Clinical Opiate Withdrawal Scale Score Research Articles

Extended-Release 7-Day Injectable Buprenorphine for Patients With Minimal to Mild Opioid Withdrawal.

Buprenorphine is an effective yet underused treatment for opioid use disorder (OUD). To evaluate the feasibility (acceptability, tolerability, and safety) of 7-day injectable extended-release buprenorphine in patients with minimal to mild opioid withdrawal. This nonrandomized trial comprising 4 emergency departments in the Northeast, mid-Atlantic, and Pacific geographic areas of the US included adults aged 18 years or older with moderate to severe OUD and Clinical Opiate Withdrawal Scale (COWS) scores less than 8 (minimal to mild), in which scores range from 0 to 7, with higher scores indicating increasing withdrawal. Exclusion criteria included methadone-positive urine, pregnancy, overdose, or required admission. Outcomes were assessed at baseline, daily for 7 days by telephone surveys, and in person at 7 days. Patient recruitment occurred between July 13, 2020, and May 25, 2023. Injection of a 24-mg dose of a weekly extended-release formulation of buprenorphine (CAM2038) and referral for ongoing OUD care. Primary feasibility outcomes included the number of patients who (1) experienced a 5-point or greater increase in the COWS score or (2) transitioned to moderate or greater withdrawal (COWS score ≥13) within 4 hours of extended-release buprenorphine or (3) experienced precipitated withdrawal within 1 hour of extended-release buprenorphine. Secondary outcomes included injection pain, satisfaction, craving, use of nonprescribed opioids, adverse events, and engagement in OUD treatment. A total of 100 adult patients were enrolled (mean [SD] age, 36.5 [8.7] years; 72% male). Among the patients, 10 (10.0% [95% CI, 4.9%-17.6%]) experienced a 5-point or greater increase in COWS and 7 (7.0% [95% CI, 2.9%-13.9%]) transitioned to moderate or greater withdrawal within 4 hours, and 2 (2.0% [95% CI, 0.2%-7.0%]) experienced precipitated withdrawal within 1 hour of extended-release buprenorphine. A total of 7 patients (7.0% [95% CI, 2.9%-13.9%]) experienced precipitated withdrawal within 4 hours of extended-release buprenorphine, which included 2 of 63 (3.2%) with a COWS score of 4 to 7 and 5 of 37 (13.5%) with a COWS score of 0 to 3. Site pain scores (based on a total pain score of 10, in which 0 indicated no pain and 10 was the worst possible pain) after injection were low immediately (median, 2.0; range, 0-10.0) and after 4 hours (median, 0; range, 0-10.0). On any given day among those who responded, between 29 (33%) and 31 (43%) patients reported no cravings and between 59 (78%) and 75 (85%) reported no use of opioids; 57 patients (60%) reported no days of opioid use. Improving privacy (62%) and not requiring daily medication (67%) were deemed extremely important. Seventy-three patients (73%) were engaged in OUD treatment on day 7. Five serious adverse events occurred that required hospitalization, of which 2 were associated with medication. This nonrandomized trial of the feasibility of a 7-day buprenorphine injectable in patients with minimal to mild opioid withdrawal (COWS scores, 0-7) found the formulation to be acceptable, well tolerated, and safe in those with COWS scores of 4 to 7. This new medication formulation could substantially increase the number of patients with OUD receiving buprenorphine. ClinicalTrials.gov Identifier: NCT04225598.

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.

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.

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.

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.

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.

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.

Repeated measures analysis of opioid use disorder treatment on clinical opiate withdrawal scale in a randomized clinical trial: sex differences

Purpose Sex differences may exist in opioid use disorder (OUD) treatment. This study examined the treatment effects of buprenorphine/naloxone (BUP/NX) and methadone (MET) on the Clinical Opiate Withdrawal Scale (COWS) score in individuals with OUD and tested whether the associations differ by sex. Method We performed a secondary analysis of the data from the National Drug Abuse Treatment Clinical Trials Network (CTN) protocol-0027. A total of 1269 participants (861 males and 408 females) being aged 18 or older with OUD were randomly assigned to receive BUP/NX (n = 740) or MET (n = 529). The paired t test was initially used to compare the COWS scores between pre-dose and post-dose for BUP/NX and MET treatments, separately. The linear mixed model was used to examine the changes in COWS score adjusted for baseline demographic, substance use, and mental health disorders. The interaction of sex and treatment was detected and stratified analysis by sex was conducted. Results The paired t test showed that both BUP/NX and MET treatments significantly reduced the COWS scores (p values <0.0001). BUP/NX revealed higher COWS scores than MET (p = 0.0008) and females demonstrated significantly higher COWS scores than males (p = 0.0169). Stratified by sex, BUP/NX compared with MET revealed higher COWS scores only in males (p = 0.0043), whereas baseline amphetamines use disorder and major depressive disorder were significantly associated with COWS scores in females (p = 0.0158 and 0.0422, respectively). Conclusions Both BUP/NX and MET are effective in decreasing opioid withdrawal symptoms via COWS scores, however, treatment plans for OUD by clinical providers should consider sex differences.

Transitioning From High-dose Methadone to Buprenorphine Using a Microdosing Approach: Unique Considerations at ASAM Level 3 Facilities.

Transitions from high-dose methadone to buprenorphine for treatment of opioid use disorder (OUD) present risk of precipitated withdrawal related to the introduction of a high-affinity partial agonist at the mu-opioid receptor after occupancy by a lower-affinity full agonist. Various strategies have been explored to maintain patient stability during this process, including microdosing buprenorphine. Current literature lacks consensus on an optimal setting and strategy for initiating a buprenorphine microdosing protocol and gives little detail on patients' conditions after the acute transition period. We report a 6-day microdosing transition from methadone 100 mg directly to sublingual buprenorphine, followed by a 20-day period of monitoring and additional treatment. This patient tolerated a sublingual buprenorphine microdosing protocol while using supportive medications with a peak Clinical Opiate Withdrawal Scale score of 6. The patient's most significant withdrawal symptoms occurred several days after completion of the microdosing process. This case demonstrates the feasibility of using a transmucosal buprenorphine formulation in microdosing transitions from high-dose methadone directly to buprenorphine, and highlights the utility of a medically monitored intensive inpatient setting (American Society of Addiction Medicine level 3.7) in providing appropriate monitoring and treatment during and after a microdosing transition.

Delivering transcutaneous auricular neurostimulation (tAN) to improve symptoms associated with opioid withdrawal: results from a prospective clinical trial

BackgroundAs pharmacological treatments are the primary option for opioid use disorder, neuromodulation has recently demonstrated efficacy in managing opioid withdrawal syndrome (OWS). This study investigated the safety and effectiveness of transcutaneous auricular neurostimulation (tAN) for managing OWS.MethodsThis prospective inpatient trial included a 30-minute randomized, sham-controlled, double-blind period followed by a 5-day open-label period. Adults with physical dependence on opioids were randomized to receive active or sham tAN following abrupt opioid discontinuation. The Clinical Opiate Withdrawal Scale (COWS) was used to determine withdrawal level, and participants were required to have a baseline COWS score ≥ 13 before enrollment. The double-blind period of the study occurred during the first 30-minutes to assess the acute effects of tAN therapy compared to a sham control. Group 1 received active tAN during both the 30-minute double-blind period and the 5-day open-label period. Group 2 received passive sham tAN (no stimulation) during the double-blind period, followed by active tAN during the 5-day open-label period. The primary outcome was change in COWS from baseline to 60-minutes of active tAN (pooled across groups, accounting for 30-minute delay). Secondary outcomes included difference in change in COWS scores between groups after 30-minutes of active or sham tAN, change in COWS scores after 120-minutes of active tAN, and change in COWS scores on Days 2–5. Non-opioid comfort medications were administered during the trial.ResultsAcross all thirty-one participants, the mean (SD) COWS scores relative to baseline were reduced by 7.0 (4.7) points after 60-minutes of active tAN across both groups (p < 0.0001; Cohen’s d = 2.0), demonstrating a significant and clinically meaningful reduction of 45.9%. After 30-minutes of active tAN (Group 1) or sham tAN (Group 2), the active tAN group demonstrated a significantly greater COWS score reduction than the sham tAN group (41.7% vs. 24.1%; p = 0.036). Participants across both groups achieved an average COWS reduction up to 74.7% on Days 2–5.ConclusionResults demonstrate tAN is a safe and effective non-opioid approach for reducing symptoms of OWS. This study supported an FDA clearance.Clinical trial registrationclinicaltrials.gov/ct2/show/NCT04075214, Identifier: NCT04075214, Release Date: August 28, 2019.

Association of PDYN 68-bp VNTR polymorphism with sublingual buprenorphine/naloxone treatment and with opioid or alcohol use disorder: Effect on craving, depression, anxiety and age onset of first use

In this case-control study (423 Turkish subjects), the functional pro-dynorphin (PDYN) 68-bp VNTR polymorphism was genotyped in opioid users receiving sublingual buprenorphine/naloxone treatment (SBNT; n = 129, 119 males and 10 females), in opioid users (OUD; n = 99, 90 males and 9 females), in alcohol users (AUD; n = 75, 75 males) and in controls (n = 120, 109 males and 11 females) to determine the effect of this polymorphism on different treatment responses, heroin or alcohol dependence as well as age onset of first use. The PDYN 68-bp alleles were determined based on the number of repeats and genotypes were classified as “short/short (SS)”, “short-long (SL)” and “long-long (LL)”. The intensity of craving, withdrawal, depression and anxiety were measured by the Substance Craving Scale (SCS), the Clinical Opiate Withdrawal Scale (COWS), the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI), respectively. Healthy controls (5.5 ± 5.8) had significantly lower levels of depressive symptoms compared to OUD (25.4 ± 13.5), AUD (22.5 ± 11.3) and SBNT (19.29 ± 12.2) groups. In OUD group, the LL genotype was associated with decreased intensity of anxiety and depressive symptoms than the SS+SL genotype. The BDI-II scores for PDYN VNTR genotypes within the 4 groups were analysed by two-way ANOVA and statistical differences were found for the groups. SBNT group had significantly lower COWS score than OUD group (1.00 versus 3.00). There were statistically significant differences in the median BAI (11 versus 24) and BDI-II scores (17.5 versus 25) between OUD and SBNT groups, supporting the antidepressant and anxiolytic effects of SBNT in persons with OUD.

Management of smack addiction through adjuvant Ayurvedic treatment

The smack addiction is very much spreading nowadays among the youth, which is injurious for a healthy society. Opiates are highly addictive. Long-term use of opiates causes dependence, leading to tolerance. Overdose incidents occur due to chronic intake or addiction that can lead to life-threatening complications. In the present case, a 21-year-old male with a history of smack addiction for the last three years presented to the outpatient department with withdrawal symptoms including tremors, running nose, watering eyes, body ache, sleeplessness, sweating, nausea, irritability, and diarrhea. The assessment of withdrawal symptoms was based on Clinical Opiate Withdrawal Scale (COWS). The multimodal treatment including Shirodhara (~oil dripping on the forehead) with Ashwagandha taila and Tila taila, Sarvanga abhyanga (~synchronized whole body massage with medicated oil) with Dashmoola taila, Svedana (~sudation) using Dashmoola kwatha, and Nasya (~medications through nasal route) with Jatamansi taila along with internal medications of Vishatinduka vati and Sameeragaja kesari rasa showed promising results. Within one month of the treatment, the withdrawal symptoms of smack addiction were reduced considerably. The COWS score decreased to 3 from 22 after three weeks of treatment, inferring that multimodal Ayurvedic treatment can be an effective and safe solution in case of smack addictions.

Emergency department-initiated buprenorphine protocols: A national evaluation.

ObjectiveEmergency department‐initiated buprenorphine (BUP) for opioid use disorder is an evidence‐based practice, but limited data exist on BUP initiation practices in real‐world settings. We sought to characterize protocols for BUP initiation among a geographically diverse sample of emergency departments (EDs).MethodsIn December 2020, we reviewed prestudy clinical BUP initiation protocols from all EDs participating in CTN0099 Emergency Department‐INitiated bupreNOrphine VAlidaTION (ED‐INNOVATION). We abstracted information on processes for identification of treatment‐eligible patients, BUP administration, and discharge care.ResultsAll participating ED‐INNOVATION sites across 22 states submitted protocols; 31 protocols were analyzed. Identification of treatment‐eligible patients: Most EDs 22 (71%) relied on clinician judgment to determine appropriateness of BUP treatment with only 7 (23%) requiring decision support tools or diagnosis checklists. Before BUP initiation, 27 (87%) protocols required a documented Clinical Opiate Withdrawal Scale (COWS) score; 4 (13%) required a clinical diagnosis of withdrawal with optional COWS score. Twenty‐seven (87%) recommended a minimum COWS score of 8 for ED‐initiated BUP. BUP administration: Initial BUP dose ranged from 2–16 mg (mode = 4). For continued withdrawal symptoms, 27 (87%) protocols recommended an interval of 30–60 minutes between first and second BUP dose. Total BUP dose in the ED ranged from 8 to 32 mg. Discharge care: Twenty‐eight (90%) protocols recommended a BUP prescription (mode 16 mg daily) at discharge. Naloxone prescription and/or provision was suggested in 23 (74%) protocols.ConclusionsIn this geographically diverse sample of EDs, protocols for ED‐initiated BUP differed between sites. Future work should evaluate the association between this variation and patient outcomes.

Delivering Transcutaneous Auricular Neurostimulation (Tan) to Improve Symptoms Associated with Opioid Withdrawal: Results from a Randomized, Controlled Trial

Background: The development of practical strategies for treatment of addiction is a major priority for government agencies and health plans given the substantial impact on health, social, and economic welfare. Recently, neurostimulation approaches have demonstrated efficacy managing opioid withdrawal symptoms (OWS). This investigation determined whether transcutaneous auricular neurostimulation (tAN) is safe and effective in management of OWS. Methods: Participants were followed during residential detox treatment (Austin, Texas) at a single center in the US in this randomized, participant and assessor-blinded, parallel group trial. Adult (18–65) participants with a history of opioid withdrawal were randomized 1:1 with sealed opaque envelopes, using permuted blocks of four to active tAN or delayed tAN. tAN was delivered up to 23 hours per day for five days at the following settings: 5 Hz, 250 μs, 1·0 mA at cymba concha and 100 Hz, 250 μs, 1·4 mA adjacently anterior to tragus. The hypothesis-driven primary outcome was change in opioid withdrawal symptoms, measured by the Clinical Opiate Withdrawal Scale (COWS), from baseline to 60 minutes after start of tAN therapy in the intention-to-treat (ITT) population. This study is registered with ClinicalTrials.gov (NCT04075214). Outcomes: Thirty-five (35) participants were enrolled between December 2019 and December 2020 and 31 of those were assigned equally to treatment. The primary endpoint analysis included all randomized participants. Mean (SD) COWS scores were significantly reduced by 7·0 (4·7) points at 60 minutes after start of tAN (95% CI, −4·2 to 9·7; p<0·0001; Cohen’s d=2·0), meaning the observed percent reduction in COWS score for the primary endpoint was both significant and clinically meaningful at 45·9%. Two participants (7·7%) experienced a device-related adverse event which resolved without intervention. Interpretation: Results provide relevant and statistical evidence of safe and effective use of tAN in reducing OWS and supported FDA clearance. Trial Registration: This study is registered with ClinicalTrials.gov (NCT04075214). Funding: Trial was funded by the Sponsor, Spark Biomedical. Declaration of Interest: NK, SW, DP, CB, HV and AC are employees of Spark Biomedical. CT has private equity (stock options or other ownership interest) in and is a paid consultant of Spark Biomedical. Ethical Approval: This trial was conducted in accordance with ICH Good Clinical Practices Guidelines (E6) and FDA regulations and followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines. Institutional Review Board (IRB) approval from Western Copernicus Group (20191239; Puyallup, WA) was obtained prior to study conduct

Percutaneous electrical nerve field stimulation to reduce clincial opiate withdrawal: a case series

ABSTRACT Background Medication-assisted treatment can reduce mortality and withdrawal symptoms, yet treatments can have side effects and are cost ineffective. Research has supported alternative approaches to withdrawal symptoms, specifically percutaneous nerve field stimulator (PNFS); yet, to date, there is a lack of understanding of the initial acceptability within treatment programs. Methods A retrospective case series evaluated PNFS to reduce opioid withdrawal symptoms for five adult patients participating in an in-home withdrawal management program. The device was worn for five consecutive days, in which a licensed practical nurses monitored their care. Evaluation included the clinical opiate withdrawal scale (COWS) and clinical reviews based on self-report and clinician interview. Results Significant reductions were noted for all five participants, with the average COWS score for Day 1 at 19.1 reducing to 2.6 at Day 5. In addition, 2-day post-COWS scores demonstrated a continual reduction to 1.4. Qualitative feedback from the patients was recorded, and generalized themes were recorded and addressed. Conclusions Future controlled, prospective studies should investigate the possibility that PNFS can significantly reduce negative symptoms of opiate withdrawal symptoms, along with providing alternatives to medication-assisted treatments for those who are suffering from opiate use disorder.

Interobserver agreement between emergency clinicians and nurses for Clinical Opiate Withdrawal Scale.

ObjectivesThe Clinical Opiate Withdrawal Scale (COWS) is a validated, commonly used tool to objectively quantify withdrawal symptoms, often in anticipation of treatment with buprenorphine. Our primary aim was to determine the agreement between emergency department (ED) nurses compared with emergency physicians in determining this score in ED patients who presented for opioid withdrawal treatment. Secondarily, we wanted to investigate the safety of buprenorphine induction in the ED setting.MethodsScoring for opioid withdrawal using the COWS was performed by ED clinicians and ED nurses independently on 120 patients. In addition to overall concordance, agreement (weighted kappa) was calculated between the 2 scores by various cutoffs: overall severity, COWS ≥ 5, and the 11 different individual measures. Patient documents also were reviewed for complications that could be possibly linked to buprenorphine induction.ResultsOur study sample of 120 subjects was 77% Hispanic and 78.3% male. The clinicians assigned a median interquartile range overall COWS score of 6 (2–12), which categorizes as mild withdrawal. Seventy‐eight (65%) subjects met the criteria of withdrawal (≥ 5 COWS) and 69 (58%) received an induction dose of buprenorphine (range 2 mg–24 mg) during the ED visit. No adverse effects or worsening withdrawal were reported. The overall observed concordance, based on severity withdrawal categorization, for all clinician pairs, was 67.5% (81/120) (95% confidence interval [CI], 58.7–75.2%). The weighted kappa for that concordance was 0.55 (95% CI, 0.43–0.67), giving a moderate strength of agreement. When data are dichotomized by COWS score ≥5, concordance was 82.5% (99/120) (95% CI, 74.7%–88.3%) and the weighted kappa was 0.65 (95% CI, 0.51–0.78), indicating substantial agreement. The breakdown by the 11 factors that constitute COWS showed only substantial agreement for pulse measurement.ConclusionThe agreement between ED clinicians and nurses for the overall COWS scoring in patients presenting for opioid withdrawal treatment was substantial. COWS scoring by ED nurses may help expedite treatment with buprenorphine on presentation.

Transition of Patients with Opioid Use Disorder from Buprenorphine to Extended-Release Naltrexone: A Randomized Clinical Trial Assessing Two Transition Regimens.

Background and ObjectiveWhen patients seek to discontinue buprenorphine (BUP) treatment, monthly injectable extended‐release naltrexone (XR‐NTX) may help them avoid relapse. The efficacy of low ascending doses of oral NTX vs placebo for patients transitioning from BUP to XR‐NTX is evaluated in this study.MethodsIn a phase 3, hybrid residential/outpatient study, clinically stable participants with opioid use disorder (N = 101), receiving BUP for more than or equal to 3 months and seeking antagonist treatment, were randomized (1:1) to 7 residential days of descending doses of BUP and low ascending doses of oral NTX (NTX/BUP, n = 50) or placebo (PBO‐N/BUP, n = 51). Both groups received standing ancillary medications and psychoeducational counseling. Following negative naloxone challenge, participants received XR‐NTX (day 8). The primary endpoint was the proportion of participants who received and tolerated XR‐NTX.ResultsThere was no statistical difference between groups for participants receiving a first dose of XR‐NTX: 68.6% (NTX/BUP) vs 76.0% (PBO‐N/BUP; P = .407). The mean number of days with peak Clinical Opiate Withdrawal Scale (COWS) score less than or equal to 12 during the treatment period (days 1‐7) was similar for NTX/BUP and PBO‐N/BUP groups (5.8 vs 6.3; P = .511). Opioid withdrawal symptoms during XR‐NTX induction and post‐XR‐NTX observation period (days 8‐11) were mild and similar between groups (mean peak COWS score: NTX/BUP, 5.1 vs PBO‐N/BUP, 5.4; P = .464). Adverse events were mostly mild/moderate.Conclusions and Scientific SignificanceLow ascending doses of oral NTX did not increase induction rates onto XR‐NTX compared with placebo. The overall rate of successful induction across treatment groups supports a brief BUP taper with standing ancillary medications as a well‐tolerated approach for patients seeking transition from BUP to XR‐NTX. (Am J Addict 2020;00:00–00)

Measuring Opioid Withdrawal in a Phase 3 Study of a New Analgesic, NKTR-181 (Oxycodegol), in Patients with Moderate to Severe Chronic Low Back Pain

ObjectiveTo evaluate the SUMMIT-07 trial opioid withdrawal results of NKTR-181 (oxycodegol), a new molecular entity mu-opioid receptor agonist.DesignPhase 3, enriched-enrollment, double-blind, randomized-withdrawal study in patients with chronic low back pain (CLBP).SettingConducted in the United States at multiple sites.MethodsSUMMIT-07 was comprised of five periods: screening; NKTR-181 open-label titration (100 to 400 mg twice daily); 12-week randomized, double-blind study drug (NKTR-181 or placebo); one-week study drug taper; and two-week safety follow-up. Permitted rescue medication included hydrocodone 5 mg/acetaminophen 300 mg (two tablets daily) for two weeks after randomization, then acetaminophen 1.0 gm daily for the remainder of the trial. Signs and symptoms of drug withdrawal were evaluated using the Clinical Opiate Withdrawal Scale (COWS); Subjective Opiate Withdrawal Scale (SOWS); Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS); and withdrawal-related adverse events.ResultsOf 1,190 patients entering titration, one patient had moderate withdrawal (COWS score 13/48 maximum) three days after discontinuing NKTR-181. Of 610 patients randomized (N = 309, NKTR-181; N = 301, placebo), no COWS scores indicating withdrawal at a moderate level or greater (i.e., score ≥13) were observed at any time point. At day 8 after randomization, week 12, and the end of tapering, COWS scores indicating mild withdrawal (<13) were observed in seven (2.4%), one (0.4%), and one (0.5%) placebo patients, respectively, and three (1.0%), one (0.4%), and five (2.3%) NKTR-181 patients, respectively. Mean SOWS scores in both arms were ≤2.8 of 64 possible points at all time points. During the randomized period, of 35 events identified by MADDERS, adjudicators identified 20 possible “withdrawal” events (9 [2.9%] NKTR-181 and 11 [3.7%] placebo).ConclusionsNKTR-181 exhibited a low rate and severity of opioid withdrawal in SUMMIT-07 patients with CLBP.

Opioid Withdrawal Precipitated by Long-Acting Antagonists.

Precipitated opioid withdrawal (POW) after opioid antagonist administration can be challenging to manage in the emergency department (ED), particularly if caused by a long-acting opioid antagonist such as naltrexone. There are no evidence-based guidelines to assist in safely and efficiently managing patients with this syndrome. To review current practice on the treatment of long-acting antagonist POW and make recommendations on the treatment of this complex disease process. A literature search of opioid withdrawal cases precipitated by naltrexone was done using PubMed. One of the authors screened all the results of this search by title and abstract, leading to a final count of 27 articles that were reviewed in full by all authors. English language cases that involved precipitated opioid withdrawal from a long-acting opioid antagonist were included. Data were extracted, including the precipitant involved and dose, severity of opioid withdrawal, treatments rendered, and response to treatment. In all cases where symptoms and signs were described, a Clinical Opiate Withdrawal Scale score was calculated based on the information available. Twenty-seven papers were included. Naltrexone alone was the primary antagonist reported in 19 of the papers, extended-release naltrexone in two, naltrexone-morphine combination in two, and nalmefene in four. Treatment most commonly included fluid replacement, benzodiazepines, antiemetics, and clonidine. Full opioid agonist treatment, although often suggested, was poorly described. Buprenorphine successfully reduced the severity and duration of withdrawal in several cases. No standardized response scale was used, and response to treatment ranged from 3 to 48h prior to resolution of clinical effects. Management of POW from long-acting antagonists is a complex problem with little formal evaluation of treatment options. There is not currently a sufficiently robust body of literature to support an evidence-based guideline. However, use of intravenous fluids, antiemetics, and benzodiazepines is commonly reported as successful and seems to be a reasonable approach until this process is better studied. A treatment strategy using partial agonists such as buprenorphine is emerging and may represent a safe and effective treatment pathway for these patients.