{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T16:18:14Z","timestamp":1777738694031,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01DA056407"],"award-info":[{"award-number":["R01DA056407"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To estimate the effectiveness of different thresholds for administering opioid withdrawal medications (clonidine and clonazepam) on the probability of successfully initiating extended\u2010release naltrexone (XR\u2010NTX) among participants with opioid use disorder (OUD) during medically managed withdrawal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Secondary analysis of a multisite clinical trial comparing a rapid vs. standard approach for XR\u2010NTX initiation, 2021\u20132022.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Six community inpatient addiction treatment units in the United States.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>\n                      English\u2010speaking adults seeking treatment for DSM\u20105 OUD and expressing interest in XR\u2010NTX treatment (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009415).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>We estimated the extent to which the following thresholds for adjunctive medication administration would affect the probability of initiating XR\u2010NTX over time: 1) where adjunctive medications were given in response to at mild\u2010to\u2010moderate withdrawal symptoms or greater [Clinical Opiate Withdrawal Scale (COWS) score \u2265 5), 2) where adjunctive medications were given in response to minimal withdrawal symptoms or greater (COWS score \u2265 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\u2010NTX initiation under each of these three treatment regimes while accounting for dropout and initiation of other medications as competing events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>The estimated probability of initiating XR\u2010NTX by day 14 was 50.4% [95% confidence interval (CI) = 41.8\u201358.9) under the no\u2010threshold regime, 43.9% (95% CI = 39.1\u201348.7) under the regime of waiting for minimal withdrawal symptoms and 38.5% (95% CI = 34.3\u201342.6) under the regime of waiting for mild\u2010to\u2010moderate withdrawal symptoms. Probability of XR\u2010NTX initiation was a statistically significant 11.9 percentage points higher (95% CI = 3.6\u201320.2) under the no\u2010threshold regime versus the mild\u2010to\u2010moderate threshold regime, and a non\u2010statistically significant 6.4 percentage points (95% CI = \u22120.8 to 13.7) higher under the no\u2010threshold regime versus the minimal\u00a0threshold regime.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Providing clonidine and clonazepam daily during the first five days of medically managed opioid withdrawal appears to statistically significantly increase the likelihood of initiating extended\u2010release naltrexone treatment compared with waiting for mild\u2010to\u2010moderate 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/add.70189","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T04:51:28Z","timestamp":1758171088000},"page":"117-125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Thresholds for adjunctive medication usage and probability of initiating injectable naltrexone"],"prefix":"10.1111","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9417-7960","authenticated-orcid":false,"given":"Kara E.","family":"Rudolph","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Mailman School of Public Health Columbia University  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shodai","family":"Inose","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Mailman School of Public Health Columbia University  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas T.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Mailman School of Public Health Columbia University  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iv\u00e1n","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Division of Biostatistics New York University Grossman School of Medicine  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2049-6918","authenticated-orcid":false,"given":"Rachael K.","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Mailman School of Public Health Columbia University  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Bisaga","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Columbia University  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2941-8895","authenticated-orcid":false,"given":"Matisyahu","family":"Shulman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Columbia University  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadr.2022.100052"},{"key":"e_1_2_11_3_1","unstructured":"Centers for Disease Control and Prevention (CDC).Overdose deaths involving psychostimulants on the rise.2024[cited 2024 Dec 11].https:\/\/www.cdc.gov\/nchs\/pressroom\/nchs_press_releases\/2024\/20240515.htm"},{"issue":"3","key":"e_1_2_11_4_1","article-title":"Opioid use disorder","volume":"6","author":"Strang J","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7325a1"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.14180"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32812-X"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.9744"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.15836"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2016.16050548"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsat.2021.108292"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/00952990.2011.653426"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13722-021-00277-z"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/02791072.2003.10400007"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2009.07.001"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8471"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-statistics-022513-115553"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10985-023-09606-7"},{"issue":"1","key":"e_1_2_11_19_1","article-title":"Super learner","volume":"6","author":"Laan MJ","year":"2007","journal-title":"Stat Appl Genet Mol Biol"},{"key":"e_1_2_11_20_1","unstructured":"MilborrowS HastieT TibshiraniR.earth: Multivariate Adaptive Regression Splines. 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