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A comprehensive systematic review and meta\u2010analysis on current evidence can provide a basis for sound recommendations in clinical practice. A database search for controlled trials on the use of non\u2010opioids in adult palliative patients was performed in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, and EMBASE from inception to 18 February 2018. Endpoints were pain intensity, opioid\u2010sparing effects, safety, and quality of life. Studies with similar patients, interventions, and outcomes were included in the meta\u2010analyses. Our systematic search was able to only identify studies dealing with cancer pain. Of 5991 retrieved studies, 43 could be included (<jats:italic>n<\/jats:italic>\u00a0=\u00a02925 patients). There was no convincing evidence for satisfactory pain relief by acetaminophen alone or in combination with strong opioids. We found substantial evidence of moderate quality for a satisfactory pain relief in cancer by non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs), flupirtine, and dipyrone compared with placebo or other analgesics. There was no evidence for a superiority of one specific non\u2010opioid. There was moderate quality of evidence for a similar pain reduction by NSAIDs in the usual dosage range compared with up to 15\u00a0mg of morphine or opioids of equianalgesic potency. The combination of NSAID and step III opioids showed a beneficial effect, without a decreased tolerability. There is scarce evidence concerning the combination of NSAIDs with weak opioids. There are no randomized\u2010controlled studies on the use of non\u2010opioids in a wide range of end\u2010stage diseases except for cancer. Non\u2010steroidal anti\u2010inflammatory drugs, flupirtine, and dipyrone can be recommended for the treatment of cancer pain either alone or in combination with strong opioids. The use of acetaminophen in the palliative setting cannot be recommended. Studies are not available for long\u2010term use. There is a lack of evidence regarding pain treatment by non\u2010opioids in specific cancer entities.<\/jats:p>","DOI":"10.1002\/jcsm.12352","type":"journal-article","created":{"date-parts":[[2018,10,30]],"date-time":"2018-10-30T04:34:54Z","timestamp":1540874094000},"page":"1235-1254","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Systematic review and meta\u2010analysis on non\u2010opioid analgesics in palliative medicine"],"prefix":"10.1002","volume":"9","author":[{"given":"Robert H.","family":"Sch\u00fcchen","sequence":"first","affiliation":[{"name":"Department of Palliative Medicine University Hospital of Bonn  Bonn Germany"},{"name":"Department of Internal Medicine II DRK\u2010Hospital Neuwied  Neuwied Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"M\u00fccke","sequence":"additional","affiliation":[{"name":"Department of Palliative Medicine University Hospital of Bonn  Bonn Germany"},{"name":"Center for Rare Diseases Bonn (ZSEB) University Hospital of Bonn  Bonn Germany"},{"name":"Department of General Practice and Family Medicine University Hospital of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milka","family":"Marinova","sequence":"additional","affiliation":[{"name":"Department of Radiology University Hospital of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitrij","family":"Kravchenko","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine and Psychotherapy University Hospital of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried","family":"H\u00e4user","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine and Psychotherapy Technische Universit\u00e4t M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Radbruch","sequence":"additional","affiliation":[{"name":"Department of Palliative Medicine University Hospital of Bonn  Bonn Germany"},{"name":"Centre for Palliative Care Malteser Hospital Bonn\/Rhein\u2010Sieg  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupert","family":"Conrad","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine and Psychotherapy University Hospital of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,29]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"The Global Atlas of Palliative Care at the End of Life","author":"Connor S","year":"2014"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.18.2476"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2015.12.340"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0b013e3182a631c5"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.12.2756"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD005180"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD012638"},{"key":"e_1_2_7_9_1","article-title":"Oral paracetamol (acetaminophen) for cancer pain","author":"Wiffen PJ","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S105892"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3111\/13696998.2011.604369"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.4088\/PCC.v10n0502"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2010.03.002"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11136-010-9707-4"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.52.8356"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.suponc.2011.04.002"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60236-5"},{"key":"e_1_2_7_18_1","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [Updated March 2011]","author":"Higgins J","year":"2011"},{"key":"e_1_2_7_19_1","volume-title":"Review Manager (RevMan) [Computer Program]. 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