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.[4][5] 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 for people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.
Haloperidol may result in movement disorders such as tardive dyskinesia, and akathisia, both of which may be permanent. Neuroleptic malignant syndrome and QT interval prolongation may occur, the latter particularly with IV administration. In older people with psychosis due to dementia it results in an increased risk of death.[6] When taken during pregnancy it may result in problems in the infant.[6][7] It should not be used by people with Parkinson's disease.[6]
Haloperidol was discovered in 1958 by the team of Paul Janssen,[8] prepared as part of a structure-activity relationship investigation into analogs of pethidine (meperidine).[9] It is on the World Health Organization's List of Essential Medicines.[10] It is the most commonly used typical antipsychotic.[11] In 2020, it was the 303rd most commonly prescribed medication in the United States, with more than 1million prescriptions.[12]
Medical uses
Haloperidol is used in the control of the symptoms of:
Haloperidol was considered indispensable for treating psychiatric emergency situations.[18][19] However, 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.[20][21][22]
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.[23]
Adverse effects
Sources for the following lists of adverse effects:[35][36][37][38]
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.[23]
With more than 6 months of use 14 percent of users gain weight.[39] Haloperidol may be neurotoxic.[40]
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 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
Pharmacology
Haloperidol is a typical butyrophenone-type antipsychotic that exhibits high-affinity dopamine D2 receptor antagonism and slow receptor dissociation kinetics.[57] It has effects similar to the phenothiazines.[58] The drug binds preferentially to D2 and α1 receptors at low dose (ED50 = 0.13 and 0.42 mg/kg, respectively), and 5-HT2 receptors at a higher dose (ED50 = 2.6 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.[59] 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 symptoms.
Pharmacokinetics
By mouth
Chemistry
Haloperidol is a crystalline material with a melting temperature of 150 °C.[76] This drug has 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.[77]
History
Haloperidol was discovered by Paul Janssen.[78] It was developed in 1958 at the Belgian company Janssen Pharmaceutica and submitted to the first of clinical trials in Belgium later that year.[79][80]
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.[79]
Society and culture
Cost
Haloperidol is relatively inexpensive, being up to 100 fold less expensive than newer antipsychotics.[81][82]
Names
Haloperidol is the INN, BAN, USAN, 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.
Research
Haloperidol was under investigation for the treatment of depression.[83][84] It was employed as a short-term low-dose dopamine receptor antagonist to upregulate dopamine receptors and produce receptor supersensitivity followed by drug withdrawal as a means of treating depression.[83][85][84]
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.[86]
References
- Haloperidol Use During Pregnancy Drugs.com, 10 February 2020, retrieved 13 September 2020^
- Anvisa. RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial Diário Oficial da União, 31 March 2023, retrieved 16 August 2023^
- Product Information Serenace