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Differences in opioid withdrawal severity that predict treatment outcome could facilitate the process of matching patients to treatments. This is a secondary analysis of a randomized controlled trial (RCT) that enrolled treatment seeking heroin\u2010users (N = 89, males = 78) into a residential study. Participants maintained on morphine (30\u00a0mg, subcutaneous, four\u2010times daily) underwent a naloxone (0.4\u00a0mg, IM = intramuscular) challenge session to precipitate withdrawal. Area\u2010under\u2010the\u2010curve (AUC) values from self\u2010reported withdrawal ratings during the challenge session were analyzed using <jats:italic>K<\/jats:italic>\u2010means clustering, revealing two phenotype groups. Withdrawal and retention from the subsequent 14\u2010day double\u2010blind, double\u2010dummy RCT comparing three study medications (clonidine, tramadol\u2010ER, and buprenorphine) were evaluated as a function of phenotype. Cluster analyses suggested HIGH (N\u00a0=\u00a037; mean [SD] subjective opiate withdrawal scale [SOWS]\u2013AUC 123.7 [65.8]) and LOW (N\u00a0=\u00a052; SOWS\u2010AUC 68.0 [47.7]) withdrawal phenotype groups. HIGH participants were significantly more female and had lower body mass indices than LOW participants; no drug\u2010use variables were significant. Regarding RCT outcomes, HIGH phenotype participants were less likely to be retained in the study (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.02) and had higher mean self\u2010reported withdrawal (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.05) than LOW phenotype participants. A significant interaction in RCT retention was observed between phenotype (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.02) and study medication (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). Self\u2010reported withdrawal was significant for phenotype (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.02); study medication trended towards significance (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.07). Results suggest patients have meaningfully different experiences of opioid withdrawal that may predict differential response to opioid pharmacotherapies during supervised withdrawal. Additional prospective research to replicate and more thoroughly evaluate withdrawal phenotype correlates and sex differences is warranted.<\/jats:p>","DOI":"10.1111\/adb.12680","type":"journal-article","created":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T10:25:18Z","timestamp":1538994318000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Preliminary evidence of different and clinically meaningful opioid withdrawal phenotypes"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3746-3108","authenticated-orcid":false,"given":"Kelly E.","family":"Dunn","sequence":"first","affiliation":[{"name":"Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise M.","family":"Weerts","sequence":"additional","affiliation":[{"name":"Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.","family":"Huhn","sequence":"additional","affiliation":[{"name":"Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer R.","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2112-2299","authenticated-orcid":false,"given":"David Andrew","family":"Tompkins","sequence":"additional","affiliation":[{"name":"Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George E.","family":"Bigelow","sequence":"additional","affiliation":[{"name":"Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Strain","sequence":"additional","affiliation":[{"name":"Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,8]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Substance Abuse and Mental Health Services Administration (SAMHSA)(2014)National survey of substance abuse treatmetn services (N\u2010SSATS): 2013. 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