Characterizing acute and postsurgical pain management in patients receiving buprenorphine or buprenorphine/naloxone.

BACKGROUND: There is currently a clinical dilemma in treating acute pain in patients receiving long-term buprenorphine products. METHODS: This is a retrospective cohort review involving patients receiving long-term buprenorphine therapy who either underwent a surgical procedure or presented to an emergency department (ED) for acute pain between January 1, 2012 and January 1, 2022. Patients were excluded if opioids were prescribed 30 days before the index date. Chart reviews were conducted to characterize buprenorphine treatment strategies and the addition of new pain medications. Chart review revealed (1) incidence of opioid use disorder (OUD) relapse, (2) hospital re-presentation for pain or OUD, (3) fatal and non-fatal overdose, and (4) all-cause mortality and suicidality. Descriptive statistics were used to analyze results. RESULTS: A total of 70 of 259 screened patients met inclusion criteria. The mean (±SD) age was 50.3 ± 13 years, 92.9% male, 64.3% White, and 78.6% had an OUD diagnosis. While 84.3% presented to the ED, 15.7% underwent surgical procedures. For the primary endpoint, the total daily dose of buprenorphine or buprenorphine/naloxone from index date to discharge was continued in 90.0%, increased in 2.9%, decreased in 1.4%, and discontinued in 5.7% of cases. At discharge, 46.2% were prescribed an additional pain medication. A total of 7.1% re-presented for pain or OUD relapse, 15.7% experienced an OUD relapse, 1.4% experienced new-onset suicidality, and 1.4% experience all-cause mortality within 90 days of the index date. No fatal or non-fatal opioid overdoses were observed. CONCLUSION: The most commonly observed practice was continuing buprenorphine doses in patients with acute or postsurgical pain, which was effective and safe. Although further data is necessary to fully elucidate these findings, the data herein may suggest that clinicians can safely continue buprenorphine doses in the acute pain setting in patients receiving these products chronically.

Comparative Safety of In Utero Exposure to Buprenorphine Combined With Naloxone vs Buprenorphine Alone.

Importance: Buprenorphine combined with naloxone is commonly used to treat opioid use disorders outside of pregnancy. In pregnancy, buprenorphine alone is generally recommended because of limited perinatal safety data on the combination product. Objective: To compare perinatal outcomes following prenatal exposure to buprenorphine with naloxone vs buprenorphine alone. Design, Settings, and Participants: Population-based cohort study using health care utilization data from Medicaid-insured beneficiaries in the US from 2000 to 2018. The cohort was restricted to pregnant individuals linked to their liveborn infants, with maternal Medicaid enrollment from 3 months before pregnancy to 1 month after delivery and infant enrollment for the first 3 months after birth, unless they died sooner. Exposure: Use of buprenorphine with naloxone vs buprenorphine alone during the first trimester based on outpatient dispensings. Main Outcomes and Measures: Outcomes included major congenital malformations, low birth weight, neonatal abstinence syndrome, neonatal intensive care unit admission, preterm birth, respiratory symptoms, small for gestational age, cesarean delivery, and maternal morbidity. Confounder-adjusted risk ratios were calculated using propensity score overlap weights. Results: This study identified 3369 pregnant individuals exposed to buprenorphine with naloxone during the first trimester (mean [SD] age, 28.8 [4.6] years) and 5326 exposed to buprenorphine alone or who switched from the combination to buprenorphine alone by the end of the first trimester (mean [SD] age, 28.3 [4.5] years). When comparing buprenorphine combined with naloxone with buprenorphine alone, a lower risk for neonatal abstinence syndrome (absolute risk, 37.4% vs 55.8%; weighted relative risk, 0.77 [95% CI, 0.70-0.84]) and a modestly lower risk for neonatal intensive care unit admission (absolute risk, 30.6% vs 34.9%; weighted relative risk, 0.91 [95% CI, 0.85-0.98]) and small for gestational age (absolute risk, 10.0% vs 12.4%; weighted relative risk, 0.86 [95% CI, 0.75-0.98]) was observed. For maternal morbidity, the comparative rates were 2.6% vs 2.9%, respectively, and the weighted relative risk was 0.90 (95% CI, 0.68-1.19). No differences were observed with respect to major congenital malformations overall, low birth weight, preterm birth, respiratory symptoms, or cesarean delivery. Results were consistent across sensitivity analyses. Conclusions and Relevance: There were similar and, in some instances, more favorable neonatal and maternal outcomes for pregnancies exposed to buprenorphine combined with naloxone compared with buprenorphine alone. For the outcomes assessed, compared with buprenorphine alone, buprenorphine with naloxone during pregnancy appears to be a safe treatment option. This supports the view that both formulations are reasonable options for the treatment of opioid use disorder in pregnancy, affirming flexibility in collaborative treatment decision-making.

A Case Report: Rapid Micro-Induction of Buprenorphine/Naloxone to Administer Buprenorphine Extended-Release in an Adolescent With Severe Opioid Use Disorder.

BACKGROUND AND OBJECTIVES: Buprenorphine extended-release (BUP-XR) is a monthly injectable form of opioid agonist therapy. Before its administration, a minimum 7-day induction period with a transmucosal buprenorphine-containing product is recommended. METHODS: Case report (n = 1). RESULTS: A 16-year-old female with active, severe opioid use disorder (OUD) and stimulant use disorder, hepatitis C virus, co-occurring mental health disorders, and complex social stressors had five recent overdoses requiring naloxone. She had previously been treated with methadone and several trials of sublingual buprenorphine/naloxone, but would quickly discontinue the treatment. Using a rapid micro-induction protocol, buprenorphine/naloxone was administered for 3 days. On day 4, 300 mg BUP-XR was administered subcutaneously. Minimal withdrawal symptoms occurred, despite recent fentanyl use. DISCUSSION AND CONCLUSIONS: A rapid sublingual buprenorphine/naloxone micro-induction was successfully used to initiate BUP-XR, thereby eliminating the abstinence period prior to buprenorphine/naloxone administration, shortening the induction period, and minimizing withdrawal. SCIENTIFIC SIGNIFICANCE: This is the first reported case of using rapid micro-induction as a bridge to initiate BUP-XR. By reducing the length of induction to 4 days and minimizing withdrawal, this induction method can make BUP-XR more accessible to patients who would otherwise refuse the medication due to concerns of enduring withdrawal. (Am J Addict 2020;29:531-535).

Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX. METHODS: We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433. FINDINGS: Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group). INTERPRETATION: In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications. FUNDING: NIDA Clinical Trials Network.

Rapid micro-induction of buprenorphine/naloxone for opioid use disorder in an inpatient setting: A case series.

BACKGROUND AND OBJECTIVES: Buprenorphine/naloxone has been shown to be effective in the treatment of opioid use disorder. Due to its pharmacological properties, induction can be challenging, time-consuming, and result in sudden onset of withdrawal symptoms. METHODS: Retrospective case series (n = 2). RESULTS: Two patients with opioid use disorder were successfully started on buprenorphine/naloxone using a rapid micro-induction technique that did not cause precipitated withdrawal or require preceding cessation of other opioids. DISCUSSION AND CONCLUSIONS: These cases provide an alternative method for starting buprenorphine/naloxone that offers unique benefits compared to protocols previously described in the literature. SCIENTIFIC SIGNIFICANCE: This method can be used to minimize barriers to opioid agonist therapy. (Am J Addict 2019;28:262-265).

No increased pain among opioid-dependent individuals treated with extended-release naltrexone or buprenorphine-naloxone: A 3-month randomized study and 9-month open-treatment follow-up study.

BACKGROUND AND OBJECTIVES: It is presently unclear whether extended-release naltrexone hydrochloride treatment induces pain or aggravates existing pain among individuals with opioid use disorders. We assessed changes in pain among individuals receiving treatment with either extended-release naltrexone hydrochloride or buprenorphine-naloxone hydrochloride. METHODS: This randomized prospective open-label clinical study included 143 participants (aged 18-60 years) with opioid dependencies, recruited from outpatient addiction clinics at five urban hospitals in Norway. After in-patient detoxification from opioids, patients were randomized to 12-week treatment with either long-acting naltrexone (380 mg intramuscularly injected every four weeks) or buprenorphine-naloxone (flexible 4-16 mg sublingual doses daily). This phase was followed by a 9-month open-treatment study with the participant's choice of either naltrexone or buprenorphine-naloxone. Changes in pain were assessed every 4 weeks using the Norwegian Short-Form of McGill Pain Questionnaire. RESULTS: Throughout the study period, we found no increase in mean sensory pain, affective pain, or present pain intensity on the McGill Pain Questionnaire, in either treatment group, including the subgroups of participants with chronic pain. Participants who switched from buprenorphine-naloxone to extended-release naltrexone treatment after week 12 reported no increase in pain intensity during longer-term treatment. Women experienced significantly more affective pain symptoms than men (p = .01). DISCUSSION AND CONCLUSIONS: Among individuals with opioid use disorder, switching from daily opioid use to long-acting naltrexone did not induce pain, or aggravate mild-to-moderate chronic pain. SCIENTIFIC SIGNIFICANCE: In opioid-dependent individuals, mild-to-moderate chronic pain was not influenced by opioid agonist or antagonist treatment. TRIAL REGISTRATION: Clinicaltrials.gov #NCT01717963, first registered: Oct 28, 2012. Protocol version # 3C, June 12th 2012. (Am J Addict 2018;XX:1-9).

Perioperative opioid requirements of patients receiving sublingual buprenorphine-naloxone: a case series.

BACKGROUND: Buprenorphine, a partial opioid agonist, displaces full opioid agonists from receptors and may impede surgical pain management. We report the effects of a sublingual formulation of buprenorphine-naloxone, Suboxone (SL-BUP), on perioperative pain management. METHODS: We identified all adult surgical patients from December 31, 2004, to January 1, 2016, who received SL-BUP within 30 days prior to procedures performed with general, regional, or combined general/regional anesthesia. We recorded opioid use during the procedure, in the post-anesthesia care unit (PACU), and during the 24 h following PACU discharge. We also examined opioid use in those who continued SL-BUP until the day of surgery vs those who preoperatively discontinued SL-BUP. RESULTS: Thirty-two patients were treated preoperatively with SL-BUP. Three patients had regional anesthesia only, and opioid requirements were case dependent. Requirements were minimal for creation of an arteriovenous fistula and high following knee replacement and cesarean section. Twelve patients received combined general/regional anesthesia, and 17 received general anesthesia only. Intraoperative and PACU opioid use in these 2 groups were not significantly different (P = .10 and P = .93, respectively). In both groups opioid use increased after discharge from the PACU, and remained comparable between the general and combined general/regional group through the first 24 h after PACU discharge (P = .78). Although median [interquartile range] 24-h opioid doses were higher among patients who discontinued SL-BUP, the difference was not statistically significant in the general anesthesia-only group (SL-BUP discontinued, 199 [110-411] mg IV-MEq [intravenous morphine equivalent] vs SL-BUP continued, 106 [58-160] mg IV-MEq; P = .15) or in the combined general/regional group (SL-BUP discontinued, 140 [100-157] mg IV-MEq vs SL-BUP continued, 100 [73-203] mg IV-MEq; P = .94). CONCLUSIONS: Regardless of the type of anesthesia used, physicians treating patients with SL-BUP must be prepared to administer large doses of opioids during the early postoperative period. No difference in opioid requirements was noted between patients who perioperatively stopped SL-BUP versus those who continued SL-BUP.

Intravenous Misuse of Methadone, Buprenorphine and Buprenorphine-Naloxone in Patients Under Opioid Maintenance Treatment: A Cross-Sectional Multicentre Study.

BACKGROUND: The act of intravenous misuse is common in patients under opioid maintenance treatment (OMT), but information on associated factors is still limited. OBJECTIVES: To explore factors associated with (a) intravenous OMT misuse, (b) repeated misuse, (c) emergency room (ER) admission, (d) misuse of different OMT types and (e) concurrent benzodiazepine misuse. METHODS: We recruited 3,620 patients in 27 addiction units in Italy and collected data on the self-reported rate of intravenous injection of methadone (MET), buprenorphine (BUP), BUP-naloxone (NLX), OMT dosage and type, experience of and reason for misuse, concurrent intravenous benzodiazepine misuse, pattern of -misuse in relation to admission to the addiction unit and ER -admissions because of misuse. According to inclusion/exclusion criteria, 2,585 patients were included. RESULTS: Intravenous misuse of OMT substances was found in 28% of patients with no difference between OMT types and was associated with gender, age, type of previous opioid abuse and intravenous benzodiazepine misuse. Repeated OMT misuse was reported by 20% (i.e., 71% of misusers) of patients and was associated with positive OMT misuse experience and intravenous benzodiazepine misuse. Admission to the ER because of misuse complications was reported by 34% of patients, this outcome being associated with gender, employment, type of previous opioid abuse and intravenous benzodiazepine misuse. OMT dosage was lower than the recommended maintenance dosage. CONCLUSIONS: We offered new information on factors associated with intravenous OMT misuse, repeated misuse and ER admission in Italian patients under OMT. Our data indicate that BUP-NLX misuse is not different from that of BUP or MET. Choosing the more expensive BUP-NLX over MET will likely not lead to the expected reduction of the risk of injection misuse of the OMT. Instead of prescribing new and expensive OMT formulations, addiction unit physicians and medical personnel should better focus on patient's features that are associated with a higher likelihood of misuse. Care should be paid to concurrent benzodiazepine and OMT misuse.

Are the Patients Ready for the Change?: An Empirical Study to Evaluate the Impact of Change in Formulation of Buprenorphine-Naloxone on Prescription Pattern, Treatment Adherence, and Patient Satisfaction.

BACKGROUND: Therapeutic adherence is one of the most important determinants of the outcome with OST. There are no published studies that have explored the impact of change in tablet formulation of buprenorphine-naloxone from one brand to another among patients receiving OST. OBJECTIVES: The current study is aimed at evaluation of the impact of change in buprenorphine-naloxone formulation on prescription pattern, treatment adherence, and patient satisfaction with OST. METHODS: Our study was a cross sectional study based on a cohort of patients who were receiving OST at the study setting. Changes in prescription pattern, reports of subjective opioid withdrawal symptoms, or observation of objective opioid withdrawal symptoms were noted from the case records. The satisfaction and concerns of the patients with buprenorphine-naloxone formulations were assessed using a semi-structured proforma. RESULTS: An increase in dose of buprenorphine-naloxone was noted in 22 participants, since formulation change. Twenty participants reported that the color of the formulation was different from the previous one, the intensity of effect was reported to be different by 87% participants. Seventy-three percent participants endorsed that increase in dose can be a possible solution to address the perceived differences in the effects of two formulations. Changes in physical attributes of the formulation, perception among treatment seeking peers regarding such changes in treatment, and lack of sense of autonomy regarding one's treatment play a more important role in determining response of the patients to changes in formulation of buprenorphine-naloxone.

Methadone to buprenorphine/naloxone induction without withdrawal utilizing transdermal fentanyl bridge in an inpatient setting-Azar method.

BACKGROUND AND OBJECTIVES: Although buprenorphine/naloxone is widely recognized as first-line therapy for opioid use disorder, the requirement for moderate withdrawal prior to initiation in efforts to avoid precipitated withdrawal can be a barrier to its initiation. METHODS: We present a case utilizing transdermal fentanyl as a bridging treatment to eliminate withdrawal during the transition from methadone to buprenorphine/naloxone in a patient who had ongoing significant intravenous heroin use while on methadone. RESULTS: Patient was successfully transitioned from methadone to buprenorphine/naloxone without a period of withdrawal utilizing transdermal fentanyl as a bridge in an inpatient setting. DISCUSSION AND CONCLUSIONS: Our experience indicates a transdermal depot of fentanyl allows for slow release and elimination while buprenorphine doses are introduced during an induction without presence of withdrawal, as quantified by serial clinical opiate withdrawal score. SCIENTIFIC SIGNIFICANCE: This case report highlights ways to minimize barriers to induction of first-line opioid substitution therapy, buprenorphine/naloxone, by eliminating withdrawal during induction phase utilizing a fentanyl bridge within the limitations of a transdermal fentanyl bridge in an inpatient setting. (Am J Addict 2018;XX:1-4).

Case Series of Successful Postoperative Pain Management in Buprenorphine Maintenance Therapy Patients.

Buprenorphine maintenance therapy patients frequently have severe postoperative pain due to buprenorphine-induced hyperalgesia and provider use of opioids with limited efficacy in the presence of buprenorphine. The authors report good-to-excellent pain management in 4 obstetric patients using nonopioid analgesics, regional anesthesia, continuation of buprenorphine, and use of opioids with high µ receptor affinity.

Peripartum Anesthetic Management of the Opioid-tolerant or Buprenorphine/Suboxone-dependent Patient.

Opioid abuse and dependence continues to rise in both the general population and pregnancy, with opioid overdose deaths having quadrupled in the last 15 years. Illicit drug use in last 30 days of pregnancy was over 4% with almost 0.6% documented maternal opiate use at time of birth. The management of the opioid-tolerant, buprenorphine-dependent or methadone-dependent patient in the peripartum period is reviewed. Options for treatment of opioid dependence, acute pain management, and perioperative multimodal analgesia are discussed. The effects of maternal management on neonatal abstinence syndrome are also reviewed.

Association Between Sublingual Buprenorphine-Naloxone Exposure and Dental Disease.

This study examines the association of sublingual buprenorphine/naloxone and dental adverse events using the IQVIA health claims database.

New psychoactive substances as part of polydrug abuse within opioid maintenance treatment revealed by comprehensive high-resolution mass spectrometric urine drug screening.

OBJECTIVE: At present, polydrug abuse comprises, besides traditional illicit drugs, new psychoactive substances (NPS) and non-prescribed psychotropic medicines (N-PPM). Polydrug abuse was comprehensively evaluated among opioid-dependent patients undergoing opioid maintenance treatment (OMT). METHODS: Two hundred consecutively collected urine samples from 82 OMT patients (52 male) treated with methadone or buprenorphine-naloxone medication were studied using a liquid chromatography/time-of-flight mass spectrometry screening method. The method enables simultaneous detection of hundreds of abused substances covering the traditional drugs of abuse and many NPS as well as N-PPM. RESULTS: Ninety-two (45.8%) samples were positive for the abused substances. Benzodiazepines (29.0%), amphetamines (19.5%), cannabinoids (17.0%), NPS (13.0%), N-PPM (9.0%), and opioids (9.0%) were detected in different combinations. The simultaneous occurrence of up to three groups of abused substances was common (40.0%), and in one sample, all six groups were found. The stimulant NPS alpha-pyrrolidinovalerophenone was found in 10.0% and the sedative N-PPM pregabalin in 4.0% of the samples. The patients were seldom aware of what particular NPS they had abused. CONCLUSIONS: A widespread occurrence of abused substances beyond the ordinary was revealed. Identifying these patients is essential as polydrug abuse is a safety risk to the patient and may cause attrition from OMT.

Abuse potential of intranasal buprenorphine versus buprenorphine/naloxone in buprenorphine-maintained heroin users.

In spite of the clinical utility of buprenorphine, parenteral abuse of this medication has been reported in several laboratory investigations and in the real world. Studies have demonstrated lower abuse liability of the buprenorphine/naloxone combination relative to buprenorphine alone. However, clinical research has not yet examined the utility of the combined formulation to deter intranasal use in a buprenorphine-maintained population. Heroin-using volunteers (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three sublingual buprenorphine doses (2, 8, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intranasal doses of buprenorphine (8, 16 mg), buprenorphine/naloxone (8/2, 8/8, 8/16, 16/4 mg) and controls (placebo, heroin 100 mg, naloxone 4 mg) were assessed. Intranasal buprenorphine alone typically produced increases in positive subjective effects and the 8 mg dose was self-administered above the level of placebo. The addition of naloxone dose dependently reduced positive subjective effects and increased aversive effects. No buprenorphine/naloxone combination dose was self-administered significantly more than placebo. These data suggest that within a buprenorphine-dependent population, intranasal buprenorphine/naloxone has reduced abuse potential in comparison to buprenorphine alone. These data strongly argue in favor of buprenorphine/naloxone rather than buprenorphine alone as the more reasonable option for managing the risk of buprenorphine misuse.

Reversal of overdose on fentanyl being illicitly sold as heroin with naloxone nasal spray: A case report.

BACKGROUND: This is a case report describing a reversal of fentanyl overdose with naloxone nasal spray. The patient was not aware that he overdosed on fentanyl being sold as heroin. METHODS: The Veterans Health Administration (VHA) has implemented an initiative to provide education for veterans, their families, friends and significant others about opioid overdose and use of naloxone reversal kits. The Atlanta VA Medical Center adopted this program to reduce the risk of opioid overdose in high risk patients. RESULTS: Over the past year, we provided educational sessions for 63 veterans and their families. We also prescribed 41 naloxone kits. We have received three reports of opioid overdose reversal with use of naloxone kits prescribed by the Atlanta VA Medical Center. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The authors recommend that public health administrators and policy makers advocate for the implementation of these programs to reduce the rising number of overdose death in the United States and worldwide.

Treatment outcomes in opioid dependent patients with different buprenorphine/naloxone induction dosing patterns and trajectories.

BACKGROUND AND OBJECTIVES: Induction is a crucial period of opioid addiction treatment. This study aimed to identify buprenorphine/naloxone (BUP) induction patterns and examine their association with outcomes (opioid use, retention, and related adverse events [AEs]). METHODS: The secondary analysis of a study of opioid-dependent adults seeking treatment in eight treatment settings included 740 participants inducted on BUP with flexible dosing. RESULTS: Latent class analysis models detected six distinctive induction trajectories: bup1-started and remained on low; bup2-started low, shifted slowly to moderate; bup3-started low, shifted quickly to moderate; bup4-started high, shifted to low; bup5-started and remained on moderate; bup6-started moderate, shifted to high dose (Fig. 1). Baseline characteristics, including Clinical Opioid Withdrawal Scale (COWS), were important predictors of retention. When controlled for the baseline characteristics, bup6 participants were three times less likely to drop out the first 7 days than bup1 participants (adjusted hazard ratio (aHR) = .28, p = .03). Opioid use and AEs were similar across trajectories. Participants on ≥16 mg BUP compared to those on <16 mg at Day 28 were less likely to drop out (aHR = .013, p = .001) and less likely to have AEs during the first 28 days (aOR = .57, p = .03). DISCUSSION AND CONCLUSIONS: BUP induction dosing was guided by an objective measure of opioid withdrawal. Participants with higher baseline COWS whose BUP doses were raised more quickly were less likely to drop out in the first 7 days than those whose doses were raised slower. SCIENTIFIC SIGNIFICANCE: This study supports the use of an objective measure of opioid withdrawal (COWS) during BUP induction to improve retention early in treatment.