Editing Celecoxib (section)

==Research==

===Psychiatry===
On the theory that inflammation plays a role in the pathogenesis of major mental disorders, celecoxib has been trialed for a number of psychiatric disorders, including [[major depression]], [[bipolar disorder]], and [[schizophrenia]].<ref name="repurposed2021">{{cite journal | vauthors = Bartoli F, Cavaleri D, Bachi B, Moretti F, Riboldi I, Crocamo C, Carrà G | title = Repurposed drugs as adjunctive treatments for mania and bipolar depression: A meta-review and critical appraisal of meta-analyses of randomized placebo-controlled trials | journal = Journal of Psychiatric Research | date = September 2021 | volume = 143 | pages = 230–238 | doi = 10.1016/j.jpsychires.2021.09.018| pmid = 34509090 | s2cid = 237485915 }}</ref><ref>{{cite journal | vauthors = Müller N, Myint AM, Krause D, Weidinger E, Schwarz MJ | title = Anti-inflammatory treatment in schizophrenia | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 42 | pages = 146–53 | date = April 2013 | pmid = 23178230 | doi = 10.1016/j.pnpbp.2012.11.008 | s2cid = 22078590 }}</ref><ref name=":0">{{cite journal | vauthors = Na KS, Lee KJ, Lee JS, Cho YS, Jung HY | title = Efficacy of adjunctive celecoxib treatment for patients with major depressive disorder: a meta-analysis | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 48 | pages = 79–85 | date = January 2014 | pmid = 24056287 | doi = 10.1016/j.pnpbp.2013.09.006 | s2cid = 35885429 }}</ref><ref>{{cite journal | vauthors = Rosenblat JD, Cha DS, Mansur RB, McIntyre RS | title = Inflamed moods: a review of the interactions between inflammation and mood disorders | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 53 | pages = 23–34 | date = August 2014 | pmid = 24468642 | doi = 10.1016/j.pnpbp.2014.01.013 | s2cid = 32289214 }}</ref><ref>{{cite journal | vauthors = Fond G, Hamdani N, Kapczinski F, Boukouaci W, Drancourt N, Dargel A, Oliveira J, Le Guen E, Marlinge E, Tamouza R, Leboyer M | title = Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review | journal = Acta Psychiatrica Scandinavica | volume = 129 | issue = 3 | pages = 163–79 | date = March 2014 | pmid = 24215721 | doi = 10.1111/acps.12211 | s2cid=23482349 }}</ref>  A 2014 meta-analysis concluded that [[Combination therapy|adjunctive]] treatment with celecoxib improved depressive symptoms, response, and remission rates compared to placebo.<ref name=":0" />

====Bipolar disorder====
A meta-analysis considering trials of celecoxib as an adjunctive treatment in [[bipolar disorder]] was inconclusive citing low evidence quality.<ref name="repurposed2021"/>

===Familial adenomatous polyposis===
It has been used to reduce colon and rectal polyps in people with familial adenomatous polyposis, but it is not known if it decreases rates of [[cancer]],<ref name=AHFS2019/> so it is not a good choice for this reason.<ref name=AHFS2019/>

===Cancer prevention===
The use of celecoxib to reduce the risk of [[colorectal cancer]] has been investigated, but neither celecoxib nor any other drug is indicated for this use.<ref>{{cite journal | vauthors = Rial NS, Zell JA, Cohen AM, Gerner EW | title = Clinical end points for developing pharmaceuticals to manage patients with a sporadic or genetic risk of colorectal cancer | journal = [[Expert Review of Gastroenterology & Hepatology]] | volume = 6 | issue = 4 | pages = 507–17 | date = August 2012 | pmid = 22928902 | pmc = 3587976 | doi = 10.1586/egh.12.23 }}</ref> Small-scale clinical trials in very high-risk people (belonging to [[Familial adenomatous polyposis|FAP]] families) showed celecoxib can prevent polyp growth. Hence, large-scale randomized clinical trials were undertaken.<ref name="Bertagnolli">{{cite journal | vauthors = Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET | title = Celecoxib for the prevention of sporadic colorectal adenomas | journal = The New England Journal of Medicine | volume = 355 | issue = 9 | pages = 873–84 | date = August 2006 | pmid = 16943400 | doi = 10.1056/NEJMoa061355 | doi-access = free }}</ref> Results show a 33 to 45% polyp recurrence reduction in people treated with celecoxib each day. However, serious cardiovascular events were significantly more frequent in the celecoxib-treated groups. Aspirin shows a similar (and possibly larger) protective effect,<ref name="Baron">{{cite journal | vauthors = Baron JA, Cole BF, Sandler RS, Haile RW, Ahnen D, Bresalier R, McKeown-Eyssen G, Summers RW, Rothstein R, Burke CA, Snover DC, Church TR, Allen JI, Beach M, Beck GJ, Bond JH, Byers T, Greenberg ER, Mandel JS, Marcon N, Mott LA, Pearson L, Saibil F, van Stolk RU | title = A randomized trial of aspirin to prevent colorectal adenomas | journal = The New England Journal of Medicine | volume = 348 | issue = 10 | pages = 891–9 | date = March 2003 | pmid = 12621133 | doi = 10.1056/NEJMoa021735 | doi-access = free }}</ref><ref name="Sandler">{{cite journal | vauthors = Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R, Petrelli N, [[James Pipas|Pipas JM]], Karp DD, Loprinzi CL, Steinbach G, Schilsky R | title = A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer | journal = The New England Journal of Medicine | volume = 348 | issue = 10 | pages = 883–90 | date = March 2003 | pmid = 12621132 | doi = 10.1056/NEJMoa021633 | doi-access = free }}</ref><ref name="Bosetti">{{cite journal | vauthors = Bosetti C, Talamini R, Franceschi S, Negri E, Garavello W, La Vecchia C | title = Aspirin use and cancers of the upper aerodigestive tract | journal = British Journal of Cancer | volume = 88 | issue = 5 | pages = 672–4 | date = March 2003 | pmid = 12618872 | pmc = 2376339 | doi = 10.1038/sj.bjc.6600820 }}</ref> has demonstrated cardioprotective effects and is significantly cheaper, but no head-to-head clinical trials have compared the two drugs.

===Cancer treatment===
Different from cancer prevention, cancer treatment is focused on the therapy of tumors that have already formed and have established themselves inside the patient. Many studies are going on to determine whether celecoxib might be useful for this latter condition.<ref name="Dannenberg">{{cite journal | vauthors = Dannenberg AJ, Subbaramaiah K | title = Targeting cyclooxygenase-2 in human neoplasia: rationale and promise | journal = Cancer Cell | volume = 4 | issue = 6 | pages = 431–6 | date = December 2003 | pmid = 14706335 | doi = 10.1016/S1535-6108(03)00310-6 | doi-access = free }}</ref> However, during molecular studies in the laboratory, it became apparent that celecoxib could interact with other intracellular components besides its most famous target, COX-2. The discovery of these additional targets has generated much controversy, and the initial assumption that celecoxib reduces tumor growth primarily by the inhibition of COX-2 became contentious.<ref>{{cite journal | vauthors = Schönthal AH | title = Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy | journal = British Journal of Cancer | volume = 97 | issue = 11 | pages = 1465–8 | date = December 2007 | pmid = 17955049 | pmc = 2360267 | doi = 10.1038/sj.bjc.6604049 }}</ref>

Certainly, the inhibition of COX-2 is paramount for the anti-inflammatory and analgesic function of celecoxib. However, whether inhibition of COX-2 also plays a dominant role in this drug's anticancer effects is unclear. For example, a recent study with [[malignant tumor]] cells showed celecoxib could inhibit the growth of these cells ''[[in vitro]]'', but COX-2 played no role in this outcome; even more strikingly, the anticancer effects of celecoxib were also obtained with the use of cancer cell types that do not even contain COX-2.<ref name="Chuang">{{cite journal | vauthors = Chuang HC, Kardosh A, Gaffney KJ, Petasis NA, Schönthal AH | title = COX-2 inhibition is neither necessary nor sufficient for celecoxib to suppress tumor cell proliferation and focus formation in vitro | journal = Molecular Cancer | volume = 7 | issue = 1 | pages = 38 | date = May 2008 | pmid = 18485224 | pmc = 2396175 | doi = 10.1186/1476-4598-7-38 | doi-access = free }}</ref> [[Karen Seibert]] and colleagues have published research showing antiangiogenic and antitumor activity of celecoxib in animal models.<ref>{{cite journal | vauthors = Masferrer JL, Leahy KM, Koki AT, Zweifel BS, Settle SL, Woerner BM, Edwards DA, Flickinger AG, Moore RJ, Seibert K | title = Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors | journal = Cancer Research | volume = 60 | issue = 5 | pages = 1306–1311 | date = March 2000 | pmid = 10728691 | url = https://aacrjournals.org/cancerres/article/60/5/1306/507043/Antiangiogenic-and-Antitumor-Activities-of }}</ref>

Additional support for the idea that other targets besides COX-2 are important for celecoxib's anticancer effects has come from studies with chemically modified versions of celecoxib. Several dozen [[Analog (chemistry)|analog]]s of celecoxib were generated with small alterations in their [[chemical structure]]s.<ref name="zhu">{{cite journal | vauthors = Zhu J, Song X, Lin HP, Young DC, Yan S, Marquez VE, Chen CS | title = Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents | journal = Journal of the National Cancer Institute | volume = 94 | issue = 23 | pages = 1745–57 | date = December 2002 | pmid = 12464646 | doi = 10.1093/jnci/94.23.1745 | doi-access = free }}</ref> Some of these analogs retained COX-2 inhibitory activity, whereas many others did not. However, when the ability of all these compounds to kill tumor cells in [[cell culture]] was investigated, the antitumor potency did not at all depend on whether or not the respective compound could inhibit COX-2, showing the inhibition of COX-2 was not required for the anticancer effects.<ref name="zhu"/><ref name="Schönthal-analogs">{{cite journal | vauthors = Schönthal AH, Chen TC, Hofman FM, Louie SG, Petasis NA | title = Celecoxib analogs that lack COX-2 inhibitory function: preclinical development of novel anticancer drugs | journal = Expert Opinion on Investigational Drugs | volume = 17 | issue = 2 | pages = 197–208 | date = February 2008 | pmid = 18230053 | doi = 10.1517/13543784.17.2.197 | s2cid = 21093404 }}</ref> One of these compounds, [[2,5-dimethyl-celecoxib]], which entirely lacks the ability to inhibit COX-2, actually displayed stronger anticancer activity than celecoxib.<ref name="Schönthal-antitumor">{{cite journal | vauthors = Schönthal AH | title = Antitumor properties of dimethyl-celecoxib, a derivative of celecoxib that does not inhibit cyclooxygenase-2: implications for glioma therapy | journal = Neurosurgical Focus | volume = 20 | issue = 4 | pages = E21 | date = April 2006 | pmid = 16709027 | doi = 10.3171/foc.2006.20.4.14 | doi-access = free }}</ref>