Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Haloperidol: Difference between pages

{{short description|Typical antipsychotic medication}}

{{Use dmy dates|date=November 2017}}

{{Use American English|date=November 2017}}

{{Drugbox

| Watchedfields = changed

| verifiedrevid = 464369120

| width = 200

| width2 = 200

| pronounce = {{IPAc-en|ˌ|h|æ|l|oʊ|ˈ|p|ɛ|r|ɪ|d|ɒ|l}}

| tradename = Haldol, Serenace, others

| DailyMedID = Haloperidol

| pregnancy_AU = C

| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Haloperidol Use During Pregnancy | website=Drugs.com | date=10 February 2020 | url=https://www.drugs.com/pregnancy/haloperidol.html | access-date=13 September 2020}}</ref>

| pregnancy_US = C

| pregnancy_US_comment = <ref name="Drugs.com pregnancy" />

| legal_AU = S4

| legal_BR = C1

| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>

| legal_CA = Rx-only

| legal_UK = POM

| legal_US = Rx-only

| routes_of_administration = [[Oral administration|By mouth]], [[Intramuscular injection|intramuscular]], [[Intravenous therapy|intravenous]], [[Depot injection|depot]] (as [[decanoate]] [[ester]])

| class = [[Typical antipsychotic]]

| ATC_prefix = N05

| ATC_suffix = AD01

| bioavailability = 60–70% (by mouth)<ref name = PK1999 />

| protein_bound = ~90%<ref name = PK1999 />

| metabolism = Liver-mediated<ref name = PK1999 />

| elimination_half-life = 14–26 hours (IV), 20.7 hours (IM), 14–37 hours (oral)<ref name=PK1999/>

| excretion = [[Bile duct|Biliary]] (hence in feces) and in urine<ref name = PK1999 /><ref name=TGA>{{cite web |title = Product Information Serenace |work = TGA eBusiness Services |publisher = Aspen Pharma Pty Ltd |date = 29 September 2011 |access-date = 29 May 2014 |url = https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-03532-3 |format = PDF |url-status = live |archive-url = https://web.archive.org/web/20170314204106/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-03532-3 |archive-date = 14 March 2017 }}</ref>

| IUPAC_name = 4-[4-(4-Chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butan-1-one

| C=21 | H=23 | Cl=1 | F=1 | N=1 | O=2

<!-- Definition and uses -->

'''Haloperidol''', sold under the brand name '''Haldol''' among others, is a [[typical antipsychotic]] medication.<ref name=AHFS2015 /> Haloperidol is used in the treatment of [[schizophrenia]], tics in [[Tourette syndrome]], [[mania]] in [[bipolar disorder]], [[delirium]], agitation, acute [[psychosis]], and [[hallucinations]] from [[alcohol withdrawal]].<ref name=AHFS2015 /><ref name= NEJM2014>{{cite journal | vauthors = Schuckit MA | title = Recognition and management of withdrawal delirium (delirium tremens) | journal = The New England Journal of Medicine | volume = 371 | issue = 22 | pages = 2109–2113 | date = November 2014 | pmid = 25427113 | doi = 10.1056/NEJMra1407298 | s2cid = 205116954 | url = https://escholarship.org/uc/item/08b9z9th }}</ref><ref>{{cite journal | vauthors = Plosker GL | title = Quetiapine: a pharmacoeconomic review of its use in bipolar disorder | journal = PharmacoEconomics | volume = 30 | issue = 7 | pages = 611–631 | date = July 2012 | pmid = 22559293 | doi = 10.2165/11208500-000000000-00000 }}</ref> It may be used by mouth or injection into a [[intramuscular injection|muscle]] or a [[intravenous|vein]].<ref name=AHFS2015 /> Haloperidol typically works within 30 to 60 minutes.<ref name=AHFS2015 /> A long-acting formulation may be used as an injection every four weeks by people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.<ref name= AHFS2015 />

<!-- Side effects -->Haloperidol may result in a movement disorder known as [[tardive dyskinesia]] which may be permanent.<ref name=AHFS2015 /> [[Neuroleptic malignant syndrome]] and [[Drug-induced QT prolongation|QT interval prolongation]] may occur, the latter particularly with IV administration.<ref name=AHFS2015 /> In older people with psychosis due to [[dementia]] it results in an increased risk of death.<ref name= AHFS2015>{{cite web |title = Haloperidol |url = https://www.drugs.com/monograph/haloperidol.html |publisher = The American Society of Health-System Pharmacists |access-date = 2 January 2015 |url-status = live |archive-url = https://web.archive.org/web/20150102120426/http://www.drugs.com/monograph/haloperidol.html |archive-date = 2015-01-02 }}</ref> When taken during pregnancy it may result in problems in the infant.<ref name=AHFS2015 /><ref name=TGA2015>{{cite web |title = Prescribing medicines in pregnancy database |url = http://www.tga.gov.au/hp/medicines-pregnancy.htm |work = Australian Government |access-date = 2 January 2015 |date = 3 March 2014 |url-status = live |archive-url = https://web.archive.org/web/20140408040902/http://www.tga.gov.au/hp/medicines-pregnancy.htm |archive-date = 8 April 2014 }}</ref> It should not be used by people with [[Parkinson's disease]].<ref name=AHFS2015 />

<!-- History, society and culture -->

Haloperidol was discovered in 1958 by [[Paul Janssen]],<ref>{{cite book | vauthors = Sneader W |title = Drug discovery : a history |date = 2005 |publisher = Wiley |location = Chichester |isbn = 978-0-471-89979-2 |page = 124 |edition = Rev. and updated |url = https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA124 |url-status = live |archive-url = https://web.archive.org/web/20151208072014/https://books.google.ca/books?id=Cb6BOkj9fK4C&pg=PA124 |archive-date = 2015-12-08 }}</ref> prepared as part of a [[structure-activity relationship]] investigation into analogs of [[pethidine]] (meperidine).<ref>{{cite book | vauthors = Ravina E |title = The evolution of drug discovery: from traditional medicines to modern drugs |date = 2011 |publisher = Wiley-VCH |location = Weinheim |isbn = 978-3-527-32669-3 |page = 62 |edition = 1. Aufl. |url = https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA62 |url-status = live |archive-url = https://web.archive.org/web/20151208071857/https://books.google.ca/books?id=iDNy0XxGqT8C&pg=PA62 |archive-date = 2015-12-08 }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> It is the most commonly used typical antipsychotic.<ref name=Ste2004>{{cite book | vauthors = Stevens A |title = Health care needs assessment: the epidemiologically based needs assessment reviews |date = 2004 |publisher = Radcliffe Medical |location = Abingdon |isbn = 978-1-85775-892-4 |page = 202 |edition = 2nd |url = https://books.google.com/books?id=HCLIeMG9WgoC&pg=PA202 |url-status = live |archive-url = https://web.archive.org/web/20151208072515/https://books.google.ca/books?id=HCLIeMG9WgoC&pg=PA202 |archive-date = 2015-12-08 }}</ref> In 2020, it was the 303rd most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title = Haloperidol - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Haloperidol | access-date = 7 October 2022}}</ref>

== Physicochemical properties ==

Haloperidol is a crystalline material with a melting temperature of 150&nbsp;°C.<ref>{{cite journal | vauthors = Shan X, Williams AC, Khutoryanskiy VV | title = Polymer structure and property effects on solid dispersions with haloperidol: Poly(N-vinyl pyrrolidone) and poly(2-oxazolines) studies | journal = International Journal of Pharmaceutics | volume = 590 | pages = 119884 | date = November 2020 | pmid = 32950665 | doi = 10.1016/j.ijpharm.2020.119884 | s2cid = 221826541 | url = https://centaur.reading.ac.uk/93015/1/Manuscript-%20accepted.pdf }}</ref> This drug has very low solubility in water (1.4&nbsp;mg/100&nbsp;mL), but it is soluble in chloroform, benzene, methanol, and acetone. It is also soluble in 0.1&nbsp;M [[hydrochloric acid]] (3&nbsp;mg/mL) with heating.<ref>{{Cite web |title=Sigma data sheet on haloperidol |url=https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/documents/848/112/h1512dat.pdf}}</ref>

== Medical uses ==

Haloperidol is used in the control of the symptoms of:

* Acute [[psychosis]], such as drug-induced psychosis caused by amphetamines, [[ketamine]],<ref>{{cite journal | vauthors = Giannini AJ, Underwood NA, Condon M | title = Acute ketamine intoxication treated by haloperidol: a preliminary study | journal = American Journal of Therapeutics | volume = 7 | issue = 6 | pages = 389–391 | date = November 2000 | pmid = 11304647 | doi = 10.1097/00045391-200007060-00008 }}</ref> and [[phencyclidine]],<ref>{{cite journal | vauthors = Giannini AJ, Eighan MS, Loiselle RH, Giannini MC | title = Comparison of haloperidol and chlorpromazine in the treatment of phencyclidine psychosis | journal = Journal of Clinical Pharmacology | volume = 24 | issue = 4 | pages = 202–204 | date = April 1984 | pmid = 6725621 | doi = 10.1002/j.1552-4604.1984.tb01831.x | s2cid = 42278510 }}</ref> and psychosis associated with high fever or metabolic disease. Some evidence has found haloperidol to worsen psychosis due to psilocybin.<ref>{{cite journal | vauthors = Johnson M, Richards W, Griffiths R | title = Human hallucinogen research: guidelines for safety | journal = Journal of Psychopharmacology | volume = 22 | issue = 6 | pages = 603–620 | date = August 2008 | pmid = 18593734 | pmc = 3056407 | doi = 10.1177/0269881108093587 | publisher = [[SAGE Publications]] }}</ref>

* Adjunctive treatment of alcohol and opioid withdrawal

* Agitation and confusion associated with cerebral [[Sclerosis (medicine)|sclerosis]]

* [[alcohol (drug)|Alcohol]]-induced psychosis

* Hallucinations in [[alcohol withdrawal]]<ref name=NEJM2014 />

* Hyperactive [[delirium]] (to control the agitation component of delirium)

* [[Hyperactivity]], [[aggression]]

* Otherwise uncontrollable, severe behavioral disorders in children and adolescents

* [[Schizophrenia]]<ref name="FDA" />

* Therapeutic trial in [[personality disorders]], such as [[borderline personality disorder]]

* Treatment of intractable [[hiccups]]<ref name="BNF">{{cite book |isbn = 978-0-85711-084-8 |title = British National Formulary (BNF) | author = Joint Formulary Committee |year = 2013 |publisher = Pharmaceutical Press |location = London, England |edition = 65th |pages = [https://archive.org/details/bnf65britishnati0000unse/page/229 229–30] |url = https://archive.org/details/bnf65britishnati0000unse/page/229 }}</ref><ref name = MD />

* Treatment of neurological disorders, including [[tic disorder]]s such as [[Tourette syndrome]], and [[Chorea (disease)|chorea]]

* Treatment of severe nausea and emesis in postoperative and [[palliative care]], especially for palliating adverse effects of [[radiation therapy]] and [[chemotherapy]] in [[oncology]]. Also used as a first line antiemetic for acute [[Cannabinoid Hyperemesis Syndrome]].

* As chemical restraint in acute care psychiatry, mainly for violent and self-harming patients (controversial use but very commonly found in movies).<ref name="pmid15985915" />

Haloperidol was considered indispensable for treating psychiatric emergency situations,<ref name="pmid15985915">{{cite journal | vauthors = Currier GW | title = The controversy over "chemical restraint" in acute care psychiatry | journal = Journal of Psychiatric Practice | volume = 9 | issue = 1 | pages = 59–70 | date = January 2003 | pmid = 15985915 | doi = 10.1097/00131746-200301000-00006 | publisher = [[Lippincott Williams & Wilkins]] | s2cid = 22342074 }}</ref><ref name="pmid3736271">{{cite journal |vauthors=Cavanaugh SV |date=September 1986 |title=Psychiatric emergencies |journal=The Medical Clinics of North America |volume=70 |issue=5 |pages=1185–1202 |doi=10.1016/S0025-7125(16)30919-1 |pmid=3736271}}</ref> although the newer atypical drugs have gained a greater role in a number of situations as outlined in a series of consensus reviews published between 2001 and 2005.<ref name="pmid11500996">{{cite journal | vauthors = Allen MH, Currier GW, Hughes DH, Reyes-Harde M, Docherty JP | title = The Expert Consensus Guideline Series. Treatment of behavioral emergencies | journal = Postgraduate Medicine | issue = Spec No | pages = 1–88; quiz 89–90 | date = May 2001 | pmid = 11500996 }}</ref><ref name="pmid15985913">{{cite journal | vauthors = Allen MH, Currier GW, Hughes DH, Docherty JP, Carpenter D, Ross R | title = Treatment of behavioral emergencies: a summary of the expert consensus guidelines | journal = Journal of Psychiatric Practice | volume = 9 | issue = 1 | pages = 16–38 | date = January 2003 | pmid = 15985913 | doi = 10.1097/00131746-200301000-00004 | s2cid = 29363701 }}</ref><ref name="pmid16319571">{{cite journal | vauthors = Allen MH, Currier GW, Carpenter D, Ross RW, Docherty JP | title = The expert consensus guideline series. Treatment of behavioral emergencies 2005 | journal = Journal of Psychiatric Practice | volume = 11 | issue = Suppl 1 | pages = 5–25 | date = November 2005 | pmid = 16319571 | doi = 10.1097/00131746-200511001-00002 | s2cid = 72366588 }}</ref>

In a 2013 comparison of 15 antipsychotics in schizophrenia, haloperidol demonstrated standard effectiveness. It was 13–16% more effective than [[ziprasidone]], [[chlorpromazine]], and [[asenapine]], approximately as effective as [[quetiapine]] and [[aripiprazole]], and 10% less effective than [[paliperidone]].<ref name=pmid23810019>{{cite journal | vauthors = Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM | display-authors = 6 | title = Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis | journal = Lancet | volume = 382 | issue = 9896 | pages = 951–962 | date = September 2013 | pmid = 23810019 | doi = 10.1016/S0140-6736(13)60733-3 | s2cid = 32085212 }}</ref> A 2013 [[systematic review]] compared haloperidol to [[placebo]] in schizophrenia:<ref name=Ada2013>{{cite journal | vauthors = Adams CE, Bergman H, Irving CB, Lawrie S | title = Haloperidol versus placebo for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 11 | issue = 11 | pages = CD003082 | date = November 2013 | pmid = 24242360 | doi = 10.1002/14651858.CD003082.pub3 | url = http://www.cochrane.org/CD003082/SCHIZ_haloperidol-versus-placebo-for-schizophrenia | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20170820120020/http://www.cochrane.org/CD003082/SCHIZ_haloperidol-versus-placebo-for-schizophrenia | archive-date = 2017-08-20 }}</ref>

{| class="wikitable"

! Summary

|-

|Haloperidol often causes troublesome adverse effects. If there is no other antipsychotic drug, using haloperidol to offset the consequences of untreated schizophrenia is justified. Where a choice of drug is available, however, an alternative [[antipsychotic]] with less likelihood of adverse effects such as parkinsonism, [[akathisia]] and acute [[dystonias]] may be more desirable.<ref name=Ada2013 />

|-

| style="padding:0;" |

{| class="wikitable collapsible collapsed" style="width:100%;"

|-

! scope="col" style="text-align: left;"| Outcome

! scope="col" style="text-align: left;"| Findings in words

! scope="col" style="text-align: left;"| Findings in numbers

! scope="col" style="text-align: left;"| Quality of evidence

|-

! colspan="4" style="text-align: left;"| General outcomes

|-

| No marked global improvement<br />Follow-up: >6–24 weeks || Haloperidol, when compared with placebo, reduces the chance of experiencing 'no improvement'. Data are based on moderate quality evidence.

|| [[Relative risk|RR]] 0.67 (0.58 to 0.78) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Moderate]]

|-

| Not discharged from hospital<br />Follow-up: > 6–24 weeks || Haloperidol may reduce the chance of staying in hospital, but, at present it is not possible to be confident about the difference between people receiving haloperidol and people taking placebo. Data supporting this finding are very limited.

|| [[Relative risk|RR]] 0.85 (0.47 to 1.52) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Very low]]

|-

| Relapse<br />Follow-up: < 52 weeks || Haloperidol may reduce the chance of relapse, but, at present there is only very limited data supporting this finding.

|| [[Relative risk|RR]] 0.69 (0.55 to 0.86) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Very low]]

|-

! colspan="4" style="text-align: left;"| Leaving the study early

|-

| Follow-up: > 6–24 weeks || Haloperidol probably slightly reduces the risk of loss to follow up, but the difference between the two treatments is not quite clear. Data supporting this finding are based on moderate quality evidence.

|| [[Relative risk|RR]] 0.54 (0.29 to 1) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Moderate]]

|-

! colspan="4" style="text-align: left;"| [[Adverse event|Adverse effects]] – movement disorders

|-

| Parkinsonism<br />Follow-up: 3 weeks to 3 months || Haloperidol substantially increases the risk of movement disorders. Data are based on moderate quality evidence.

|| [[Relative risk|RR]] 5.48 (2.68 to 11.22) || [[The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach|Moderate]]

|-

! colspan="4" style="text-align: left;"| Missing outcomes

|-

| || Severe adverse events, such as death, and outcomes such as [[Patient satisfaction|satisfaction with treatment]] were not measured/reported in the included studies. || ||

|-

|}

|}

=== Pregnancy and lactation ===

Data from [[Animal testing|animal experiments]] indicate haloperidol is not [[teratogenic]], but is [[embryotoxic]] in high doses. In humans, no controlled studies exist. Reports in pregnant women revealed possible damage to the fetus, although most of the women were exposed to multiple drugs during pregnancy. In addition, reports indicate [[neonates]] exposed to antipsychotic drugs are at risk for [[Extrapyramidal symptoms|extrapyramidal]] and/or withdrawal symptoms following delivery, such as agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder. Following accepted general principles, haloperidol should be given during pregnancy only if the benefit to the mother clearly outweighs the potential fetal risk.<ref name="FDA">{{cite web |url = https://www.drugs.com/pro/haldol.html |title = Haldol Official FDA information, side effects and uses |publisher = Drugs.com |access-date = 2013-10-03 |url-status = live |archive-url = https://web.archive.org/web/20131005001049/http://www.drugs.com/pro/haldol.html |archive-date = 2013-10-05 }}</ref>

Haloperidol is excreted in breast milk. A few studies have examined the impact of haloperidol exposure on breastfed infants and in most cases, there were no adverse effects on infant growth and development.<ref>{{Cite web|url=http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+lactmed:@term+@DOCNO+132|title=LACTMED: Haloperidol|date=31 October 2018|access-date=18 January 2019}}</ref>

=== Other considerations ===

[[File:Haloperidol decanoate highlighting ester group.svg|thumb|right|[[Skeletal formula]] of [[haloperidol decanoate]]. The decanoate group is highlighted in {{color|red|red}}.]]

During long-term treatment of chronic psychiatric disorders, the daily dose should be reduced to the lowest level needed for maintenance of remission. Sometimes, it may be indicated to terminate haloperidol treatment gradually.{{citation needed|date=April 2022}} In addition, during long-term use, routine monitoring including measurement of BMI, blood pressure, fasting blood sugar, and lipids, is recommended due to the risk of side effects.<ref name="APA schizophrenia guideline" />

Other forms of therapy (psychotherapy, occupational therapy/ergotherapy, or social rehabilitation) should be instituted properly.{{Citation needed|date=April 2013}}

PET imaging studies have suggested low doses are preferable. Clinical response was associated with at least 65% occupancy of D2 receptors, while greater than 72% was likely to cause hyperprolactinaemia and over 78% associated with extrapyramidal side effects. Doses of haloperidol greater than 5&nbsp;mg increased the risk of side effects without improving efficacy.<ref>{{cite journal | vauthors = Oosthuizen P, Emsley RA, Turner J, Keyter N | title = Determining the optimal dose of haloperidol in first-episode psychosis | journal = Journal of Psychopharmacology | volume = 15 | issue = 4 | pages = 251–255 | date = December 2001 | pmid = 11769818 | doi = 10.1177/026988110101500403 | s2cid = 40788955 }}</ref> Patients responded with doses under even 2&nbsp;mg in first-episode psychosis.<ref>{{cite journal | vauthors = Tauscher J, Kapur S | title = Choosing the right dose of antipsychotics in schizophrenia: lessons from neuroimaging studies | journal = CNS Drugs | volume = 15 | issue = 9 | pages = 671–678 | year = 2001 | pmid = 11580306 | doi = 10.2165/00023210-200115090-00001 | s2cid = 30091494 }}</ref> For maintenance treatment of schizophrenia, an international consensus conference recommended a reduction dosage by about 20% every 6 months until a minimal maintenance dose is established.<ref name="APA schizophrenia guideline">{{cite web | author = Work Group on Schizophrenia |title = Practice Guideline for the Treatment of Patients With Schizophrenia | edition = Second |url = http://psychiatryonline.org/content.aspx?bookID=28&sectionID=1665359#45892 |archive-url = https://web.archive.org/web/20120327230029/http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1665359#45892 |url-status = dead |archive-date = 27 March 2012 |access-date = 21 April 2014 }}</ref>

* Depot forms are also available; these are injected deeply intramuscularly at regular intervals. The depot forms are not suitable for initial treatment, but are suitable for patients who have demonstrated inconsistency with oral dosages.{{Citation needed|date=April 2013}}

The [[decanoate]] ester of haloperidol ([[haloperidol decanoate]], trade names Haldol decanoate, Halomonth, Neoperidole) has a much longer [[duration of action]], so is often used in people known to be noncompliant with oral medication. A dose is given by intramuscular injection once every two to four weeks.<ref>Goodman and Gilman's ''Pharmacological Basis of Therapeutics'', 10th edition (McGraw-Hill, 2001).{{page needed|date=September 2012}}</ref> The [[IUPAC name]] of haloperidol decanoate is [4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl] decanoate.

[[Topical medication|Topical formulations]] of haloperidol should not be used as treatment for nausea because research does not indicate this therapy is more effective than alternatives.<ref name="AAHPMfive">{{Cite journal |author1 = American Academy of Hospice and Palliative Medicine |author1-link = American Academy of Hospice and Palliative Medicine |title = Five Things Physicians and Patients Should Question |publisher = [[American Academy of Hospice and Palliative Medicine]] |journal = Choosing Wisely: An Initiative of the ABIM Foundation |url = http://www.choosingwisely.org/doctor-patient-lists/american-academy-of-hospice-palliative-medicine/ |access-date = 1 August 2013 |url-status = live |archive-url = https://web.archive.org/web/20130901101934/http://www.choosingwisely.org/doctor-patient-lists/american-academy-of-hospice-palliative-medicine/ |archive-date = 1 September 2013 }}, which cites

* {{cite journal | vauthors = Smith TJ, Ritter JK, Poklis JL, Fletcher D, Coyne PJ, Dodson P, Parker G | title = ABH gel is not absorbed from the skin of normal volunteers | journal = Journal of Pain and Symptom Management | volume = 43 | issue = 5 | pages = 961–966 | date = May 2012 | pmid = 22560361 | doi = 10.1016/j.jpainsymman.2011.05.017 | doi-access = free }}

* {{cite journal | vauthors = Weschules DJ | title = Tolerability of the compound ABHR in hospice patients | journal = Journal of Palliative Medicine | volume = 8 | issue = 6 | pages = 1135–1143 | date = December 2005 | pmid = 16351526 | doi = 10.1089/jpm.2005.8.1135 }}</ref>

== Adverse effects ==

Sources for the following lists of adverse effects:<ref>Product Information [Internet]. 2011 [cited 2013 Sep 29]. Available from: {{cite web |url = https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-03532-3 |title = TGA eBS - Product and Consumer Medicine Information Licence |access-date = 2014-05-29 |url-status = live |archive-url = https://web.archive.org/web/20170314204106/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-03532-3 |archive-date = 2017-03-14 }}</ref><ref>HALDOL® Injection For Intramuscular Injection Only Product Information [Internet]. Janssen; 2011 [cited 2013 Sep 29]. Available from: {{cite web |url = https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-00998-3 |title = TGA eBS - Product and Consumer Medicine Information Licence |access-date = 2013-09-29 |url-status = live |archive-url = https://web.archive.org/web/20170314204054/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-00998-3 |archive-date = 2017-03-14 }}</ref><ref>Truven Health Analytics, Inc. DrugPoint® System (Internet) [cited 2013 Sep 29]. Greenwood Village, CO: Thomsen Healthcare; 2013.</ref><ref>Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.</ref>

As haloperidol is a high-potency typical antipsychotic, it tends to produce significant [[extrapyramidal side effects]]. According to a 2013 meta-analysis of the comparative efficacy and tolerability of 15 antipsychotic drugs it was the most prone of the 15 for causing extrapyramidal side effects.<ref name=pmid23810019/>

With more than 6 months of use 14 percent of users gain weight.<ref>{{cite web | author = FDA Psychopharmacological Drugs Advisory Committee | date = 9 July 2000 |url = https://www.fda.gov/ohrms/dockets/ac/00/backgrd/3619b1a.pdf |title = Briefing Document for ZELDOX CAPSULES (Ziprasidone HCl) |website = [[Food and Drug Administration]] |access-date = 2016-09-30 |url-status = dead |archive-url = https://web.archive.org/web/20170119063641/https://www.fda.gov/ohrms/dockets/ac/00/backgrd/3619b1a.pdf |archive-date = 2017-01-19 }}</ref> Haloperidol may be neurotoxic.<ref name=Neurotoxic>{{cite journal | vauthors = Nasrallah HA, Chen AT | title = Multiple neurotoxic effects of haloperidol resulting in neuronal death | journal = Annals of Clinical Psychiatry | volume = 29 | issue = 3 | pages = 195–202 | date = August 2017 | pmid = 28738100 }}</ref>

'''Common (>1% incidence)'''

* Extrapyramidal side effects including:

** [[Akathisia]] (motor restlessness)

** [[Dystonia]] (continuous spasms and muscle contractions)

** Muscle rigidity

** [[Parkinsonism]] (characteristic symptoms such as rigidity)

* Hypotension

* Anticholinergic side effects such as: (These adverse effects are less common than with lower-potency typical antipsychotics, such as chlorpromazine and thioridazine.)

** Blurred vision

** Constipation

** Dry mouth

* [[Somnolence]] (which is not a particularly prominent side effect, as is supported by the results of the aforementioned meta-analysis.<ref name=pmid23810019/>)

'''Unknown frequency'''

* [[Anemia]]

* [[Headache]]

* Increased respiratory rate

* [[Orthostatic hypotension]]

* [[Prolonged QT interval]]

* Visual disturbances

'''Rare (<1% incidence)'''

{{div col|colwidth=18em}}

* [[Acute hepatic failure]]

* Agitation

* [[Agranulocytosis]]

* [[Anaphylactic reaction]]

* Anorexia

* Bronchospasm

* Cataracts

* [[Cholestasis]]

* Confusional state

* Depression

* Dermatitis exfoliative

* [[Dyspnea]]

* Edema

* [[Extrasystole]]s

* Face edema

* [[Gynecomastia]]

* [[Hepatitis]]

* Hyperglycemia

* Hypersensitivity

* Hyperthermia

* Hypoglycemia

* [[Hyponatremia]]

* Hypothermia

* Increased sweating

* Injection site abscess

* Insomnia

* Itchiness

* Jaundice

* Laryngeal edema

* [[Laryngospasm]]

* [[Leukocytoclastic vasculitis]]

* [[Leukopenia]]

* Liver function test abnormal

* Nausea

* [[Neuroleptic malignant syndrome]]

* [[Neutropenia]]

* [[Pancytopenia]]

* Photosensitivity reaction

* [[Priapism]]

* [[Psychosis|Psychotic disorder]]

* Pulmonary embolism

* Rash

* [[Retinopathy]]

* [[Non-epileptic seizure|Seizure]]

* Sudden death

* [[Tardive dyskinesia]]

* [[Thrombocytopenia]]

* [[Torsades de pointes]]

* Urinary retention

* [[Urticaria]]

* [[Ventricular fibrillation]]

* [[Ventricular tachycardia]]

* Vomiting

{{div col end}}

=== Contraindications ===

* Pre-existing [[coma]], acute stroke

* Severe intoxication with alcohol or other central depressant drugs

* Known allergy against haloperidol or other butyrophenones or other drug ingredients

* Known heart disease, when combined will tend towards cardiac arrest{{Citation needed|date=April 2013}}

=== Special cautions ===

* A multiple-year study suggested this drug and other neuroleptic antipsychotic drugs commonly given to people with Alzheimer's with mild behavioral problems often make their condition worse and its withdrawal was even beneficial for some cognitive and functional measures.<ref>{{cite journal | vauthors = Ballard C, Lana MM, Theodoulou M, Douglas S, McShane R, Jacoby R, Kossakowski K, Yu LM, Juszczak E | display-authors = 6 | title = A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial) | journal = PLOS Medicine | volume = 5 | issue = 4 | pages = e76 | date = April 2008 | pmid = 18384230 | pmc = 2276521 | doi = 10.1371/journal.pmed.0050076 | veditors = Brayne C | quote = Neuroleptics provided no benefit for patients with mild behavioural problems, but were associated with a marked deterioration in verbal skills | doi-access = free }}</ref> <ref name="BBC NEWS 2008">{{cite web | title=Medication 'worsens Alzheimer's' | website=BBC NEWS | date=April 1, 2008 | url=http://news.bbc.co.uk/1/hi/health/7319393.stm | access-date=August 3, 2016}}</ref>

* Elderly patients with dementia-related psychosis: analysis of 17 trials showed the risk of death in this group of patients was 1.6 to 1.7 times that of placebo-treated patients. Most of the causes of death were either cardiovascular or infectious in nature. It is not clear to what extent this observation is attributed to antipsychotic drugs rather than the characteristics of the patients. The drug bears a [[boxed warning]] about this risk.<ref name=FDA />

* Impaired [[liver]] function, as haloperidol is metabolized and eliminated mainly by the liver

* In patients with hyperthyroidism, the action of haloperidol is intensified and side effects are more likely.

* IV injections: risk of hypotension or orthostatic collapse

* Patients at special risk for the development of [[Long QT syndrome|QT prolongation]] ([[hypokalemia]], concomitant use of other drugs causing QT prolongation)

* Patients with a history of leukopenia: a [[complete blood count]] should be monitored frequently during the first few months of therapy and discontinuation of the drug should be considered at the first sign of a clinically significant decline in white blood cells.<ref name=FDA />

* Pre-existing [[Parkinson's disease]]<ref>{{cite journal | vauthors = Leentjens AF, van der Mast RC | title = Delirium in elderly people: an update | journal = Current Opinion in Psychiatry | volume = 18 | issue = 3 | pages = 325–330 | date = May 2005 | pmid = 16639157 | doi = 10.1097/01.yco.0000165603.36671.97 | s2cid = 24709695 }}</ref> or [[dementia with Lewy bodies]]

=== Interactions ===

* [[Amiodarone]]: Q-Tc interval prolongation (potentially dangerous change in heart rhythm).<ref>{{cite journal | vauthors = Bush SE, Hatton RC, Winterstein AG, Thomson MR, Woo GW | title = Effects of concomitant amiodarone and haloperidol on Q-Tc interval prolongation | journal = American Journal of Health-System Pharmacy | volume = 65 | issue = 23 | pages = 2232–2236 | date = December 2008 | pmid = 19020191 | doi = 10.2146/ajhp080039 }}</ref>

* [[Amphetamine]] and [[methylphenidate]]: counteracts increased action of norepinephrine and dopamine in patients with [[narcolepsy]] or [[Attention deficit disorder|ADD]]/[[ADHD]]

* [[Epinephrine]]: action antagonized, paradoxical decrease in blood pressure may result

* [[Guanethidine]]: antihypertensive action antagonized

* [[Levodopa]]: decreased action of levodopa

* [[Lithium (medication)|Lithium]]: rare cases of the following symptoms have been noted: [[encephalopathy]], early and late extrapyramidal side effects, other neurologic symptoms, and coma.<ref>{{cite journal | vauthors = Sandyk R, Hurwitz MD | title = Toxic irreversible encephalopathy induced by lithium carbonate and haloperidol. A report of 2 cases | journal = South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde | volume = 64 | issue = 22 | pages = 875–876 | date = November 1983 | pmid = 6415823 }}</ref>

* [[Methyldopa]]: increased risk of extrapyramidal side effects and other unwanted central effects

* Other central depressants (alcohol, tranquilizers, narcotics): actions and side effects of these drugs (sedation, respiratory depression) are increased. In particular, the doses of concomitantly used opioids for chronic pain can be reduced by 50%.

* Other drugs metabolized by the CYP3A4 enzyme system: inducers such as [[carbamazepine]], [[phenobarbital]], and [[rifampicin]] decrease plasma levels and inhibitors such as [[quinidine]], [[buspirone]], and [[fluoxetine]] increase plasma levels<ref name=FDA />

* [[Tricyclic antidepressants]]: metabolism and elimination of tricyclics significantly decreased, increased toxicity noted (anticholinergic and cardiovascular side effects, lowering of seizure threshold)

=== Potential neurotoxicity ===

Several lines of evidence suggest that haloperidol exhibits neurotoxicity.<ref name="pmid28738100">{{cite journal | vauthors = Nasrallah HA, Chen AT | title = Multiple neurotoxic effects of haloperidol resulting in neuronal death | journal = Annals of Clinical Psychiatry | volume = 29 | issue = 3 | pages = 195–202 | date = August 2017 | pmid = 28738100 | doi = }}</ref><ref>{{cite journal | vauthors = Pierre JM | title = Time to retire haloperidol? | journal = Current Psychiatry | volume = 19 | issue = 5 | page = 19 | url = https://www.mdedge.com/psychiatry/article/221293/schizophrenia-other-psychotic-disorders }}</ref> Some studies report an association between antipsychotic medications, especially first-generation agents, and a decline in gray matter volume.<ref>Id.</ref> Haloperidol may exert deleterious effects on the dorsolateral prefrontal cortex (DLPFC) by attenuating [[Brain-derived neurotrophic factor|BDNF]] transcription and expression, associated with an increase in the long non-coding RNA BDNF-AS in the DLPFC.<ref name="pmid36816400">{{cite journal | vauthors = Hemby SE, McIntosh S | title = Chronic haloperidol administration downregulates select BDNF transcript and protein levels in the dorsolateral prefrontal cortex of rhesus monkeys | journal = Frontiers in Psychiatry | volume = 14 | issue = | pages = 1054506 | date = 2023 | pmid = 36816400 | pmc = 9932326 | doi = 10.3389/fpsyt.2023.1054506 | doi-access = free }}</ref>

===Discontinuation===

The [[British National Formulary]] recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.<ref name="Group 2009 192">{{cite book |editor1-first=BMJ | editor = Joint Formulary Committee | title = British National Formulary | edition = 57 | date = March 2009 |publisher=Royal Pharmaceutical Society of Great Britain |location=United Kingdom |isbn=978-0-85369-845-6 |page=192 |chapter=4.2.1 |quote=Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.}}</ref> Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.<ref name=Had2004>{{cite book | vauthors = Haddad PM, Dursun S, Deakin B |title=Adverse Syndromes and Psychiatric Drugs: A Clinical Guide |date=2004 |publisher=OUP Oxford |isbn=9780198527480 |pages=207–216 |url=https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207 |language=en}}</ref> Other symptoms may include restlessness, increased sweating, and trouble sleeping.<ref name=Had2004/> Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.<ref name=Had2004/> Symptoms generally resolve after a short period of time.<ref name=Had2004/>

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.<ref>{{cite journal | vauthors = Moncrieff J | title = Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse | journal = Acta Psychiatrica Scandinavica | volume = 114 | issue = 1 | pages = 3–13 | date = July 2006 | pmid = 16774655 | doi = 10.1111/j.1600-0447.2006.00787.x | s2cid = 6267180 }}</ref> It may also result in reoccurrence of the condition that is being treated.<ref>{{cite book | vauthors = Sacchetti E, Vita A, Siracusano A, Fleischhacker W |title=Adherence to Antipsychotics in Schizophrenia |date=2013 |publisher=Springer Science & Business Media |isbn=9788847026797 |page=85 |url=https://books.google.com/books?id=odE-AgAAQBAJ&pg=PA85 |language=en}}</ref> Rarely tardive dyskinesia can occur when the medication is stopped.<ref name=Had2004/>

== Overdose ==

=== Symptoms ===

Symptoms are usually due to side effects. Most often encountered are:

* [[Anticholinergic]] side effects (dry mouth, constipation, paralytic [[ileus]], difficulties in urinating, decreased [[perspiration]])

* Coma in severe cases, accompanied by respiratory depression and massive hypotension, shock

* [[Hypotension]] or [[hypertension]]

* Rarely, serious ventricular arrhythmia (''torsades de pointes''), with or without prolonged [[QT-time]]

* [[Sedation]]

* Severe [[extrapyramidal symptoms|extrapyramidal]] side effects with muscle rigidity and tremors, [[akathisia]], etc.

=== Treatment ===

Treatment is mostly symptomatic and involves intensive care with stabilization of vital functions. In early detected cases of oral overdose, induction of [[emesis]], [[gastric lavage]], and the use of [[activated charcoal]] can be tried. In the case of a severe overdose, antidotes such as [[bromocriptine]] or [[ropinirole]] may be used to treat the extrapyramidal effects caused by haloperidol, acting as dopamine receptor agonists.{{Citation needed|date=April 2013}} ECG and vital signs should be monitored especially for QT prolongation and severe arrhythmias should be treated with antiarrhythmic measures.<ref name=FDA />

=== Prognosis ===

An overdose of haloperidol can be fatal,<ref>{{cite web |url = https://www.drugs.com/mtm/haloperidol.html |title = Haloperidol at Drugs.com |url-status = live |archive-url = https://web.archive.org/web/20111122170902/http://www.drugs.com/mtm/haloperidol.html |archive-date = 2011-11-22 }}</ref> but in general the prognosis after overdose is good, provided the person has survived the initial phase.

== Pharmacology ==

[[File:Haloperidol 10 MG Oral Tablet.jpg|thumb|Haloperidol, 10-mg oral tablet]]

Haloperidol is a typical [[butyrophenone]]-type antipsychotic that exhibits high-affinity dopamine D₂ receptor antagonism and slow receptor dissociation kinetics.<ref>{{cite journal | vauthors = Seeman P, Tallerico T | title = Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors | journal = Molecular Psychiatry | volume = 3 | issue = 2 | pages = 123–134 | date = March 1998 | pmid = 9577836 | doi = 10.1038/sj.mp.4000336 | doi-access = free }}</ref> It has [[pharmacology|effects]] similar to the [[phenothiazine]]s.<ref name = MD>{{cite web |title = Haloperidol |work = Martindale: The Complete Drug Reference |publisher = Pharmaceutical Press |date = 13 December 2013 |access-date = 29 May 2014 |url = http://www.medicinescomplete.com/mc/martindale/current/ms-18332-f.htm |editor = Brayfield, A |location = London, UK }}</ref> The drug binds preferentially to D₂ and α₁ receptors at low dose (ED₅₀ = 0.13 and 0.42&nbsp;mg/kg, respectively), and 5-HT₂ receptors at a higher dose (ED₅₀ = 2.6&nbsp;mg/kg). Given that antagonism of D₂ receptors is more beneficial on the positive symptoms of schizophrenia and antagonism of 5-HT₂ receptors on the negative symptoms, this characteristic underlies haloperidol's greater effect on delusions, hallucinations and other manifestations of psychosis.<ref>{{cite journal | vauthors = Schotte A, Janssen PF, Megens AA, Leysen JE | title = Occupancy of central neurotransmitter receptors by risperidone, clozapine and haloperidol, measured ex vivo by quantitative autoradiography | journal = Brain Research | volume = 631 | issue = 2 | pages = 191–202 | date = December 1993 | pmid = 7510574 | doi = 10.1016/0006-8993(93)91535-z | s2cid = 34455982 }}</ref> Haloperidol's negligible affinity for histamine H₁ receptors and muscarinic M₁ acetylcholine receptors yields an antipsychotic with a lower incidence of sedation, weight gain, and [[orthostatic hypotension]] though having higher rates of treatment emergent [[extrapyramidal symptom]]s.

{| class="wikitable"

|+ Haloperidol binding profile

! Receptor !! Action !! [[Ligand (biochemistry)|K_i]] (nM)

|-

|[[Dopamine receptor D1|D₁]]

|[[silent antagonist]]

|Unknown efficiency {{Citation needed|date=April 2013}}

|-

|[[Dopamine receptor D5|D₅]]

|silent antagonist

|Unknown efficiency{{Citation needed|date=April 2013}}

|-

|[[Dopamine receptor D2|D₂]]

|[[inverse agonist]]

|0.7<ref>{{cite journal | vauthors = Leysen JE, Janssen PM, Gommeren W, Wynants J, Pauwels PJ, Janssen PA | title = In vitro and in vivo receptor binding and effects on monoamine turnover in rat brain regions of the novel antipsychotics risperidone and ocaperidone | journal = Molecular Pharmacology | volume = 41 | issue = 3 | pages = 494–508 | date = March 1992 | pmid = 1372084 | url = http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1372084 }}</ref>

|-

|[[Dopamine receptor D3|D₃]]

|inverse agonist

|0.2<ref>{{cite journal | vauthors = Mohell N | title = Agonist and inverse agonist activity at the dopamine D3 receptor measured by guanosine 5'--gamma-thio-triphosphate--35S- binding | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 285 | issue = 1 | pages = 119–126 | date = April 1998 | pmid = 9536001 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9536001 }}</ref>

|-

|[[Dopamine receptor D4|D₄]]

|inverse agonist

|5–9<ref>{{cite journal | vauthors = Leysen JE, Janssen PM, Megens AA, Schotte A | title = Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity | journal = The Journal of Clinical Psychiatry | volume = 55 Suppl | issue = Suppl | pages = 5–12 | date = May 1994 | pmid = 7520908 }}</ref>

|-

|[[Sigma-1 receptor|σ₁]]

|(irreversible inactivation by haloperidol metabolite HPP⁺)

|3<ref>{{cite journal | vauthors = Cobos EJ, del Pozo E, Baeyens JM | title = Irreversible blockade of sigma-1 receptors by haloperidol and its metabolites in guinea pig brain and SH-SY5Y human neuroblastoma cells | journal = Journal of Neurochemistry | volume = 102 | issue = 3 | pages = 812–825 | date = August 2007 | pmid = 17419803 | doi = 10.1111/j.1471-4159.2007.04533.x | s2cid = 24130758 }}</ref>

|-

|[[Sigma-2 receptor|σ₂]]

|agonist

|54<ref>{{cite journal | vauthors = Colabufo NA, Berardi F, Contino M, Niso M, Abate C, Perrone R, Tortorella V | title = Antiproliferative and cytotoxic effects of some sigma2 agonists and sigma1 antagonists in tumour cell lines | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 370 | issue = 2 | pages = 106–113 | date = August 2004 | pmid = 15322732 | doi = 10.1007/s00210-004-0961-2 | s2cid = 24971006 }}</ref>

|-

|[[5-HT1A receptor|5-HT_1A]]

|agonist

|1,927<ref name="affindata">{{cite journal | vauthors = Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, Jayathilake K, Meltzer HY, Roth BL | display-authors = 6 | title = H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs | journal = Neuropsychopharmacology | volume = 28 | issue = 3 | pages = 519–526 | date = March 2003 | pmid = 12629531 | doi = 10.1038/sj.npp.1300027 | author8-link = Herbert Y. Meltzer | doi-access = free | author9-link = Bryan Roth }}</ref>

|-

|[[5-HT2A receptor|5-HT_2A]]

|silent antagonist

|53<ref name="affindata" />

|-

|[[5-HT2C receptor|5-HT_2C]]

|silent antagonist

|10,000<ref name="affindata" />

|-

|[[5-HT6 receptor|5-HT₆]]

|silent antagonist

|3,666<ref name="affindata" />

|-

|[[5-HT7 receptor|5-HT₇]]

|[[irreversible antagonist|irreversible silent antagonist]]

|377.2<ref name="affindata" />

|-

|[[Histamine H1 receptor|H₁]]

|silent antagonist

|1,800<ref name="affindata" />

|-

|[[Muscarinic acetylcholine receptor M1|M₁]]

|silent antagonist

|10,000<ref name="affindata" />

|-

|[[Alpha-1A adrenergic receptor|α_1A]]

|silent antagonist

|12<ref name="affindata" />

|-

|[[Alpha-2A adrenergic receptor|α_2A]]

|silent antagonist

|1,130<ref name="affindata" />

|-

|[[Alpha-2B adrenergic receptor|α_2B]]

|silent antagonist

|480<ref name="affindata" />

|-

|[[Alpha-2C adrenergic receptor|α_2C]]

|silent antagonist

|550<ref name="affindata" />

|-

|NR1/NR2B subunit containing [[NMDA receptor]]

|antagonist; [[ifenprodil]] site

|[[IC50|IC₅₀]] – 2,000<ref>{{cite journal | vauthors = Ilyin VI, Whittemore ER, Guastella J, Weber E, Woodward RM | title = Subtype-selective inhibition of N-methyl-D-aspartate receptors by haloperidol | journal = Molecular Pharmacology | volume = 50 | issue = 6 | pages = 1541–1550 | date = December 1996 | pmid = 8967976 | url = http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8967976 }}</ref>

|}

== Pharmacokinetics ==

=== By mouth ===

The [[bioavailability]] of oral haloperidol ranges from 60 to 70%. However, there is a wide variance in reported mean [[Cmax (pharmacology)|T_max]] and [[Biological half-life|T_1/2]] in different studies, ranging from 1.7 to 6.1 hours and 14.5 to 36.7 hours respectively.<ref name=PK1999 >{{cite journal | vauthors = Kudo S, Ishizaki T | title = Pharmacokinetics of haloperidol: an update | journal = Clinical Pharmacokinetics | volume = 37 | issue = 6 | pages = 435–456 | date = December 1999 | pmid = 10628896 | doi = 10.2165/00003088-199937060-00001 | s2cid = 71360020 }}</ref>

=== Intramuscular injections ===

[[File:Haldol Decanoate.jpg|thumb|right|Haldol Decanoate for injection into muscle<ref name=EMC>{{cite web |title=Haldol Decanoate - Summary of Product Characteristics (SmPC) - (emc) |url=https://www.medicines.org.uk/emc/product/968/smpc |website=www.medicines.org.uk |access-date=26 December 2021}}</ref>]]

The drug is well and rapidly absorbed with a high bioavailability when injected intramuscularly. The T_max is 20 minutes in healthy individuals and 33.8 minutes in patients with schizophrenia. The mean T_1/2 is 20.7 hours.<ref name=PK1999 /> The [[decanoate]] injectable formulation is for intramuscular administration only and is not intended to be used intravenously. The plasma concentrations of haloperidol decanoate reach a peak at about six days after the injection, falling thereafter, with an approximate half-life of three weeks.<ref>{{cite web |url = https://www.drugs.com/pro/haldol-decanoate.html |title = drugs.com |url-status = live |archive-url = https://web.archive.org/web/20110810064415/http://www.drugs.com/pro/haldol-decanoate.html |archive-date = 2011-08-10 }}</ref>

=== Intravenous injections ===

The bioavailability is 100% in intravenous (IV) injection, and the very rapid onset of action is seen within seconds. The T_1/2 is 14.1 to 26.2 hours. The apparent volume of distribution is between 9.5 and 21.7 L/kg.<ref name=PK1999 /> The duration of action is four to six hours.

=== Therapeutic concentrations ===

Plasma levels of five to 15 micrograms per liter are typically seen for therapeutic response (Ulrich S, et al. Clin Pharmacokinet. 1998). The determination of plasma levels is rarely used to calculate dose adjustments but can be useful to check compliance.

The concentration of haloperidol in brain tissue is about 20-fold higher compared to blood levels. It is slowly eliminated from brain tissue,<ref name="Kornhuber1999">{{cite journal | vauthors = Kornhuber J, Schultz A, Wiltfang J, Meineke I, Gleiter CH, Zöchling R, Boissl KW, Leblhuber F, Riederer P | display-authors = 6 | title = Persistence of haloperidol in human brain tissue | journal = The American Journal of Psychiatry | volume = 156 | issue = 6 | pages = 885–890 | date = June 1999 | pmid = 10360127 | doi = 10.1176/ajp.156.6.885 }}</ref> which may explain the slow disappearance of side effects when the medication is stopped.<ref name="Kornhuber1999" /><ref>{{cite journal | vauthors = Kornhuber J, Wiltfang J, Riederer P, Bleich S | title = Neuroleptic drugs in the human brain: clinical impact of persistence and region-specific distribution | journal = European Archives of Psychiatry and Clinical Neuroscience | volume = 256 | issue = 5 | pages = 274–280 | date = August 2006 | pmid = 16788768 | doi = 10.1007/s00406-006-0661-7 | s2cid = 9565741 }}</ref>

=== Distribution and metabolism ===

Haloperidol is heavily protein bound in human plasma, with a free fraction of only 7.5 to 11.6%. It is also extensively metabolized in the liver with only about 1% of the administered dose excreted unchanged in the urine. The greatest proportion of the hepatic clearance is by [[glucuronidation]], followed by reduction and CYP-mediated oxidation, primarily by [[CYP3A4]].<ref name=PK1999 />

== History ==

Haloperidol was discovered by [[Paul Janssen]].<ref>{{cite book | vauthors = Healy D |author-link = David Healy (psychiatrist) |title = The psychopharmacologists |volume = 1 |year = 1996 |publisher = Chapman and Hall |location = London |isbn = 978-1-86036-008-4 }}{{page needed|date=September 2012}}</ref> It was developed in 1958 at the Belgian company [[Janssen Pharmaceutica]] and submitted to the first of clinical trials in [[Belgium]] later that year.<ref name=":0">{{cite journal | vauthors = Granger B, Albu S | title = The haloperidol story | journal = Annals of Clinical Psychiatry | volume = 17 | issue = 3 | pages = 137–140 | year = 2005 | pmid = 16433054 | doi = 10.1080/10401230591002048 }}</ref><ref name=JanssenHist>{{cite journal | vauthors = López-Muñoz F, Alamo C | title = The consolidation of neuroleptic therapy: Janssen, the discovery of haloperidol and its introduction into clinical practice | journal = Brain Research Bulletin | volume = 79 | issue = 2 | pages = 130–141 | date = April 2009 | pmid = 19186209 | doi = 10.1016/j.brainresbull.2009.01.005 | s2cid = 7720401 }}</ref>

Haloperidol was approved by the [[U.S. Food and Drug Administration]] (FDA) on 12 April 1967; it was later marketed in the U.S. and other countries under the brand name Haldol by [[McNeil Laboratories]].<ref name=":0" />

==Society and culture==

===Cost===

Haloperidol is relatively inexpensive, being up to 100 fold less expensive than newer antipsychotics.<ref name=Es2013>{{cite book | vauthors = Escobar JI, Marin H |title=Clinical Psychopharmacology: A Practical Approach |date=2013 |publisher=World Scientific |isbn=978-981-4578-37-0 |page=69 |url=https://books.google.com/books?id=XPy2CgAAQBAJ&pg=PA69 |language=en}}</ref><ref name=EM2012>{{cite book | vauthors = Adams JG |title=Emergency Medicine E-Book: Clinical Essentials (Expert Consult -- Online) |date=2012 |publisher=Elsevier Health Sciences |isbn=978-1-4557-3394-1 |page=1635 |url=https://books.google.com/books?id=rpoH-KYE93IC&pg=PA1635 |language=en}}</ref>

=== Brand names ===

Haloperidol is the [[International Nonproprietary Name|INN]], [[British Approved Name|BAN]], [[United States Adopted Name|USAN]], [[Australian Approved Name|AAN]] approved name.

It is sold under the tradenames Aloperidin, Bioperidolo, Brotopon, Dozic, Duraperidol (Germany), Einalon S, Eukystol, Haldol (common tradename in the US and UK), Halol, Halosten, Keselan, Linton, Peluces, Serenace Norodol (Turkey) and Sigaperidol.{{Citation needed|date=April 2013}}

== Veterinary use ==

Haloperidol is also used on many different kinds of animals for nonselective tranquilization and diminishing behavioral arousal, in veterinary and other settings including captivity management.<ref>{{cite journal | vauthors = Hofmeyr JM | title = The use of haloperidol as a long-acting neuroleptic in game capture operations | journal = Journal of the South African Veterinary Association | volume = 52 | issue = 4 | pages = 273–282 | date = December 1981 | pmid = 6122740 }}</ref>

== References ==

{{Reflist}}

== External links ==

* {{cite web| url = https://druginfo.nlm.nih.gov/drugportal/name/haloperidol | publisher = U.S. National Library of Medicine| work = Drug Information Portal| title = Haloperidol }}

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