Evidence map›Paper›PMID 40963369›Full record

Trial reportAddiction (Abingdon, England)2026

Thresholds for adjunctive medication usage and probability of initiating injectable naltrexone.

Kara E Rudolph, Shodai Inose, Nicholas T Williams, Iván Díaz, Rachael K Ross, Adam Bisaga, Matisyahu Shulman

Abstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Addiction (Abingdon, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Kara E RudolphDepartment of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.ORCID 0000-0002-9417-7960
Shodai InoseDepartment of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Nicholas T WilliamsDepartment of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Iván DíazDivision of Biostatistics, New York University Grossman School of Medicine, New York, NY, USA.
Rachael K RossDepartment of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.ORCID 0000-0002-2049-6918
Adam BisagaDepartment of Psychiatry, Columbia University, New York, NY, USA.
Matisyahu ShulmanDepartment of Psychiatry, Columbia University, New York, NY, USA.ORCID 0000-0002-2941-8895

Funding

Project-003UG1DA013035 · NIDA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Aimee N Campbell, Jennifer McNeely · 2015 to 2026
$130.3M
Design and analysis advances to improve generalizability of clinical trials for treating opioid use disorderR01DA056407 · NIDA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Kara Elizabeth Rudolph, Elizabeth A. Stuart · 2022 to 2026
$3.1M
NIDA NIH HHS R01 DA056407NIDA NIH HHS R01DA056407NIDA NIH HHS UG1 DA013035Patient Centered Outcomes Research Institute ME-2021C2-23636
6 · The paper itself

Abstract

aimsTo estimate the effectiveness of different thresholds for administering opioid withdrawal medications (clonidine and clonazepam) on the probability of successfully initiating extended-release naltrexone (XR-NTX) among participants with opioid use disorder (OUD) during medically managed withdrawal.

designSecondary analysis of a multisite clinical trial comparing a rapid vs. standard approach for XR-NTX initiation, 2021-2022.

settingSix community inpatient addiction treatment units in the United States.

participantsEnglish-speaking adults seeking treatment for DSM-5 OUD and expressing interest in XR-NTX treatment (n = 415). MEASUREMENTS: We estimated the extent to which the following thresholds for adjunctive medication administration would affect the probability of initiating XR-NTX over time: 1) where adjunctive medications were given in response to at mild-to-moderate withdrawal symptoms or greater [Clinical Opiate Withdrawal Scale (COWS) score ≥ 5), 2) where adjunctive medications were given in response to minimal withdrawal symptoms or greater (COWS score ≥ 3) and 3) where adjunctive medications were given regardless of withdrawal symptoms. Using a longitudinal sequentially doubly robust estimator, we estimated the cumulative probability of XR-NTX initiation under each of these three treatment regimes while accounting for dropout and initiation of other medications as competing events.

findingsThe estimated probability of initiating XR-NTX by day 14 was 50.4% [95% confidence interval (CI) = 41.8-58.9) under the no-threshold regime, 43.9% (95% CI = 39.1-48.7) under the regime of waiting for minimal withdrawal symptoms and 38.5% (95% CI = 34.3-42.6) under the regime of waiting for mild-to-moderate withdrawal symptoms. Probability of XR-NTX initiation was a statistically significant 11.9 percentage points higher (95% CI = 3.6-20.2) under the no-threshold regime versus the mild-to-moderate threshold regime, and a non-statistically significant 6.4 percentage points (95% CI = -0.8 to 13.7) higher under the no-threshold regime versus the minimal threshold regime.

conclusionsProviding clonidine and clonazepam daily during the first five days of medically managed opioid withdrawal appears to statistically significantly increase the likelihood of initiating extended-release naltrexone treatment compared with waiting for mild-to-moderate withdrawal symptoms to administer adjunctive medications. To improve initiation rates, providers may consider lowering the threshold at which they provide adjunctive medications, giving these medications preemptively or to manage even minimal withdrawal symptoms.

Indexed as

ClonidineNaltrexoneNarcotic AntagonistsOpioid-Related DisordersSubstance Withdrawal SyndromeAdultDelayed-Action PreparationsDrug Therapy, CombinationFemaleHumansMaleMiddle AgedUnited StatesClonidineDelayed-Action PreparationsNaltrexoneNarcotic Antagonistsclonazepamclonidineinjectable naltrexoneMOUDopioid use disorderwithdrawal symptoms

Identifiers

PMID40963369
PMCPMC12448091

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.