{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:22:34Z","timestamp":1791321754093,"version":"4.3.1"},"reference-count":78,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T00:00:00Z","timestamp":1703548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A re\u2010examination of clinical principles of long\u2010term opioid therapy (LTOT) for chronic pain is long overdue amid the ongoing opioid crisis. Most patients on LTOT report ineffectiveness (poor pain control, function and health) but still find deprescribing challenging. Although prescribed as analgesics, opioids more likely provide pain relief primarily through reward system actions (enhanced relief and motivation) and placebo effect and less through antinociceptive effects. The unavoidable physiologic LTOT dependence can automatically lead to a paradoxical worsening of pain, disability and medical instability (maladaptive opioid dependence) without addiction due to allostatic opponent neuroadaptations involving reward\/antireward and nociceptive\/antinociceptive systems. This opioid\u2010induced chronic pain syndrome (OICP) can persist\/progress whether LTOT dose is maintained at the same level, increased, decreased or discontinued. Current conceptualization of LTOT as a straightforward long\u2010term analgesic therapy appears incongruous in view of the complex mechanisms of opioid action, LTOT dependence and OICP. LTOT can be more appropriately conceptualized as therapeutic induction and maintenance of an <jats:italic>adaptive<\/jats:italic> LTOT dependence for functional improvement irrespective of analgesic benefits. Adaptive LTOT dependence should be ideally used for a limited time to achieve maximum functional recovery and deprescribed while maintaining functional gains. Patients on LTOT should be regularly re\u2010evaluated to identify if maladaptive LTOT dependence with OICP has diminished any functional gains or leads to ineffectiveness. Ineffective LTOT (with maladaptive LTOT dependence) should be modified to make it safer and more effective. An adequately functional life without opioids is the ideal healthy long\u2010term goal for both LTOT initiation and LTOT modification.<\/jats:p>","DOI":"10.1111\/bcp.15972","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T13:01:14Z","timestamp":1700658074000},"page":"2962-2976","source":"Crossref","is-referenced-by-count":14,"title":["Are opioids effective analgesics and is physiological opioid dependence benign? Revising current assumptions to effectively manage long\u2010term opioid therapy and its deprescribing"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9208-1490","authenticated-orcid":false,"given":"Ajay","family":"Manhapra","sequence":"first","affiliation":[{"name":"Section of Pain Medicine, Department of Physical Medicine &amp; Rehabilitation Sciences Hampton VA Medical Center  Hampton Virginia USA"},{"name":"New England Mental Illness Research Education and Clinical Center  West Haven Connecticut USA"},{"name":"Department of Psychiatry Yale School of Medicine  New Haven Connecticut USA"},{"name":"Departments of Physical Medicine and Rehabilitation and Psychiatry Eastern Virginia Medical School  Norfolk Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8067-7828","authenticated-orcid":false,"given":"R. Ross","family":"MacLean","sequence":"additional","affiliation":[{"name":"New England Mental Illness Research Education and Clinical Center  West Haven Connecticut USA"},{"name":"Department of Psychiatry Yale School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Rosenheck","sequence":"additional","affiliation":[{"name":"New England Mental Illness Research Education and Clinical Center  West Haven Connecticut USA"},{"name":"Department of Psychiatry Yale School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Becker","sequence":"additional","affiliation":[{"name":"Program in Addiction Medicine Yale School of Medicine  New Haven Connecticut USA"},{"name":"Pain Research, Informatics, Multimorbidities &amp; Education Center of Innovation VA Connecticut Healthcare System  West Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,26]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2023.03.008"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2012.3212"},{"key":"e_1_2_17_4_1","first-page":"1","article-title":"New addiction criteria: diagnostic challenges persist in treating pain with opioids","volume":"1","author":"Ballantyne JC","year":"2013","journal-title":"Pain"},{"key":"e_1_2_17_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/08897077.2017.1381663"},{"key":"e_1_2_17_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.4278"},{"key":"e_1_2_17_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0230751"},{"key":"e_1_2_17_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325\u2010019\u201001200\u20104"},{"key":"e_1_2_17_9_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.rr6501e1"},{"key":"e_1_2_17_10_1","unstructured":"ChouR HartungD TurnerJ et al.Opioid treatments for chronic pain [internet]\u2014comparative effectiveness review no. 229. Accessed November 9 2023.https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK556253\/?report=classic. Rockville MD:Agency for Healthcare Research and Quality (US);2020."},{"key":"e_1_2_17_11_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.rr7103a1"},{"key":"e_1_2_17_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(23)00404\u2010X"},{"key":"e_1_2_17_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(16)31494\u20105"},{"key":"e_1_2_17_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(16)00652\u20108"},{"key":"e_1_2_17_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2020.108291"},{"key":"e_1_2_17_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2010.450"},{"key":"e_1_2_17_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.7789"},{"key":"e_1_2_17_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.1742"},{"key":"e_1_2_17_19_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.21070721"},{"key":"e_1_2_17_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/pm\/pnw078"},{"key":"e_1_2_17_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2018.09.001"},{"key":"e_1_2_17_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002336"},{"key":"e_1_2_17_23_1","doi-asserted-by":"publisher","DOI":"10.7326\/M15\u20100038"},{"key":"e_1_2_17_24_1","doi-asserted-by":"publisher","DOI":"10.7326\/M17\u20100598"},{"key":"e_1_2_17_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606\u2010020\u201006253\u20108"},{"key":"e_1_2_17_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsat.2019.05.001"},{"key":"e_1_2_17_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5581"},{"key":"e_1_2_17_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m283"},{"key":"e_1_2_17_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606\u2010019\u201005227\u20109"},{"key":"e_1_2_17_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.16726"},{"key":"e_1_2_17_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.2613"},{"key":"e_1_2_17_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002298"},{"key":"e_1_2_17_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.15689"},{"key":"e_1_2_17_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606\u2010019\u201005301\u20102"},{"key":"e_1_2_17_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.11013"},{"key":"e_1_2_17_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2020.108248"},{"key":"e_1_2_17_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0232538"},{"key":"e_1_2_17_38_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.9191"},{"key":"e_1_2_17_39_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.46697"},{"key":"e_1_2_17_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/08897077.2016.1261070"},{"key":"e_1_2_17_41_1","doi-asserted-by":"publisher","DOI":"10.7326\/M21-3042"},{"key":"e_1_2_17_42_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1904190"},{"key":"e_1_2_17_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41394\u2010018\u20100092\u20105"},{"key":"e_1_2_17_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864\u2010022\u201000985\u2010x"},{"key":"e_1_2_17_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1507136"},{"key":"e_1_2_17_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103959(85)90172\u20101"},{"key":"e_1_2_17_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100441"},{"key":"e_1_2_17_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2005.05.008"},{"key":"e_1_2_17_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103959(85)90026\u20100"},{"key":"e_1_2_17_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000798"},{"key":"e_1_2_17_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3811"},{"key":"e_1_2_17_52_1","doi-asserted-by":"publisher","DOI":"10.1037\/amp0000632"},{"key":"e_1_2_17_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/pm\/pnz249"},{"key":"e_1_2_17_54_1","doi-asserted-by":"publisher","DOI":"10.1037\/ccp0000402"},{"key":"e_1_2_17_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2015.05.010"},{"key":"e_1_2_17_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(04)00908\u20101"},{"key":"e_1_2_17_57_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pharmtox\u2010010818\u2010021542"},{"key":"e_1_2_17_58_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1254\u201018.2018"},{"key":"e_1_2_17_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2016.10.001"},{"key":"e_1_2_17_60_1","doi-asserted-by":"publisher","DOI":"10.1037\/h0036128"},{"key":"e_1_2_17_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u201094\u2010009\u20108225\u20103_18"},{"issue":"6","key":"e_1_2_17_62_1","first-page":"12","article-title":"An opponent\u2010process theory of motivation","volume":"68","author":"Solomon RL","year":"1978","journal-title":"Am Econ Rev"},{"key":"e_1_2_17_63_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002280"},{"key":"e_1_2_17_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606\u2010020\u201006251\u2010w"},{"key":"e_1_2_17_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1369\u20101600.2009.00194.x"},{"key":"e_1_2_17_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2019.05.023"},{"key":"e_1_2_17_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526\u20104637.2010.00881.x"},{"key":"e_1_2_17_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2021.12.006"},{"key":"e_1_2_17_69_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542\u2010200603000\u201000025"},{"key":"e_1_2_17_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2020.10.001"},{"key":"e_1_2_17_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcbs.2014.04.003"},{"key":"e_1_2_17_72_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002800"},{"key":"e_1_2_17_73_1","doi-asserted-by":"publisher","DOI":"10.1037\/ser0000099"},{"key":"e_1_2_17_74_1","doi-asserted-by":"publisher","DOI":"10.1086\/508180"},{"key":"e_1_2_17_75_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.1981.tb01189.x"},{"key":"e_1_2_17_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010018\u20100953\u2010z"},{"key":"e_1_2_17_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864\u2010021\u201000910\u20108"},{"key":"e_1_2_17_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2005.05.003"},{"key":"e_1_2_17_79_1","doi-asserted-by":"publisher","DOI":"10.1080\/10550887.2012.759872"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.15972","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T07:56:50Z","timestamp":1732780610000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.15972"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,26]]},"references-count":78,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/bcp.15972"],"URL":"https:\/\/doi.org\/10.1111\/bcp.15972","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,26]]}}}