Editing Haloperidol (section)

== 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 = 29 May 2014 |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><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 = 29 September 2013 |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 = 14 March 2017 }}</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 = 30 September 2016 |url-status = dead |archive-url = https://web.archive.org/web/20170119063641/https://www.fda.gov/ohrms/dockets/ac/00/backgrd/3619b1a.pdf |archive-date = 19 January 2017 }}</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>

Prolonged use of the drug can lead to mental dependence.<ref>{{Cite web|url=https://consensus.app/questions/haloperidol-withdrawal-symptoms/|title=Haloperidol Withdrawal Symptoms: An Overview}}</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 | 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=1 April 2008 | url=http://news.bbc.co.uk/1/hi/health/7319393.stm | access-date=3 August 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 irreversibly blocks the [[sigma receptor|sigma]] [[sigma-1 receptor|σ<sup>1</sup> receptor]].<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 }}</ref>  It 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> Besides the preceding mechanisms, haloperidol metabolizes into [[HPP+|HPP<sup>+</sup>]], a [[monoaminergic neurotoxin]] related to [[MPTP]].<ref name="Kostrzewa2022" /><ref name="Igarashi1998" /><ref name="GórskaMarszałłSloderbach2015" /> This might be involved in the [[extrapyramidal symptoms]] that develop with long-term haloperidol therapy.<ref name="Kostrzewa2022" /><ref name="Igarashi1998" /><ref name="GórskaMarszałłSloderbach2015" />

===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/>