Haloperidol Totally Explained

Everything about Haloperidol totally explained

Haloperidol (sold under the tradenames Aloperidin, Bioperidolo, Brotopon, Dozic, Duraperidol (Germany), Einalon S, Eukystol, Haldol, Halosten, Keselan, Linton, Peluces, Serenace, Serenase, Sigaperidol) is a conventional, or typical, butyrophenone antipsychotic drug with pharmacological effects similar to the phenothiazines.
Haloperidol is used in the treatment of schizophrenia and, more acutely, in the treatment of acute psychotic states and delirium. A long-acting decanoate ester is used as a long acting injection given every 4 weeks to people with schizophrenia or related illnesses who have a poor compliance with medication and suffer frequent relapses of illness. In some countries this can be involuntary under Community Treatment Orders.
It was developed in 1957 by the Belgian company Janssen Pharmaceutica and submitted to first clinical trials in Belgium in the same year. After being rejected by U.S. company Searle due to side effects, it was later marketed in the U.S. by McNeil Laboratories. It was approved by the FDA in 1988.

Chemical structure

Haloperidol is an odorless white to yellow crystalline powder. It contains two chemical benzene rings with a piperidine molecule bonded in between. One benzene ring is bonded with the element chlorine and the other benzene ring is bonded with the element fluorine.

Pharmacology

Haloperidol is a neuroleptic and a butyrophenone. Due to its strong central antidopaminergic action, it's classified as a highly potent neuroleptic. It is approximately 50 times more potent than chlorpromazine on a weight basis (50mg chlorpromazine are equivalent to 1mg haloperidol). Haloperidol possesses a strong activity against delusions and hallucinations, most likely due to an effective dopaminergic receptor blockage in the mesocortex and the limbic system of the brain. It blocks the dopaminergic action in the nigrostriatal pathways, which is the probable reason for the high frequency of extrapyramidal-motoric side-effects (dystonias, akathisia, pseudoparkinsonism). It has minor antihistaminic and anticholinergic properties, therefore cardiovascular and anticholinergic side-effects such as hypotension, dry mouth, constipation, etc., are seen quite infrequently, compared with less potent neuroleptics such as chlorpromazine. Haloperidol also has sedative properties and displays a strong action against psychomotor agitation but due to a specific action in the limbic system. It therefore is an effective treatment for mania and states of agitation. Additionally, it can be given as an adjuvant in the therapy of severe chronic pain.
The peripheral antidopaminergic effects of haloperidol account for its strong antiemetic activity. There, it acts at the chemoreceptor trigger zone (CTZ). Haloperidol is useful to treat severe forms of nausea/emesis such as those resulting from chemotherapy. The peripheral effects lead also to a relaxation of the gastric sphincter muscle and an increased release of the hormone prolactin, with the possible emergence of breast enlargement and secretion of milk (lactation) in both sexes.

Pharmacokinetics

Intramuscular injections

The drug is well and rapidly absorbed and has a high bioavailability. Plasma-levels reach their maximum within 20 minutes after injection. The decanoate injectable formulation is for intramuscular administration only and should never be used intravenously.

Intravenous injections

The bioavailability is 100% and the very rapid onset of action is seen within about ten minutes. The duration of action is 3 to 6 hours. If haloperidol is given as slow IV infusion, the onset of action is retarded, but the duration prolonged compared to IM injection.

Therapeutic concentrations

Plasma levels of 4 micrograms per liter to 20 (up to 25) micrograms per liter are required for therapeutic action. The determination of plasma levels can be used to calculate dose adjustments and to check compliance, particularly in long-term patients. Plasma levels in excess of the therapeutic range may lead to a higher incidence of side-effects or even pose the risk of haloperidol intoxication.

Uses

A comprehensive review of haloperidol has found it to be an effective agent in treatment of symptoms associated with schizophrenia. Haloperidol is also used in the control of the symptoms of:

Acute psychosis, such as drug psychosis (LSD, psilocybin, amphetamines), psychosis associated with high fever or metabolic disease
Acute manic phases until the concomitantly given first-line drugs such as lithium or valproate are effective
Hyperactivity, aggression.
Acute delirium
Otherwise uncontrollable severe behavioral disorders in children and adolescents
Agitation and confusion associated with cerebral sclerosis
Adjunctive treatment of alcohol and opioid withdrawal
Treatment of neurological disorders such as tic disorders, Tourette syndrome, and chorea
Treatment of severe nausea/emesis (postoperative, side-effects of radiation and cancer chemotherapy)
Adjunctive treatment of severe chronic pain, always together with analgesics
Therapeutic trial in personality disorders such as borderline personality disorders
Also used in the treatment of Intractable hiccups

Some weeks or even months of treatment may be needed before a remission of schizophrenia is evident.
In some clinics the use of atypical neuroleptics (for example clozapine, risperidone, olanzapine, ziprasidone) is generally preferred over haloperidol, because these drugs have an appreciably lower incidence of extrapyramidal side-effects. Each of these drugs, however, has its own spectrum of potentially serious side-effects (for example agranulocytosis with clozapine, weight gain with increased risk of diabetes and of stroke). Atypical neuroleptics are also much more expensive and have recently been the subject of increasing controversy regarding their efficacy in comparison to older products and side effects.
Haloperidol was considered indispensable for treating psychiatric emergency situations, although the newer atypical drugs have gained greater role in a number of situations as outlined in a series of consensus reviews published between 2001 and 2005. The study concluded that
The television show Twin Peaks includes an instance in which Haloperidol is used during an interrogation as a truth serum. There is no recorded history of Haloperidol actually being used for this purpose, and many of the effects on the show seem to be the opposite of the drugs actual effects (including the induction of a psychotic state).

Contraindications

Absolute

Preexisting 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 caution needed

Preexisting Parkinson's disease

Patients at special risk for the development of QT prolongation (hypokalemia, concomitant use of other drugs causing QT prolongation)

Compromised liver-function (as haloperidol is metabolized and eliminated mainly by the liver, dose reductions and/or spaced intervals may be needed)

Haloperidol may decrease the seizure-threshold. Treat patients with epilepsy and those with risk factors for the development of seizures (alcohol withdrawal, encephalopathy) with caution. Maintain existing anticonvulsive therapy.

Patients with hyperthyreosis; the action of haloperidol is intensified and side-effects are more likely. Initiate an effective therapy of hyperthyreosis.

IV injections: inject slowly to avoid hypotension or orthostatic collapse. Avoid IV injections in cardiovascular unstable patients (preexisting hypotension, shock, concomitant antihypertensive therapy, heart insufficiency). Prefer in these cases moderate oral or IM doses.

Adverse effects

The drug is noted for its strong early and late extrapyramidal side-effects. These results need confirmation by larger studies. If true, carcinogenity is most probably related to the strong increase in plasma-levels of prolactin under long-term treatment with haloperidol. This news is another good reason to avoid any unnecessary use of haloperidol.

Interactions

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%.

Methyldopa: increased risk of extrapyramidal side-effects and other unwanted central effects

Levodopa: decreased action of levodopa

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

Quinidine, buspirone, and fluoxetine: increased plasma-levels of haloperidol, decrease haloperidol dose, if necessary

Carbamazepine, phenobarbital, and rifampicin: plasma-levels of haloperidol significantly decreased, increase haloperidol dose, if necessary.

lithium: rare cases of the following symptoms have been noted: encephalopathy, early and late extrapyramidal side-effects, other neurologic symptoms and coma. Check lithium plasma levels regularly and keep the dose of haloperidol as low as possible.

Guanethidine: antihypertensive action antagonized

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

Doses

As directed by the physician, depends on the condition to be treated, age and weight of patient:

Acute problems: single doses of 1 mg to 5 mg (up to 10mg) oral or i.m., usually repeated every 4 to 8 hours. Do not exceed an oral dose of 100 mg daily. Doses used for IV injection are usually 5 to 10 mg as a single dose; not exceeding 50 mg daily.

Chronic conditions: 0.5 to 20 mg daily oral, rarely more. The lowest dose that maintains remission should be employed.

Experimental doses: In resistant cases of psychosis small studies with oral doses of up to 300 mg daily have been conducted (in most cases together with an anticholinergic antiparkinsonian drug (Biperiden, Benzatropine, etc.) to avoid severe early extrapyramidal side-effects. These studies showed no superior results and led to severe side-effects. Also, the frequency of otherwise unusual side-effects (hypotension, QT-time prolongation, and serious cardiac arrhythmias) was dramatically increased. The clinical use of haloperidol in these doses is discouraged now and it's recommended to switch the patient gradually to a different neuroleptic (for example clozapine, olanzapine, aripiprazole). Depot forms are also available; these are injected deeply i.m. at regular intervals. The depot forms are not suitable for initial treatment

Overdose

Experimental evidence from animal studies indicates that doses needed for acute poisoning are quite high in relation to therapeutic doses.
Overdoses with depot injections are uncommon, because almost always experienced personnel administer them to patients.

Symptoms

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

Severe extrapyramidal side-effects with muscle rigidity and tremors, akathisia etc. (inject 5 mg biperiden (Akineton) slowly IV, repeat after some hours if necessary). Sometimes oral or IM treatment with biperiden is needed for several days or even weeks. If the patient is very upset about extrapyramidal side-effects, small doses of lorazepam (0.5 to 1 mg orally, repeated every 4 to 6 hours if necessary) can be given. Lorazepam has an intrinsic action against upset, anxiety, and extrapyramidal side-effects.

Hypotension or hypertension

Sedation

Anticholinergic side-effects (dry mouth, constipation, paralytic ileus, difficulties in urinating, massive sweating). Cautious doses of physostigmine may be given repeatedly. Physostigmine may increase the risk of seizures.

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

Rarely serious ventricular arrhythmia (torsades de pointes) with or without prolonged QT-time

Epileptic seizures, give careful doses of diazepam 5 mg to 10 mg by slow IV injection, repeatedly if needed, until seizures subside. Take care not to worsen central depression or respiratory depression caused by haloperidol. The treatment facility should be able to institute artificial respiration readily. Valproate first given as slow IV infusion and later orally may also be effective.

Treatment

Treatment is merely 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 all be tried. Avoid epinephrine for treatment of hypotension and shock, because its action might be reversed.

Prognosis

Generally, the prognosis of overdose is good and lasting damage isn't known, provided that the patient has survived the initial phase.

Other formulations

The decanoate ester of haloperidol (Haloperidol decanoate, trade names Haldol decanoate, Halomonth, Neoperidole) has a much longer duration of action, and therefore is used in noncompliant people. A dose of 25 to 250 mg is given by intramuscular injection once every two to four weeks.
The IUPAC name of haloperidol decanoate is 4-(4-chlorophenyl)-1-1[4-(4-fluorophenyl)-4-oxobutyl]-4 piperidinyl decanoate.

Veterinary use

Haloperidol is also used on many different kinds of animals. It appears to be particularly successful when given to birds; for example a parrot that won't otherwise stop plucking its feathers out.

Dose forms

Liquid: 2 mg/mL, also 10 mg/mL

Tablets: 0.5 mg, 1 mg, 2 mg, 5 mg, 10 mg, 20 mg

Injection: 5 mg (1 mL)

Depot injection forms

The original drug Haldol and many generics are availableFurther Information

Get more info on 'Haloperidol'.

External Link Exchanges

Do you know how hard it is to get a link from a large encyclopaedia? Well we're different and will prove it. To get a link from us just add the following HTML to your site on a relevant page:

<a href="http://haloperidol.totallyexplained.com">Haloperidol Totally Explained</a>

Then simply click through this link from your web page. Our crawlers will verify your link, extract the title of your web page and instantly add a link back to it. If you like you can remove the words Totally Explained and embed the link in article text.
As long as your link remains in place, we'll keep our link to you right here. Please play fair - our crawlers are watching. Your site must be closely related to this one's topic. Any kind of spamming, dubious practises or removing the link will result in your link from us being dropped and, potentially, your whole site being banned.