Extended-Release 7-Day Injectable Buprenorphine for Patients With Minimal to Mild Opioid Withdrawal
07/2024
Journal Article
Authors:
D'Onofrio, G.;
Herring, A. A.;
Perrone, J.;
Hawk, K.;
Samuels, E. A.;
Cowan, E.;
Anderson, E.;
McCormack, R.;
Huntley, K.;
Owens, P.;
Martel, S.;
Schactman, M.;
Lofwall, M. R.;
Walsh, S. L.;
Dziura, J.;
Fiellin, D. A.
Volume:
7
Pagination:
e2420702
Issue:
7
Journal:
JAMA Netw Open
PMID:
38976265
URL:
https://www.ncbi.nlm.nih.gov/pubmed/38976265
DOI:
10.1001/jamanetworkopen.2024.20702
Keywords:
Adult Female Humans Male Middle Aged Analgesics, Opioid/administration & dosage/therapeutic use *Buprenorphine/administration & dosage/therapeutic use *Delayed-Action Preparations Feasibility Studies
Narcotic Antagonists/administration & dosage/therapeutic use Opiate Substitution Treatment/methods *Opioid-Related Disorders/drug therapy *Substance Withdrawal Syndrome/drug therapy
Abstract:
IMPORTANCE: Buprenorphine is an effective yet underused treatment for opioid use disorder (OUD). OBJECTIVE: To evaluate the feasibility (acceptability, tolerability, and safety) of 7-day injectable extended-release buprenorphine in patients with minimal to mild opioid withdrawal. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTION: Injection of a 24-mg dose of a weekly extended-release formulation of buprenorphine (CAM2038) and referral for ongoing OUD care. MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04225598.
