and FEN- groups. In the FEN+ group, mean COWS scores fell to below 5 within 24 h of BUP-XR injection. The treatment of individuals with OUD using fentanyl with a rapid 1-day induction to BUP-XR 300 mg injection is feasible and well-tolerated. A prospective trial of participants grouped by fentanyl use status at induction demonstrates comparable patient retention and clinical response following single-day induction of BUP-XR in participants who are FEN+ and FEN-.

Impact of Universal Screening and Automated Clinical Decision Support for the Treatment of Opioid Use Disorder in Emergency Departments: A Difference-in-Differences Analysis.

Emergency department (ED)-initiated buprenorphine improves outcomes in patients with opioid use disorder; however, adoption varies widely. To reduce variability, we implemented a nurse-driven triage screening question in the electronic health record to identify patients with opioid use disorder, followed by targeted electronic health record prompts to measure withdrawal and guide next steps in management, including initiation of treatment. Our objective was to assess the impact of screening implementation in 3 urban, academic EDs. We conducted a quasiexperimental study of opioid use disorder-related ED visits using electronic health record data from January 2020 to June 2022. The triage protocol was implemented in 3 EDs between March and July 2021, and 2 other EDs in the health system served as controls. We evaluated changes in treatment measures over time and used a difference-in-differences analysis to compare outcomes in the 3 intervention EDs with those in the 2 controls. There were 2,462 visits in the intervention hospitals (1,258 in the preperiod and 1,204 in the postperiod) and 731 in the control hospitals (459 in the preperiod and 272 in the postperiod). Patient characteristics within the intervention and control EDs were similar across the time periods. Compared with the control hospitals, the triage protocol was associated with a 17% greater increase in withdrawal assessment, using the Clinical Opioid Withdrawal Scale (COWS) (95% CI 7 to 27). Buprenorphine prescriptions at discharge also increased by 5% (95% CI 0% to 10%), and naloxone prescriptions increased by 12% points (95% CI 1% to 22%) in the intervention EDs relative to controls. An ED triage screening and treatment protocol led to increased assessment and treatment of opioid use disorder. Protocols designed to make screening and treatment the default practice have promise in increasing the implementation of evidence-based treatment ED opioid use disorder care.

Trazodone for sleep disturbance in opioid dependent patients maintained on buprenorphine: A double blind, placebo-controlled trial

BackgroundSleep disturbances are seen even in individuals on opioid agonist treatment (OAT). Established pharmacotherapy for sleep disturbances such as benzodiazepines have misuse potential and increased mortality risk in patients with OAT. No study has explored the role of trazodone on sleep disturbance in individuals maintained on buprenorphine. We aimed to assess the efficacy of trazodone in improving sleep disturbance among individuals maintained on buprenorphine. MethodsThe study was a double-blind, placebo-controlled, parallel, randomised trial. Adult males (18–60 years) stabilised on buprenorphine with Pittsburgh Sleep Quality Index (PSQI) score of above five, without other psychiatric comorbidity were randomised to receive either trazodone (50–150mg per day) or placebo. Sleep-50 questionnaire, Epworth Sleepiness Scale (ESS), Brief Pain Inventory (BPI), Clinical Opiate Withdrawal Scale (COWS), Depression, Anxiety and Stress Scale (DASS)−21, Visual Analogue Scale (VAS) for opioid craving, and PSQI were assessed at baseline and at the end of six weeks. ResultsFifty-one patients were allocated to trazodone arm and 49 to placebo arm. Side-effects of trazodone were minimal and well-tolerated with comparable discontiuation rates between both groups. Significantly greater proportion of patients on trazodone (82%, mean dose 101.9 mg) had PSQI scores five or less than those on placebo (16%) at the end of six weeks. Sleep improvement was in various components like sleep quality, latency, efficiency, and duration of sleep. ConclusionTrazodone is well-tolerated and effective in improving sleep disturbances in individuals with opioid dependence maintained on buprenorphine over a six-week period.

Low dose IV buprenorphine inductions for patients with opioid use disorder and concurrent pain: a retrospective case series

BackgroundHospitalizations are a vital opportunity for the initiation of life-saving opioid agonist therapy (OAT) for patients with opioid use disorder. A novel approach to OAT initiation is the use of IV buprenorphine for low dose induction, which allows patients to immediately start buprenorphine at any point in a hospitalization without stopping full agonist opioids or experiencing significant withdrawal.MethodsThis is a retrospective case series of 33 patients with opioid use disorder concurrently treated with full agonist opioids for pain who voluntarily underwent low dose induction at a tertiary academic medical center. Low dose induction is the process of initiating very low doses of buprenorphine at fixed intervals with gradual dose increases in patients who recently received or are simultaneously treated with full opioid agonists. Our study reports one primary outcome: successful completion of the low dose induction (i.e. transitioned from low dose IV buprenorphine to sublingual buprenorphine-naloxone) and three secondary outcomes: discharge from the hospital with buprenorphine-naloxone prescription, self-reported pain scores, and nursing-assessed clinical opiate withdrawal scale (COWS) scores over a 6-day period, using descriptive statistics. COWS and pain scores were obtained from day 0 (prior to starting the low dose induction) to day 5 to assess the effect on withdrawal symptoms and pain control.ResultsThirty patients completed the low dose induction (30/33, 90.9%). Thirty patients (30/33, 90.9%) were discharged with a buprenorphine prescription. Pain and COWS scores remained stable over the course of the study period. Mean COWS scores for all patients were 2.6 (SD 2.8) on day 0 and 1.6 (SD 2.6) on day 5. Mean pain scores for all patients were 4.4 (SD 2.1) on day 0 and 3.5 on day 5 (SD 2.1).ConclusionsThis study found that an IV buprenorphine low dose induction protocol was well-tolerated by a group of 33 hospitalized patients with opioid use disorder with co-occurring pain requiring full agonist opioid therapy. COWS and pain scores improved for the majority of patients. This is the first case series to report mean daily COWS and pain scores over an extended period throughout a low dose induction process.

Assessment of the physical dependence potential of difelikefalin: randomized placebo-controlled study in patients receiving hemodialysis.

Difelikefalin is a selective kappa opioid receptor agonist approved for treating moderate-to-severe pruritus in adults undergoing hemodialysis (HD). Difelikefalin is not a controlled substance under the Controlled Substances Act. This study assessed the potential for developing physical dependence on difelikefalin in patients undergoing HD. Eligible patients received open-label difelikefalin after each dialysis session for 3 weeks before entering a 2-week double-blind phase, when they were randomized to either continue difelikefalin or to switch to receiving placebo. Signs of physical withdrawal were assessed using the Clinical Opiate Withdrawal Scale (COWS), several patient-reported scales, and physiological measures. The primary endpoint was the between-group difference in mean maximum COWS total scores during the double-blind phase; the mean difference (placebo - difelikefalin) was compared against a pre-defined noninferiority limit (+4). Thirty-five patients (57.1% male; 91.4% Black or African American; median [range] age 58 [28-77] years) were included, of which 30 were randomized (placebo, n=14; difelikefalin, n=16). The least square mean difference in maximum COWS total scores was 0.52 (95% confidence interval [CI]: -0.56, 1.59). The upper CI limit (1.59) was below +4, indicating that patients who discontinued difelikefalin (placebo group) had similar withdrawal scores to patients who continued difelikefalin. Additional assessments supported the COWS results, showing no meaningful differences between groups in physiological measures or in patient-reported measures of sleep or physical withdrawal. These results demonstrate that abruptly discontinuing chronic difelikefalin treatment in patients undergoing HD does not produce signs or symptoms of physical withdrawal.

Prevalence and Risk Factors for Iatrogenic Opioid Withdrawal in Medical Critical Care Patients.

To identify the and risk factors for IWS in adult patients admitted to critical care medicine services who received greater than or equal to 24 hours of continuous opioid infusion therapy. A prospective, observational study was conducted in a tertiary care hospital in adult medical ICU patients. Ninety-two patients who received greater than or equal to 24 hours of continuous opioid infusions were included in the study. Patients were assessed daily after opioid infusion discontinuation using the Clinical Opiate Withdrawal Scale (COWS) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) opioid withdrawal criteria for a maximum of 5 days. The primary outcome was the prevalence of IWS of moderate severity or greater using COWS. Secondary outcomes included the prevalence of IWS diagnosis of any severity based on COWS, the prevalence of IWS diagnosis based on a positive DSM-V score, and the identification of potential risk factors for developing IWS of any severity. Four hundred forty-seven patients received greater than or equal to 24 hours of continuous opioid therapy. Of these, 385 were excluded, leaving 92 patients included in the final analysis. Except for a higher prevalence of psychiatric history in the IWS-positive group, baseline characteristics were similar. Overall, 11 patients (12%) developed IWS of moderate severity or greater, based on COWS. The IWS-positive group also had longer durations of opioid infusions, higher cumulative opioid infusion doses, higher mean daily doses, and higher infusion rates at any given time. The concomitant use of dexmedetomidine (38.3 vs 15.6%, p = 0.014) and benzodiazepines (63.8 vs 37.8%, p = 0.021) during or after the opioid infusion were significantly higher in the IWS-positive group compared with the IWS-negative group. No significant differences were found between the two groups for scheduled or as needed opioids after cessation of the opioid infusion. Continuous opioid infusions greater than or equal to 72 hours and total daily dose greater than or equal to 1,200 μg were found to be independent predictors for the development of iatrogenic opioid withdrawal via logistic regression. Approximately one in every eight patients receiving continuous infusion opioid for greater than 24 hours while mechanically ventilated in the medical ICU will develop IWS of moderate severity or greater; this increases to one in three patients diagnosed with DSM-V criteria or any level of IWS severity. Patients receiving opioid infusions greater than or equal to 72 hours, or a total daily fentanyl dose of greater than or equal to 1,200 μg (~ 50 μg/hr) are at a higher risk for developing IWS and should be monitored as part of clinical practice when opioid infusions are discontinued.

Operational definition of precipitated opioid withdrawal.

Opioid withdrawal can be expressed as both a spontaneous and precipitated syndrome. Although spontaneous withdrawal is well-characterized, there is no operational definition of precipitated opioid withdrawal. People (N = 106) with opioid use disorder maintained on morphine received 0.4 mg intramuscular naloxone and completed self-report (Subjective Opiate Withdrawal Scale, SOWS), visual analog scale (VAS), Bad Effects and Sick, and observer ratings (Clinical Opiate Withdrawal Scale, COWS). Time to peak severity and minimal clinically important difference (MCID) in withdrawal severity were calculated. Principal component analysis (PCA) during peak severity were conducted and analyzed with repeated measures analyses of variance (ANOVA). Within 60 min, 89% of people reported peak SOWS ratings and 90% of people had peak COWS scores as made by raters. Self-reported signs of eyes tearing, yawning, nose running, perspiring, hot flashes, and observed changes in pupil diameter and rhinorrhea/lacrimation were uniquely associated with precipitated withdrawal. VAS ratings of Bad Effect and Sick served as statistically significant severity categories (0, 1-40, 41-80, and 81-100) for MCID evaluations and revealed participants' identification with an increase of 10 [SOWS; 15% maximum percent effect (MPE)] and 6 (COWS; 12% MPE) points as meaningful shifts in withdrawal severity indicative of precipitated withdrawal. Data suggested that a change of 10 (15% MPE) and 6 (12% MPE) points on the SOWS and COWS, respectively, that occurred within 60 min of antagonist administration was identified by participants as a clinically meaningful increase in symptom severity. These data provide a method to begin examining precipitated opioid withdrawal.

Prospective Study of Masimo NSS-2 BRIDGE; as a Non-Pharmacological Treatment for Acute Opioid Withdrawal Symptoms

PurposeOpioids are commonly employed for treatment of acute and chronic pain. However, continued opioid use can lead to opioid use disorder. Opioid withdrawal symptoms can be severe, and avoidance of the discomfort is a key barrier to voluntary discontinuation. The NSS-2 BRIDGE™ (Masimo Corporation, Irvine, CA) is a percutaneous nerve field stimulator that can decrease symptoms of acute opiate withdrawal. The device fits behind the ear and stimulates branches of Cranial Nerves V, VII, IX, X, and periauricular occipital nerves, which synapse with nuclei involved in processing perception of pain and pleasure, as well as in addiction. The objective of this prospective study was to investigate the effects of NSS-2 BRIDGE™ on outpatients experiencing acute opioid withdrawal symptoms. We hypothesized that participants using the active NSS-2-BRIDGE™ device would have a reduction in Clinical Opioid Withdrawal Scale (COWS) scores compared to those using the sham device, when monitored at 30-minute intervals. MethodsAdult patients (≥18 years old) who voluntarily presented to the Zephyr outpatient clinic (Santa Anna, CA) were enrolled in the study and fitted with the NSS-2 BRIDGE™ device. Initial COWS scores were recorded at baseline and at 30 minutes intervals, up to 120 minutes. ResultsThe study included 16 participants, 8 subjects in each group. The mean COWS score of the active group decreased from 17.125 at baseline to 5.75 at 30 minutes, a mean decrease of 11.375 (P<0.001). The mean COWS score of the sham group decreased from 16.25 at baseline to 12.875 at 30 minutes, a mean decrease of 3.375 (P=0.186). ConclusionThe active device group showed a statistically and clinically significant mean drop in COWS score compared to the sham group. This study demonstrated that NSS-2 BRIDGE™ can assist in opioid withdrawal and may increase initial treatment retention.

Differential effect of cannabis use on opioid agonist treatment outcomes: Exploratory analyses from the OPTIMA study

IntroductionConflictual evidence exists regarding the effects of cannabis use on the outcomes of opioid agonist therapy (OAT). In this exploratory analysis, we examined the effect of recent cannabis use on opioid use, craving, and withdrawal symptoms, in individuals participating in a trial comparing flexible buprenorphine/naloxone (BUP/NX) take-home dosing model to witnessed ingestion of methadone. MethodsWe analyzed data from a multi-centric, pragmatic, 24-week, open label, randomized controlled trial in individuals with prescription-type opioid use disorder (n = 272), randomly assigned to BUP/NX (n = 138) or methadone (n = 134). The study measured last week cannabis and opioid use via timeline-follow back, recorded at baseline and every two weeks during the study. Craving symptoms were measured using the Brief Substance Craving Scale at baseline, and weeks 2, 6, 10, 14, 18 and 22. The study measured opioid withdrawal symptoms via Clinical Opiate Withdrawal Scale at treatment initiation and weeks 2, 4, and 6. ResultsThe mean maximum dose taken during the study was 17.3 mg/day (range = 0.5–32 mg/day) for BUP/NX group and 67.7 mg/day (range = 10–170 mg/day) in the methadone group. Repeated measures generalized linear mixed models demonstrated that cannabis use in the last week (mean of 2.3 days) was not significantly associated with last week opioid use (aβ ± standard error (SE) = −0.06 ± 0.04; p = 0.15), craving (aβ ± SE = −0.05 ± 0.08, p = 0.49), or withdrawal symptoms (aβ ± SE = 0.09 ± 0.1, p = 0.36). Bayes factor (BF) for each of the tested models supported the null hypothesis (BF < 0.3). ConclusionsThe current study did not demonstrate a statistically significant effect of cannabis use on outcomes of interest in the context of a pragmatic randomized-controlled trial. These findings replicated previous results reporting no effect of cannabis use on opioid-related outcomes.

Inpatient Buprenorphine Induction for Opioid Use Disorder in Pregnancy.

Objective Buprenorphine is a commonly used medication to manage opioid use disorder, however there is limited data to guide induction protocols specifically during pregnancy.Similar to non-pregnant patients theClinical Opiate Withdrawal Scale (COWS) is often used to guide induction and titration of buprenorphine in pregnancy.The objective of this retrospective descriptive study is to assess the inpatient buprenorphine induction patterns, treatment retention, and pregnancy outcomes among obstetric patients with opioid use disorder seeking treatment. Study design This was a retrospective study of obstetric patients with opioid use disorder admitted for inpatient buprenorphine induction at a large academic center between May 2015 to 2020. A descriptive analysis of the cohort, induction patterns, and dose retention after discharge were evaluated in addition to obstetric and neonatal outcomes. Results Sixty patients were admitted for inpatient buprenorphine induction at a median gestational age of 16.7 weeks. The median COWS score on presentation was 9. The starting dose for half of the patients (30 out of 60 patients) was 8 mg of buprenorphine, while 24 patients were started at 4 mg. The median duration of hospitalization was three days (range 2-12). The median buprenorphine dose upon discharge was 10 mg (range 4-20). Only 13 of the 35 patients (37%) who desired prenatal care at our institution returned to receive routine prenatal care. Of the 12 (20%) patients who delivered at our institution, nine were live births (75%). Among the live births, the median gestational age at delivery was 37.4 weeks, birth weight 3085 grams, and only one (8%) developed neonatal abstinence syndrome. Conclusion When usingthe Clinical Opiate Withdrawal Scale to guide inpatient buprenorphine titration for pregnant patients with opioid use disorder it takes approximately three days to establish a satisfactory maintenance dose with the median dose at discharge in this population being 10 mg. The majority of patients who followed up after hospital discharge did not need dose adjustments.

Association of Urine Fentanyl Concentration With Severity of Opioid Withdrawal Among Patients Presenting to the Emergency Department.

Fentanyl is involved in most US drug overdose deaths and its use can complicate opioid withdrawal management. Clinical applications of quantitative urine fentanyl testing have not been demonstrated previously. The aim of this study was to determine whether urine fentanyl concentration is associated with severity of opioid withdrawal. This is a retrospective cross-sectional study. This study was conducted in 3 emergency departments in an urban, academic health system from January 1, 2020, to December 31, 2021. This study included patients with opioid use disorder, detectable urine fentanyl or norfentanyl, and Clinical Opiate Withdrawal Scale (COWS) recorded within 6 hours of urine drug testing. The primary exposure was urine fentanyl concentration stratified as high (>400 ng/mL), medium (40-399 ng/mL), or low (<40 ng/mL). The primary outcome was opioid withdrawal severity measured with COWS within 6 hours before or after urine specimen collection. We used a generalized linear model with γ distribution and log-link function to estimate the adjusted association between COWS and the exposures. For the 1127 patients in our sample, the mean age (SD) was 40.0 (10.7), 384 (34.1%) identified as female, 332 (29.5%) reported their race/ethnicity as non-Hispanic Black, and 658 (58.4%) reported their race/ethnicity as non-Hispanic White. For patients with high urine fentanyl concentrations, the adjusted mean COWS (95% confidence interval) was 4.4 (3.9-4.8) compared with 5.5 (5.1-6.0) among those with medium and 7.7 (6.8-8.7) among those with low fentanyl concentrations. Lower urine fentanyl concentration was associated with more severe opioid withdrawal, suggesting potential clinical applications for quantitative urine measurements in evolving approaches to fentanyl withdrawal management.

Low-dose Initiation of Buprenorphine in Hospitalized Patients Using Buccal Buprenorphine: A Case Series.

To describe a low-dose buprenorphine initiation strategy with buccal buprenorphine. This is a case series of hospitalized patients with opioid use disorder (OUD) and/or chronic pain who underwent low-dose buprenorphine initiation with buccal buprenorphine to sublingual buprenorphine. Results are descriptively reported. Forty-five patients underwent low-dose buprenorphine initiation from January 2020 to July 2021. Twenty-two (49%) patients had OUD only, 5 (11%) patients had chronic pain only, and 18 (40%) patients had both OUD and chronic pain. Thirty-six (80%) patients had documented history of heroin or non-prescribed fentanyl use before admission. Acute pain in 34 (76%) patients was the most commonly documented rationale for low-dose buprenorphine initiation. Methadone was the most common outpatient opioid utilized before admission (53%). The addiction medicine service consulted on 44 (98%) cases and median length of stay was approximately 2 weeks. Thirty-six (80%) patients completed the transition to sublingual buprenorphine with a median completion dose of 16 mg daily. Of the 24 patients (53%) with consistently documented Clinical Opiate Withdrawal Scale scores, no patients experienced severe opioid withdrawal. Fifteen (62.5%) experienced mild or moderate withdrawal and 9 (37.5%) experienced no withdrawal (Clinical Opiate Withdrawal Scale score <5) during the entire process. Continuity of postdischarge prescription refills ranged from 0 to 37 weeks and the median number of buprenorphine refills was 7 weeks. Low-dose buprenorphine initiation with buccal buprenorphine to sublingual buprenorphine was well tolerated and can be safely and effectively utilized for patients whose clinical scenario precludes traditional buprenorphine initiation strategies.

A randomized controlled trial on the seeds of Sophora alopecuroides var. alopecuroides for the treatment of acute heroin withdrawal syndrome

Backgroundand purpose: The seeds of Sophora alopecuroides var. alopecuroides have attenuated the acute opium withdrawal syndrome in humans. Therefore, the efficacy and safety of a standardized extract of the plant for the treatment of acute heroin withdrawal syndrome was evaluated in abstinent heroin addicts. Materials and methodsThe patients were randomized to take three 400 mg extract capsules (N = 50) or placebo (N = 50) once per day orally for eight days. The severity of withdrawal syndrome was assessed by the clinical opiate withdrawal scale (COWS) as the primary outcome measure at the baseline and on the days 3 and 8. The hepatic and renal functions and complete blood count were the secondary outcome measures tested at the baseline and end of the study. ResultsThe COWS score decreased in both groups after eight days, but the decrease was significantly higher in the experimental group (p < 0.001); the effect size of the decrease was 2.64. The groups had significant differences in the COWS scores on the days 3 and 8 (p < 0.001 for both). The extract had no significant effect on the other parameters. No side effect was noted. ConclusionThe extract seems to alleviate acute heroin withdrawal syndrome safely.

Precipitated Opioid Withdrawal Treated With Ketamine in a Hospitalized Patient: A Case Report.

Although initiating buprenorphine in the presence of full opioid agonists has always been a clinical dilemma, the transition to primarily fentanyl in the drug supply has increased the urgency to find appropriate treatments for precipitated opioid withdrawal (POW). Although rare, lack of evidence on how to best treat POW threatens clinician and patient comfort in initiating life-saving medication for opioid use disorder. Ketamine has been used in emergency department settings to treat POW; this is the first case report of ketamine use in a hospitalized patient. A 38-year-old male patient with severe opioid use disorder presented to the emergency department with suicidality and opioid withdrawal 24 hours after last fentanyl use. In the first 24 hours of admission, he received sublingual buprenorphine-naloxone (BNX) 16-4 mg, resulting in Clinical Opiate Withdrawal Scale score increasing from 13 to over 36. The patient was admitted, and addiction medicine was consulted. The patient was diagnosed with POW, started on ketamine infusion, and given additional BNX 8-2 mg. Twelve hours after the ketamine infusion, the patient's Clinical Opiate Withdrawal Scale score improved to 18 but remained elevated. He received a second ketamine infusion plus additional BNX with complete resolution of symptoms within 8 hours, and he was stabilized and discharged on BNX 24-6 mg daily. Ketamine is a promising treatment for POW due to its potentiation of μ-opioid receptor-mediated signaling. This is the first case to describe POW in the inpatient hospital setting. More research is needed to establish the effectiveness and feasibility of ketamine as treatment for POW.

Opioids and restless legs syndrome: a double-edged sword.

Opioids and restless legs syndrome: a double-edged sword.

Impact of Administering Buprenorphine to Overdose Survivors Using Emergency Medical Services.

To evaluate the efficacy and safety of utilizing emergency medical services units to administer high dose buprenorphine after an overdose to treat withdrawal symptoms, reduce repeat overdose, and provide a next-day substances use disorder clinic appointment to initiate long-term treatment. This was a retrospective matched cohort study of patients who experienced an overdose and either received emergency medical services care from a buprenorphine-equipped ambulance or a nonbuprenorphine-equipped ambulance in Camden, New Jersey, an urban community with high overdose rates. There were 117 cases and 123 control patients in the final sample. Compared with a nonbuprenorphine-equipped ambulance, exposure to a buprenorphine-equipped ambulance was associated with greater odds of engaging in opioid use disorder treatment within 30 days of an emergency medical services encounter (unadjusted odds ratio: 5.62, 95% confidence interval, 2.36 to 13.39). Buprenorphine-equipped ambulance engagement did not decrease repeat overdose compared to the comparison group. Patients who received buprenorphine experienced a decrease in withdrawal symptoms. Their clinical opiate withdrawal scale score decreased from an average of 9.27 to 3.16. buprenorphine-equipped ambulances increased on-scene time by 6.12 minutes. Patients who encountered paramedics trained to administer buprenorphine and able to arrange prompt substance use disorder treatment after an acute opioid overdose demonstrated a decrease in opioid withdrawal symptoms, an increase in outpatient addiction follow-up care, and showed no difference in repeat overdose. Patients receiving buprenorphine in the out-of-hospital setting did not experience precipitated withdrawal. Expanded out-of-hospital treatment of opiate use disorder is a promising model for rapid access to buprenorphine after an overdose in a patient population that often has limited contact with the health care system.

Precipitated opioid withdrawal after buprenorphine administration in patients presenting to the emergency department: A case series.

Buprenorphine is a highly effective medication for the treatment of opioid use disorder, but it can cause precipitated withdrawal (PW) from opioids. Incidence, risk factors, and best approaches to management of PW are not well understood. Our objective was to describe adverse outcomes after buprenorphine administration among emergency department (ED) patients and assess whether they met the criteria for PW. This study is a case series using retrospective chart review in a convenience sample of patients from 3 hospitals in an urban academic health system. This study included patients who were reported by clinicians as potential cases of PW. Relevant clinical data were abstracted from the electronic health record using a structured retrospective chart review instrument. A total of 13 cases were included and classified into the following 3 categories: (1) PW after buprenorphine administration consistent with guidelines (n=5), (2) PW after deviating from guidelines (n=4), and (3) protracted opioid withdrawal with no increase in Clinical Opiate Withdrawal Scale score (n=4). A total of 11 patients had urine drug testing positive for fentanyl, and 11 patients received additional doses of buprenorphine for symptom management. Of the patients, 5 had self-directed hospital discharges, and 6 were ultimately discharged with prescriptions for buprenorphine. Cases of adverse outcomes after buprenorphine administration in the ED and hospital meet criteria for PW, although some cases may have represented protracted opioid withdrawal. Further investigation into the incidence, risk factors, management of PW as well as patient perspectives is needed to expand and sustain the use of buprenorphine in EDs and hospitals.