haloperidol haloperidol haloperidol, sold under the brand name haldol among others, is a typical antipsychotic medication. 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. it may be used by mouth or injection into a muscle or a vein. haloperidol typically works within 30 to 60 minutes. 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. haloperidolclinical datapronunciation/ˌhæloʊˈpɛrɪdɒl/ trade nameshaldol, serenace, othersahfs/drugs.commonographmedlineplusa682180license data us dailymed: haloperidol pregnancycategory au: c routes ofadministrationby mouth, intramuscular, intravenous, depot (as decanoate ester)drug classtypical antipsychoticatc coden05ad01 (who) legal statuslegal status au: s4 (prescription only) ca: ℞-only uk: pom (prescription only) us: ℞-only pharmacokinetic databioavailability60–70% (by mouth)protein binding~90%metabolismliver-mediatedelimination half-life14–26 hours (iv), 20.7 hours (im), 14–37 hours (oral)excretionbiliary (hence in feces) and in urineidentifiers iupac name 4--1-(4-fluorophenyl)butan-1-one cas number52-86-8 ypubchem cid3559iuphar/bps86drugbankdb00502 ychemspider3438 yuniij6292f8l3dkeggd00136 ychebichebi:5613 ychemblchembl54 ycomptox dashboard (epa)dtxsid4034150 echa infocard100.000.142 chemical and physical dataformulac21h23clfno2molar mass375.87 g·mol−13d model (jsmol)interactive image smiles c1cc(ccc1c(=o)cccn2ccc(cc2)(c3ccc(cc3)cl)o)f inchi inchi=1s/c21h23clfno2/c22-18-7-5-17(6-8-18)21(26)11-14-24(15-12-21)13-1-2-20(25)16-3-9-19(23)10-4-16/h3-10,26h,1-2,11-15h2 ykey:lnepoxffqsencj-uhfffaoysa-n y (verify) several lines of significant scientific evidence demonstrate that haloperidol exhibits potent neurotoxicity at all doses via many molecular mechanisms that lead to neuronal death. several published studies have reported an association between antipsychotic medications, especially first-generation agents, and a decline in gray matter volume. haloperidol may exert deleterious effects on the dorsolateral prefrontal cortex (dlpfc) by attenuating bdnf transcript and bdnf protein expression with a concomitant increase in the long non-coding rna bdnf-as in the dlpfc, suggesting a potential role for haloperidol-induced decreases in bdnf expression in this region. haloperidol may result in a movement disorder known as tardive dyskinesia which may be permanent. neuroleptic malignant syndrome and qt interval prolongation may occur. in older people with psychosis due to dementia it results in an increased risk of death. when taken during pregnancy it may result in problems in the infant. it should not be used by people with parkinson's disease. haloperidol was discovered in 1958 by paul janssen, prepared as part of a structure-activity relationship investigation into analogs of pethidine (meperidine). it is on the world health organization's list of essential medicines. it is the most commonly used typical antipsychotic. in 2020, it was the 303rd most commonly prescribed medication in the united states, with more than 1 million prescriptions. physicochemical properties haloperidol is a crystalline material with a melting temperature of 150 °c. this drug has very very low solubility in water (1.4 mg/100 ml), but it is soluble in chloroform, benzene, methanol, and acetone. it is also soluble in 0.1 m hydrochloric acid (3 mg/ml) with heating. medical uses haloperidol is used in the control of the symptoms of: acute psychosis, such as drug-induced psychosis caused by, amphetamines, ketamine, and phencyclidine, and psychosis associated with high fever or metabolic disease. some evidence, however, has found haloperidol to worsen psychosis due to psilocybin. adjunctive treatment of alcohol and opioid withdrawal agitation and confusion associated with cerebral sclerosis alcohol-induced psychosis hallucinations in alcohol withdrawal hyperactive delirium (to control the agitation component of delirium) hyperactivity, aggression otherwise uncontrollable, severe behavioral disorders in children and adolescents schizophrenia therapeutic trial in personality disorders, such as borderline personality disorder treatment of intractable hiccups treatment of neurological disorders, including tic disorders such as tourette syndrome, and 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 cannabis hyperemesis syndrome. haloperidol was considered indispensable for treating psychiatric emergency situations, 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. 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. a 2013 systematic review compared haloperidol to placebo in schizophrenia: 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. outcome findings in words findings in numbers quality of evidence general outcomes no marked global improvementfollow-up: >6–24 weekshaloperidol, when compared with placebo, reduces the chance of experiencing 'no improvement'. data are based on moderate quality evidence. rr 0.67 (0.58 to 0.78)moderate not discharged from hospitalfollow-up: > 6–24 weekshaloperidol 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. rr 0.85 (0.47 to 1.52)very low relapsefollow-up: < 52 weekshaloperidol may reduce the chance of relapse, but, at present there is only very limited data supporting this finding. rr 0.69 (0.55 to 0.86)very low leaving the study early follow-up: > 6–24 weekshaloperidol 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. rr 0.54 (0.29 to 1)moderate adverse effects – movement disorders parkinsonismfollow-up: 3 weeks to 3 monthshaloperidol substantially increases the risk of movement disorders. data are based on moderate quality evidence. rr 5.48 (2.68 to 11.22)moderate missing outcomes severe adverse events, such as death, and outcomes such as satisfaction with treatment were not measured/reported in the included studies. pregnancy and lactation data from 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 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. 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. other considerations skeletal formula of haloperidol decanoate. the decanoate group is highlighted in 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. 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. other forms of therapy (psychotherapy, occupational therapy/ergotherapy, or social rehabilitation) should be instituted properly. 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 mg increased the risk of side effects without improving efficacy. patients responded with doses under even 2 mg in first-episode psychosis. 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. 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. 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. the iupac name of haloperidol decanoate is piperidin-4-yl] decanoate. topical formulations of haloperidol should not be used as treatment for nausea because research does not indicate this therapy is more effective than alternatives. adverse effects sources for the following lists of adverse effects: 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. with more than 6 months of use 14 percent of users gain weight. haloperidol may be neurotoxic. 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.) unknown frequency anemia headache increased respiratory rate orthostatic hypotension prolonged qt interval visual disturbances rare (<1% incidence) acute hepatic failure agitation agranulocytosis anaphylactic reaction anorexia bronchospasm cataracts cholestasis confusional state depression dermatitis exfoliative dyspnea edema extrasystoles 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 psychotic disorder pulmonary embolism rash retinopathy seizure sudden death tardive dyskinesia thrombocytopenia torsades de pointes urinary retention urticaria ventricular fibrillation ventricular tachycardia vomiting 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 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. 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. 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 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. pre-existing parkinson's disease or dementia with lewy bodies interactions amiodarone: q-tc interval prolongation (potentially dangerous change in heart rhythm). amphetamine and methylphenidate: counteracts increased action of norepinephrine and dopamine in patients with narcolepsy or add/adhd epinephrine: action antagonized, paradoxical decrease in blood pressure may result guanethidine: antihypertensive action antagonized levodopa: decreased action of levodopa lithium: rare cases of the following symptoms have been noted: encephalopathy, early and late extrapyramidal side effects, other neurologic symptoms, and coma. 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 tricyclic antidepressants: metabolism and elimination of tricyclics significantly decreased, increased toxicity noted (anticholinergic and cardiovascular side effects, lowering of seizure threshold) discontinuation the british national formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. symptoms of withdrawal commonly include nausea, vomiting, and