Editing Naltrexone (section)

==Medical uses==

===Alcohol use disorder===
Naltrexone has been best studied as a treatment for [[alcoholism]].<ref name="pmid27401883">{{cite journal | vauthors = Aboujaoude E, Salame WO | title = Naltrexone: A Pan-Addiction Treatment? | journal = CNS Drugs | volume = 30 | issue = 8 | pages = 719–733 | date = August 2016 | pmid = 27401883 | doi = 10.1007/s40263-016-0373-0 | s2cid = 6372144 }}</ref> Naltrexone has been shown to decrease the quantity and frequency of [[ethanol]] consumption by reducing the dopamine release from the brain after consuming alcohol.<ref name = "Spencer_2023">{{cite journal | vauthors = Spencer CN, Elton A, Dove S, Faulkner ML, Robinson DL, Boettiger CA |date= September 2023 |title=Naltrexone engages a brain reward network in the presence of reward-predictive distractor stimuli in males |journal=Addiction Neuroscience |language=en |volume=7 |pages=100085 |doi=10.1016/j.addicn.2023.100085 |pmid= 37424633 |pmc= 10328541 |s2cid= 257919116 |issn=2772-3925 }}</ref><ref>{{cite journal | vauthors = Spanagel R, Weiss F | title = The dopamine hypothesis of reward: past and current status | journal = Trends in Neurosciences | volume = 22 | issue = 11 | pages = 521–527 | date = November 1999 | pmid = 10529820 | doi = 10.1016/s0166-2236(99)01447-2 | s2cid = 35758115 }}</ref><ref name=Ros2010>{{cite journal | vauthors = Rösner S, Hackl-Herrwerth A, Leucht S, Vecchi S, Srisurapanont M, Soyka M | title = Opioid antagonists for alcohol dependence | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD001867 | date = December 2010 | pmid = 21154349 | doi = 10.1002/14651858.CD001867.pub2 | veditors = Srisurapanont M }}</ref> It does not appear to change the percentage of people drinking.<ref>{{cite journal | vauthors = Donoghue K, Elzerbi C, Saunders R, Whittington C, Pilling S, Drummond C | title = The efficacy of acamprosate and naltrexone in the treatment of alcohol dependence, Europe versus the rest of the world: a meta-analysis | journal = Addiction | volume = 110 | issue = 6 | pages = 920–930 | date = June 2015 | pmid = 25664494 | doi = 10.1111/add.12875 | url = http://findings.org.uk/PHP/dl.php?file=Donoghue_K_1.txt&s=eb | access-date = 15 April 2019 | url-status = live | archive-url = https://web.archive.org/web/20190415034450/https://findings.org.uk/PHP/dl.php?file=Donoghue_K_1.txt&s=eb | archive-date = 15 April 2019 | url-access = subscription }}</ref> Its overall benefit has been described as "modest".<ref>{{cite journal | vauthors = Garbutt JC | title = Efficacy and tolerability of naltrexone in the management of alcohol dependence | journal = Current Pharmaceutical Design | volume = 16 | issue = 19 | pages = 2091–2097 | year = 2010 | pmid = 20482515 | doi = 10.2174/138161210791516459 }}</ref><ref name = "Spencer_2023" /><ref name="Clinical and biological moderators">{{cite journal | vauthors = Garbutt JC, Greenblatt AM, West SL, Morgan LC, Kampov-Polevoy A, Jordan HS, Bobashev GV | title = Clinical and biological moderators of response to naltrexone in alcohol dependence: a systematic review of the evidence | journal = Addiction | volume = 109 | issue = 8 | pages = 1274–1284 | date = August 2014 | pmid = 24661324 | doi = 10.1111/add.12557 }}</ref><ref name="pmid20201811"/>

[[Acamprosate]] may work better than naltrexone for eliminating alcohol abuse, while naltrexone may decrease the desire for [[alcohol (drug)|alcohol]] to a greater extent.<ref name=Mai2013>{{cite journal | vauthors = Maisel NC, Blodgett JC, Wilbourne PL, Humphreys K, Finney JW | title = Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful? | journal = Addiction | volume = 108 | issue = 2 | pages = 275–293 | date = February 2013 | pmid = 23075288 | pmc = 3970823 | doi = 10.1111/j.1360-0443.2012.04054.x }}</ref>

A method pioneered by scientist John David Sinclair (dubbed commercially the “Sinclair Method”) advocates for “pharmacological extinction” of problem drinking behavior by administering naltrexone alongside controlled alcohol consumption. In effect, he argues that naltrexone-induced opioid antagonism sufficiently disrupts reflexive reward mechanisms inherent in the consumption of alcohol and, given enough repetition, will dissociate positive associations formerly made with the consumption of alcohol. A review of eight naltrexone trials concluded, "Although all found benefits from naltrexone with the coping therapy, none of them
found any significant benefit of naltrexone over placebo when combined with support for abstinence."<ref name="Sin2001">{{cite journal |vauthors=Sinclair JD |year=2001 |title=Evidence about the use of naltrexone and for different ways of using it in the treatment of alcoholism |journal=Alcohol and Alcoholism |volume=36 |issue=1 |pages=2–10 |doi=10.1093/alcalc/36.1.2 |pmid=11139409 |doi-access=free}}</ref>

===Opioid use disorder===
Long-acting injectable naltrexone (under the brand name '''Vivitrol''') is an [[opioid antagonist]], blocking the effects of [[heroin]] and other [[Opioid|opioids]], and decreases heroin use compared to a placebo.<ref name=Shar2017>{{cite journal | vauthors = Sharma A, Kelly SM, Mitchell SG, Gryczynski J, O'Grady KE, Schwartz RP | title = Update on Barriers to Pharmacotherapy for Opioid Use Disorders | journal = Current Psychiatry Reports | volume = 19 | issue = 6 | pages = 35 | date = June 2017 | pmid = 28526967 | pmc = 7075636 | doi = 10.1007/s11920-017-0783-9 }}</ref> Unlike [[methadone]] and [[buprenorphine]], it is not a controlled medication.<ref name=Shar2017/> It may decrease cravings for opioids after a number of weeks, and decreases the risk of [[overdose]], at least during the time period that naltrexone is still active, though concern about risk of overdose for those stopping treatment remains.<ref name=AHFS2017/><ref>{{cite journal | vauthors = Sharma B, Bruner A, Barnett G, Fishman M | title = Opioid Use Disorders | journal = Child and Adolescent Psychiatric Clinics of North America | volume = 25 | issue = 3 | pages = 473–487 | date = July 2016 | pmid = 27338968 | pmc = 4920977 | doi = 10.1016/j.chc.2016.03.002 }}</ref><ref name="Wakeman_2020" /> It is given once per month and has better [[Compliance (medicine)|compliance]] and effect for opioid use than the oral formulation.<ref name="ComerSullivan2006">{{cite journal | vauthors = Comer SD, Sullivan MA, Yu E, Rothenberg JL, Kleber HD, Kampman K, Dackis C, O'Brien CP | title = Injectable, sustained-release naltrexone for the treatment of opioid dependence: a randomized, placebo-controlled trial | journal = Archives of General Psychiatry | volume = 63 | issue = 2 | pages = 210–218 | date = February 2006 | pmid = 16461865 | pmc = 4200530 | doi = 10.1001/archpsyc.63.2.210 }}</ref>

A drawback of injectable naltrexone is that it requires patients with opioid use disorder and current physiological dependence to be fully withdrawn before it is initiated to avoid a precipitated [[opioid withdrawal]] that may be quite severe. In contrast, initiation of buprenorphine only requires delay of the first dose until the patient begins to manifest at least mild opioid withdrawal symptoms.<ref name="pmid31062259">{{cite journal | vauthors = Shulman M, Wai JM, Nunes EV | title = Buprenorphine Treatment for Opioid Use Disorder: An Overview | journal = CNS Drugs | volume = 33 | issue = 6 | pages = 567–580 | date = June 2019 | pmid = 31062259 | pmc = 6585403 | doi = 10.1007/s40263-019-00637-z }}</ref> Among patients able to successfully initiate injectable naltrexone, long-term remission rates were similar to those seen in clinical buprenorphine/naloxone administration.<ref name="Comparative effectiveness of extend">{{cite journal | vauthors = Lee JD, Nunes EV, Novo P, Bachrach K, Bailey GL, Bhatt S, Farkas S, Fishman M, Gauthier P, Hodgkins CC, King J, Lindblad R, Liu D, Matthews AG, May J, Peavy KM, Ross S, Salazar D, Schkolnik P, Shmueli-Blumberg D, Stablein D, Subramaniam G, Rotrosen J | title = Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial | journal = Lancet | volume = 391 | issue = 10118 | pages = 309–318 | date = January 2018 | pmid = 29150198 | pmc = 5806119 | doi = 10.1016/S0140-6736(17)32812-X }}</ref> 

The consequence of relapse when weighing the best course of treatment for opiate use disorder remains a concern. Methadone and buprenorphine administration maintain greater [[drug tolerance]] while naltrexone allows tolerance to fade, leading to higher instances of an overdose in people who relapse and thus higher [[Mortality rate|mortality]]. [[World Health Organization]] guidelines state that most patients should be advised to use opioid agonists (e.g., methadone or buprenorphine) rather than opioid antagonists like naltrexone, citing evidence of superiority in reducing mortality and retaining patients in care.<ref>{{cite book |title=Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence |date=2009 |publisher=World Health Organization |isbn=978-92-4-154754-3 |url=https://www.who.int/publications/i/item/9789241547543 |access-date=28 September 2022 |archive-date=28 September 2022 |archive-url=https://web.archive.org/web/20220928174406/https://www.who.int/publications/i/item/9789241547543 |url-status=live }}{{page needed|date=September 2022}}</ref>

A 2011 review found insufficient evidence to determine the effect of naltrexone taken orally on opioid dependence.<ref>{{cite journal | vauthors = Minozzi S, Amato L, Vecchi S, Davoli M, Kirchmayer U, Verster A | title = Oral naltrexone maintenance treatment for opioid dependence | journal = The Cochrane Database of Systematic Reviews | volume = 2011 | issue = 4 | pages = CD001333 | date = April 2011 | pmid = 21491383 | pmc = 7045778 | doi = 10.1002/14651858.CD001333.pub4 | veditors = Minozzi S }}</ref> While some do well with this formulation, it must be taken daily, and a person whose cravings become overwhelming can obtain opioid intoxication simply by skipping a dose. Due to this issue, the usefulness of oral naltrexone in [[opioid use disorder]] is limited by the low retention in treatment. Naltrexone taken orally remains an ideal treatment for a small number of people with opioid use, usually those with a stable social situation and motivation. With additional [[contingency management]] support, naltrexone may be effective in a broader population.<ref>{{cite journal | vauthors = Johansson BA, Berglund M, Lindgren A | title = Efficacy of maintenance treatment with naltrexone for opioid dependence: a meta-analytical review | journal = Addiction | volume = 101 | issue = 4 | pages = 491–503 | date = April 2006 | pmid = 16548929 | doi = 10.1111/j.1360-0443.2006.01369.x }}</ref>

===Others===
Unlike [[varenicline]] (brand name Chantix), naltrexone is not useful for [[smoking cessation|quitting smoking]].<ref>{{cite journal | vauthors = David SP, Lancaster T, Stead LF, Evins AE, Prochaska JJ | title = Opioid antagonists for smoking cessation | journal = The Cochrane Database of Systematic Reviews | volume = 6 | issue = 6 | pages = CD003086 | date = June 2013 | pmid = 23744347 | pmc = 4038652 | doi = 10.1002/14651858.CD003086.pub3 }}</ref> Naltrexone has also been under investigation for reducing [[Behavioral addiction|behavioral addictions]] such as gambling, [[Self-harm|NSSID]] (non-suicidal self-injury disorder), and [[kleptomania]], as well as compulsive sexual behaviors in both offenders and non-offenders (e.g. compulsive porn viewing and masturbation). The results were promising. In one study, the majority of sexual offenders reported a strong reduction in sexual urges and fantasies which reverted to baseline once the medication was discontinued. Case reports have also shown cessation of gambling and other compulsive behaviors, for as long as the medication was taken.<ref>{{cite journal | vauthors = Mouaffak F, Leite C, Hamzaoui S, Benyamina A, Laqueille X, Kebir O | title = Naltrexone in the Treatment of Broadly Defined Behavioral Addictions: A Review and Meta-Analysis of Randomized Controlled Trials | journal = European Addiction Research | volume = 23 | issue = 4 | pages = 204–210 | date = 2017 | pmid = 28877518 | doi = 10.1159/000480539 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ryback RS | title = Naltrexone in the treatment of adolescent sexual offenders | journal = The Journal of Clinical Psychiatry | volume = 65 | issue = 7 | pages = 982–986 | date = July 2004 | pmid = 15291688 | doi = 10.4088/jcp.v65n0715 }}</ref>

When taken at much smaller doses, a regimen known as [[low-dose naltrexone]] (LDN), naltrexone may reduce pain and help to address neurological symptoms. Some patients report that LDN helps reduce their symptoms of [[Chronic fatigue syndrome|ME/CFS]], [[multiple sclerosis]] (MS), [[fibromyalgia]], or autoimmune diseases. Although its mechanism of action is unclear, some have speculated that it may act as an anti-inflammatory.<ref name="Low dose naltrexone - MEpedia">{{cite web | url=https://me-pedia.org/wiki/Low_dose_naltrexone | title=Low dose naltrexone | publisher=MEpedia | access-date=24 September 2022 | archive-date=24 September 2022 | archive-url=https://web.archive.org/web/20220924165641/https://me-pedia.org/wiki/Low_dose_naltrexone | url-status=live }}</ref>  LDN is also being considered as a potential treatment for [[long COVID]].<ref name="Safety and efficacy of low dose nal">{{cite journal | vauthors = O'Kelly B, Vidal L, McHugh T, Woo J, Avramovic G, Lambert JS | title = Safety and efficacy of low dose naltrexone in a long covid cohort; an interventional pre-post study | journal = Brain, Behavior, & Immunity – Health | volume = 24 | pages = 100485 | date = October 2022 | pmid = 35814187 | pmc = 9250701 | doi = 10.1016/j.bbih.2022.100485 }}</ref>

===Available forms===
{{See also|Bupropion/naltrexone|Morphine/naltrexone|Buprenorphine/naltrexone}}

Naltrexone is available and most commonly used in the form of an [[oral administration|oral]] [[tablet (pharmacy)|tablet]] (50&nbsp;mg).<ref name="Milhorn2017" /> Vivitrol, a naltrexone formulation for [[depot injection]] containing 380&nbsp;mg of the medication per vial, is also available.<ref name="Milhorn2017" /><ref name="MedicalNewsToday2006">"{{cite web | url = http://www.medicalnewstoday.com/articles/41707.php | title = Alcoholism Once A Month Injectable Drug, Vivitrol, Approved By FDA | archive-url = https://web.archive.org/web/20090105124047/http://www.medicalnewstoday.com/articles/41707.php | archive-date= 5 January 2009 | work = Medical News Today | date = 16 April 2006 }}</ref> Additionally, naltrexone [[subcutaneous implant]]s that are surgically implanted are available.<ref name=TGA>{{cite web | url = https://www.ebs.tga.gov.au/ebs/ANZTPAR/PublicWeb.nsf/cuMedicines?OpenView | title = Australian Register of Therapeutic Goods Medicines | access-date = 22 March 2009 | author = Therapeutic Goods Administration | format = Online database of approved medicines | url-status = live | archive-url = https://web.archive.org/web/20090514095145/https://www.ebs.tga.gov.au/ebs/ANZTPAR/PublicWeb.nsf/cuMedicines?OpenView | archive-date = 14 May 2009 }}</ref> While these are manufactured in Australia, they are not authorized for use within Australia, but only for export.<ref>{{cite web | url = https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs%2FPublicHTML%2FpdfStore.nsf&docid=12AA89E8C8E53B46CA257FA7004211EE&agid=(PrintDetailsPublic)&actionid=1 | title = Australian Register of Therapeutic Goods Medicines | access-date = 27 April 2017 | author = Therapeutic Goods Administration | format = Online database of approved medicines, specific entry for "O'Neil Long Acting Naltrexone Implant" }} {{Dead link|date=October 2022 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> By 2009, naltrexone implants showed superior efficacy in the treatment of heroin dependence when compared to the oral form.<ref>{{cite journal | vauthors = Hulse GK, Morris N, Arnold-Reed D, Tait RJ | title = Improving clinical outcomes in treating heroin dependence: randomized, controlled trial of oral or implant naltrexone | journal = Archives of General Psychiatry | volume = 66 | issue = 10 | pages = 1108–1115 | date = October 2009 | pmid = 19805701 | doi = 10.1001/archgenpsychiatry.2009.130 | doi-access = free }}</ref>