Haloperidol is a
typical antipsychoticTypical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis...
. It is in the
butyrophenoneButyrophenone is a chemical compound ; some of its derivatives are used to treat various psychiatric disorders such as schizophrenia, as well as acting as antiemetics....
class of
antipsychoticAn antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
medications and has
pharmacological effectsPharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
similar to the
phenothiazinePhenothiazine is an organic compound that occurs in various antipsychotic and antihistaminic drugs. It has the formula S2NH. This yellow tricyclic compound is soluble in acetic acid, benzene, and ether. The compound is related to the thiazine-class of heterocyclic compounds...
s.
Haloperidol is an older antipsychotic used in the treatment of
schizophreniaSchizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
and, more acutely, in the treatment of acute
psychoticPsychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
states and
deliriumDelirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
. A long-acting decanoate
esterEsters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
is used as an injection given every 4 weeks to people with
schizophreniaSchizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
or related illnesses who have a poor compliance with medication and suffer frequent relapses of illness, or to overcome the drawbacks inherent to its orally administered counterpart that burst dosage increases risk or intensity of side effects. In some countries, injections of antipsychotics such as haloperidol can be ordered by a court at the request of a psychiatrist.
Haloperidol is sold under the tradenames
Aloperidin,
Bioperidolo,
Brotopon,
Dozic,
Duraperidol (Germany),
Einalon S,
Eukystol,
Haldol,
Halosten,
Keselan,
Linton,
Peluces,
Serenace,
Serenase, and
Sigaperidol.
History
Haloperidol was discovered by
Paul JanssenPaul Adriaan Jan, Baron Janssen was the founder of Janssen Pharmaceutica, a pharmaceutical company with over 20,000 employees. In 2005 he finished as runner up, after Father Damien, in the poll for The Greatest Belgian organized by the regional Flemish television...
. It was developed in 1958 by the Belgian company
Janssen PharmaceuticaJanssen Pharmaceutica is pharmaceutical company, established in Belgium in 1953 by Paul Janssen. Its headquarters are located in Beerse, in the Campine region of the province of Antwerp, Belgium. It was created not as a subsidiary of a chemical factory but solely with the aim of conducting...
and submitted to the first of clinical trials in
BelgiumBelgium , officially the Kingdom of Belgium, is a federal state in Western Europe. It is a founding member of the European Union and hosts the EU's headquarters, and those of several other major international organisations such as NATO.Belgium is also a member of, or affiliated to, many...
later that year.
Haloperidol was approved by the U.S. Food and Drug Administration (FDA) on April 12, 1967, later marketed in the U.S. and other countries under the brand name
Haldol by
McNeil LaboratoriesMcNeil Consumer Healthcare is a medicals products company belonging to the Johnson & Johnson healthcare products group.-History:The company was founded on March 16, 1879 by 23-year-old Robert McNeil, who paid $167 for a drugstore complete with fixtures, inventory and soda fountain, as a retail...
.
Pharmacology
Haloperidol is an
antipsychoticAn antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
butyrophenoneButyrophenone is a chemical compound ; some of its derivatives are used to treat various psychiatric disorders such as schizophrenia, as well as acting as antiemetics....
. Due to its strong central anti
dopaminergicDopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
action, it is classified as a highly potent neuroleptic. It is approximately 50 times more potent than
chlorpromazineChlorpromazine is a typical antipsychotic...
(sold under the brand name Thorazine, among others) on a weight basis (50 mg chlorpromazine is equivalent to 1 mg haloperidol). Haloperidol possesses a strong activity against delusions and hallucinations, most likely due to an effective
dopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
rgic receptor blockage in the mesocortex and the
limbic systemThe limbic system is a set of brain structures including the hippocampus, amygdala, anterior thalamic nuclei, septum, limbic cortex and fornix, which seemingly support a variety of functions including emotion, behavior, long term memory, and olfaction. The term "limbic" comes from the Latin...
of the brain. It blocks the
dopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
rgic action in the
nigrostriatal pathwayThe nigrostriatal pathway is a neural pathway that connects the substantia nigra with the striatum. It is one of the four major dopamine pathways in the brain, and is particularly involved in the production of movement, as part of a system called the basal ganglia motor loop.Loss of dopamine...
s, which is the probable reason for the high frequency of
extrapyramidalIn human anatomy, the extrapyramidal system is a neural network located in the brain that is part of the motor system involved in the coordination of movement. The system is called "extrapyramidal" to distinguish it from the tracts of the motor cortex that reach their targets by traveling through...
-motoric side effects (
dystoniaDystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...
s,
akathisiaAkathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
,
pseudoparkinsonismParkinson's disease is a degenerative disorder of the central nervous system...
).
Haloperidol has minor
antihistaminicHistamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
and
anticholinergicAn anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
properties, therefore cardiovascular and anticholinergic side effects such as
hypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, dry mouth,
constipationConstipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
, etc. are seen quite infrequently, compared with less-potent neuroleptics such as chlorpromazine. Haloperidol also has
sedativeA sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
properties and displays a strong action against
psychomotorPsychomotor can refer to:* Psychomotor learning* Psychomotor retardation* Psychomotor agitation...
agitation due to a specific action in the
limbic systemThe limbic system is a set of brain structures including the hippocampus, amygdala, anterior thalamic nuclei, septum, limbic cortex and fornix, which seemingly support a variety of functions including emotion, behavior, long term memory, and olfaction. The term "limbic" comes from the Latin...
. However, in some cases, haloperidol may worsen psychomotor agitation via its potent
dopamine receptorDopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....
antagonism. Dopamine receptor antagonism, mainly of the D2 receptor subtype, can cause
akathisiaAkathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
, psychomotor agitation, anxiety, and restlessness, which may worsen the condition of some patients.
The peripheral antidopaminergic effects of haloperidol account for its strong
antiemeticAn antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer....
activity. There, it acts at the
chemoreceptor trigger zoneThe chemoreceptor trigger zone , is an area of the medulla that receives inputs from blood-borne drugs or hormones, and communicates with the vomiting center, to initiate vomiting. The CTZ is close to the area postrema on the floor of the fourth ventricle and is outside of the blood-brain barrier...
(CTZ). Haloperidol is useful to treat severe forms of nausea/emesis such as those resulting from
chemotherapyChemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
. The peripheral effects lead also to a relaxation of the gastric
sphincterA sphincter is an anatomical structure, or a circular muscle, that normally maintains constriction of a natural body passage or orifice and which relaxes as required by normal physiological functioning...
muscle and an increased release of the hormone
prolactinProlactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
, with the possible emergence of
breastThe breast is the upper ventral region of the torso of a primate, in left and right sides, which in a female contains the mammary gland that secretes milk used to feed infants.Both men and women develop breasts from the same embryological tissues...
enlargement and secretion of milk (
galactorrheaGalactorrhea or galactorrhoea is the spontaneous flow of milk from the breast, unassociated with childbirth or nursing.Contemporary Maternal-Newborn Nursing Care defines galactorrhea as "nipple discharge." -Causes:...
) in both sexes.
Intramuscular injections
The drug is well and rapidly absorbed with a high bioavailability.
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 6 days after the injection, falling thereafter, with an approx. half-life of 3 weeks.
Intravenous injections
The bioavailability is 100% and the very rapid onset of action is seen within seconds.
The duration of action is 4–6 hours. If haloperidol is given as a slow IV infusion, the onset of action is slowed, and the duration of action is prolonged.
Therapeutic concentrations
Plasma levels of 4 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.
The concentration of haloperidol in brain tissue is about 20fold higher compared to blood levels. Haloperidol is slowly eliminated from brain tissue, which may explain the slow disappearence of side-effects when haloperdol medication is stopped.
Uses
A comprehensive review of haloperidol has found it to be an effective agent in treatment of symptoms associated with
schizophreniaSchizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
.
Haloperidol is also used in the control of the symptoms of:
- Acute psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
, such as drug psychosis (LSD, psilocybin, amphetamines, ketamine, and phencyclidine), psychosis associated with high fever or metabolic disease
- Acute manic phases
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...
until the concomitantly given first-line drugs such as lithiumLithium pharmacology refers to use of the lithium ion, Li+, as a drug. A number of chemical salts of lithium are used medically as a mood stabilizing drug, primarily in the treatment of bipolar disorder, where they have a role in the treatment of depression and particularly of mania, both acutely...
or valproate are effective
- Hyperactivity, aggression
In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause humiliation, pain, or harm. Ferguson and Beaver defined aggressive behavior as "Behavior which is intended to increase the social dominance of...
.
- Acute delirium
Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
- Otherwise uncontrollable severe behavioral disorders in children and adolescents
- Agitation and confusion associated with cerebral sclerosis
In medicine, sclerosis refers to the stiffening of a structure, usually caused by a replacement of the normal organ-specific tissue with connective tissue.Types include:...
- Adjunctive treatment of alcohol and opioid withdrawal
- Treatment of severe nausea and emesis in postoperative and palliative care
Palliative care is a specialized area of healthcare that focuses on relieving and preventing the suffering of patients...
, especially with regards to palliating adverse effects of radiation therapyRadiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
and chemotherapyChemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
in oncologyOncology is a branch of medicine that deals with cancer...
- Treatment of neurological disorders such as tic disorder
Tic disorders are defined in the Diagnostic and Statistical Manual of Mental Disorders based on type and duration of tics...
s, Tourette syndromeTourette syndrome is an inherited neuropsychiatric disorder with onset in childhood, characterized by multiple physical tics and at least one vocal tic; these tics characteristically wax and wane...
, and choreaChoreia is an abnormal involuntary movement disorder, one of a group of neurological disorders called dyskinesias. The term choreia is derived from the Greek word χορεία , see choreia , as the quick movements of the feet or hands are vaguely comparable to dancing or piano playing.The term...
- Adjunctive treatment of severe chronic pain, always together with analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
s
- Therapeutic trial in personality disorders such as borderline personality disorder
Borderline personality disorder is a personality disorder described as a prolonged disturbance of personality function in a person , characterized by depth and variability of moods.The disorder typically involves unusual levels of instability in mood; black and white thinking, or splitting; the...
- Also used in the treatment of intractable hiccups
In Aquaculture
- Also used to block dopamine receptor to enable GnrHA function for ovulation use in spawning fish.
Some weeks or even months of treatment may be needed before a remission of schizophrenia is evident.
In some clinics, the use of
atypical neurolepticsThe atypical antipsychotics are a group of antipsychotic tranquilizing drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA approved for use in the treatment of schizophrenia...
(e.g.,
clozapineClozapine is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder. Wyatt. R and Chew...
,
risperidoneRisperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism...
,
olanzapineOlanzapine is an atypical antipsychotic, approved by the FDA for the treatment of schizophrenia and bipolar disorder...
,
ziprasidoneZiprasidone was the fifth atypical antipsychotic to gain FDA approval . In the United States, Ziprasidone is Food and Drug Administration approved for the treatment of schizophrenia, and the intramuscular injection form of ziprasidone is approved for acute agitation in schizophrenic patients...
) is, in general, 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 (e.g., 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 their 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. It is enrolled in the
World Health OrganizationThe World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
List of Essential Medicines.
As is common with typical neuroleptics, haloperidol is by far more active against "positive" psychotic symptoms (delusions, hallucinations, etc.) than against "negative" symptoms (social withdrawal, etc.).
A multi-year UK study by the Alzheimer's Research Trust suggested that this drug and other neuroleptic anti-psychotic drugs commonly given to Alzheimer's patients with mild behavioural problems often make their condition worse. The study concluded that
Controversial non-medical uses
There are multiple reports from Soviet dissidents, including medical staff, on the use of haloperidol in the Soviet Union for punitive purposes or simply to break the prisoners' will. Notable dissidents that were administered haloperidol as part of their court ordered treatment were
Sergei KovalevSergei Kovalev is a Russian human rights activist and politician and a former Soviet dissident and political prisoner.- Early career and arrest :...
and
Leonid PlyushchLeonid Plyushch is a mathematician and Soviet dissident.- Early life and career :Leonid Plyushch was born into a Ukrainian working-class family in 1939 in Naryn, Kirghizia. His father worked as railway foreman, and was killed at the front 1941...
. The accounts of Plyushch in the West, after he was allowed to leave the Soviet Union in 1976, were instrumental in the triggering Western condemnation of Soviet practices at the
World Psychiatric AssociationThe World Psychiatric Association is an international umbrella organisation of psychiatric societies.-Objectives and goals:Originally created to produce world psychiatric congresses, it has evolved to hold regional meetings, to promote professional education and to set ethical, scientific and...
's 1977 meeting. The use of haloperidol in the Soviet Union's psychiatric system was prevalent because it was one of the few psychotropic drugs produced in quantity in the USSR.
Haloperidol has been used for its sedating effects during the deportations of immigrants by the United States Immigration and Customs Enforcement (ICE). During 2002-2008, federal immigration personnel used haloperidol to sedate 356 deportees. By 2008, following court challenges over the practice, haloperidol was given to only 3 detainees. Following lawsuits, U.S. officials changed the procedure so that the drug is administered only by the recommendation of medical personnel and under court order.
Absolute
- Preexisting coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
, 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
Parkinson's disease is a degenerative disorder of the central nervous system...
or dementia with Lewy bodiesDementia with Lewy bodies , also known under a variety of other names including Lewy body dementia, diffuse Lewy body disease, cortical Lewy body disease, and senile dementia of Lewy type, is a type of dementia closely allied to both Alzheimers and Parkinson's Diseases...
- Patients at special risk for the development of QT prolongation
The long QT syndrome is a rare inborn heart condition in which delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsade de pointes . These episodes may lead to palpitations, fainting and sudden death due to ventricular fibrillation...
(hypokalemiaHypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
, concomitant use of other drugs causing QT prolongation)
- Compromised liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
-function (as haloperidol is metabolized and eliminated mainly by the liver)
- Patients with hyperthyreosis; the action of haloperidol is intensified and side-effects are more likely.
- IV injections: risk of hypotension or orthostatic collapse.
Adverse effects
Haloperidol is noted for its strong early and late
extrapyramidal side effectThe extrapyramidal system can be affected in a number of ways, which are revealed in a range of extrapyramidal symptoms , also known as extrapyramidal side-effects , such as akinesia and akathisia .Extrapyramidal symptoms are various movement disorders such as acute dystonic reactions,...
s.
The risk of the facial disfiguring
tardive dyskinesiaTardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
is around 4% per year in younger patients. Other predispositive factors may be female gender, preexisting affective disorder, and cerebral dysfunction.
AkathisiaAkathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
often manifests itself with anxiety, dysphoria, and an inability to remain motionless.
Other side effects include dry mouth, lethargy, restlessness of
akathisiaAkathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
,
muscleMuscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
-stiffness, muscle-cramping, restlessness,
tremorA tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...
s,
Rabbit syndromeRabbit syndrome is a rare form of extrapyramidal side effect of antipsychotic drugs in which perioral tremors occur at a rate of 5 Hz. Rabbit syndrome is characterized by involuntary, fine, rhythmic motions of the mouth along a vertical plane, without involvement of the tongue...
, and
weightIn science and engineering, the weight of an object is the force on the object due to gravity. Its magnitude , often denoted by an italic letter W, is the product of the mass m of the object and the magnitude of the local gravitational acceleration g; thus:...
-gain; side effects like these are more likely to occur when the drug is given in high doses and/or during long-term treatment.
DepressionMajor depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, severe enough to result in
suicideSuicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...
, is quite often seen during long-term treatment. Care should be taken to detect and treat depression early in course. Sometimes the change from haloperidol to a mildly potent neuroleptic (e.g.,
chlorprothixeneChlorprothixene is a typical antipsychotic drug of the thioxanthene class and was the first of the series to be synthesized...
or
chlorpromazineChlorpromazine is a typical antipsychotic...
), together with appropriate antidepressant therapy, does help. Sedative and anticholinergic side effects occur more frequently in the elderly. The likelihood of one's experiencing one or more of these side-effects is quite high regardless of age and gender, especially with prolonged use.
Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first-generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.
The potentially fatal
neuroleptic malignant syndromeNeuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...
(NMS) is a significant possible side effect. Haloperidol and
fluphenazineFluphenazine is a typical antipsychotic drug used for the treatment of psychoses such as schizophrenia and acute manic phases of bipolar disorder. It belongs to the piperazine class of phenothiazines....
are the two drugs that cause NMS most often. NMS involves fever and other symptoms. Allergic and toxic side effects occur. Skin rash and photosensitivity both occur in fewer than 1% of patients. Children and adolescents are particularly sensitive to the early and late extrapyramidal side effects of haloperidol. It is not recommended to treat pediatric patients.
QT prolongationThe long QT syndrome is a rare inborn heart condition in which delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsade de pointes . These episodes may lead to palpitations, fainting and sudden death due to ventricular fibrillation...
with sudden death is a rarely seen but clinically significant side-effect. Likewise, the development of
thromboembolicThrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
complications are also seen.
Haloperidol may have a negative impact on vigilance or decrease the ability of the patient to drive or operate a machine, particularly initially.
Haloperidol is not devoid of potential psychological dependence. However, due to the debilitating side effects, patients prescribed this drug have a high rate of non-compliance. The current recommendation is to pay close attention to the patient's experience, and taper or discontinue use if the patient has a high rate of dissatisfaction with treatment, as it may lead to dangerously rapid discontinuation.
Haloperidol has been shown to dramatically increase dopamine activity, up to 98%, in test subjects after two weeks on a "moderate to high" dose compared to chronic schizophrenics. In another study, a live survey of a patient showed that the person has 90% more dopamine receptors, of the D2 subtype, than before treatment with haloperidol. The long term effect of this is unknown, but the first study concludes that this upregulation is positively associated with severe dyskinesias (more upregulation, more dyskinesia).
Some research studies have suggested effects of haloperidol on brain tissue. In a 2005 placebo-compared study of six macaques receiving haloperidol for up to 27 months, a significant brain volume change of about 10% and weight decreases were detected. In later studies (2008) of the stored samples, the previously reported changes were attributed primarily to
astrocyteAstrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...
and
oligodendrocyteOligodendrocytes , or oligodendroglia , are a type of brain cell. They are a variety of neuroglia. Their main function is the insulation of axons in the central nervous system of some vertebrates...
loss, with the neuron loss at about 5%, which was not statistically significant. A study in 2011 of rats given haloperidol in doses comparable to clinical use for 8 weeks found a reduction in brain cortex volume of 10–12%.
In other studies, the use of potent antipsychotics has been associated with cognitive decline and permanent brain damage.
Other remarks
During long-term treatment of chronic psychiatric disorders, it should be tried—in regular intervals—to reduce the daily dose to the lowest level needed for maintenance of remission. Sometimes, it may be indicated to terminate haloperidol treatment gradually.
Other forms of therapy (psychotherapy, occupational therapy/ergotherapie, social rehabilitation) should be instituted properly.
Pregnancy and lactation
Data from
animal experimentsAnimal testing, also known as animal experimentation, animal research, and in vivo testing, is the use of non-human animals in experiments. Worldwide it is estimated that the number of vertebrate animals—from zebrafish to non-human primates—ranges from the tens of millions to more than 100 million...
indicate haloperidol is not teratogenic, but is embryotoxic in high doses. In humans, no controlled studies exist. Unconfirmed studies in pregnant women revealed possible damage to the fetus, although most of the women were exposed to multiple drugs during pregnancy. Following accepted general principles, haloperidol should be given during pregnancy only if the benefit to the mother clearly outweighs the potential fetal risk.
Haloperidol, when given to lactating women, is found in significant amounts in their milk. Breastfed children sometimes show extrapyramidal symptoms. If the use of haloperidol during lactation seems indicated, the benefit for the mother should clearly outweigh the risk for the child. Consider termination of breastfeeding.
Carcinogenicity
In an unconfirmed study at the Buffalo Psychiatric Center, relative risks of breast cancer in inmates undergoing long-term treatment with haloperidol were 3.5 times higher than that of patients at the general hospital, and 9.5 times higher than the reported incidents in the general population. These results need confirmation by larger studies and so far, no statistically acceptable evidence has been found to associate long-term use of haloperidol with the potential for increased breast cancer risk in female patients.
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
Methyldopa is an alpha-adrenergic agonist psychoactive drug used as a sympatholytic or antihypertensive. Its use is now mostly deprecated following the introduction of alternative safer classes of agents...
: increased risk of extrapyramidal side effects and other unwanted central effects
- Levodopa
L-DOPA is a chemical that is made and used as part of the normal biology of some animals and plants. Some animals including humans make it via biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine , and epinephrine collectively...
: 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
Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.-Mechanism:...
, buspironeBuspirone is an anxiolytic psychoactive drug of the azapirone chemical class, and is primarily used to treat generalized anxiety disorder Bristol-Myers Squibb gained FDA approval of buspirone in 1986 for treatment of GAD...
, and fluoxetineFluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
: increased plasma levels of haloperidol, decrease haloperidol dose, if necessary
- Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
, phenobarbitalPhenobarbital or phenobarbitone is a barbiturate, first marketed as Luminal by Friedr. Bayer et comp. It is the most widely used anticonvulsant worldwide, and the oldest still commonly used. It also has sedative and hypnotic properties but, as with other barbiturates, has been superseded by the...
, and rifampicinRifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
: plasma levels of haloperidol significantly decreased, increase haloperidol dose, if necessary
- lithium: rare cases of the following symptoms have been noted: encephalopathy
Encephalopathy means disorder or disease of the brain. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of global brain dysfunction; this syndrome can be caused by many different illnesses.-Terminology:...
, early and late extrapyramidal side effects, other neurologic symptoms, and coma.
- Guanethidine
Guanethidine is an antihypertensive drug that reduces the release of catecholamines, such as norepinephrine. Guanethidine is transported across the sympathetic nerve membrane by the same mechanism that transports norepinephrine itself , and uptake is essential for the drug's action...
: antihypertensive action antagonized
- Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
: 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 10 mg) oral or i.m., usually repeated every 4–6 hours, not exceeding 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 is employed.
- Experimental doses: In resistant cases of psychosis small studies with oral doses of up to 300 mg – 500 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 is recommended to switch the patient gradually to a different neuroleptic (e.g., 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, but are suitable for patients who have demonstrated inconsistency with oral dosages.
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 only certified personnel are legally permitted to administer them to patients.
Symptoms
Symptoms are usually due to exaggerated side effects. Most often encountered are:
- Severe extrapyramidal
Extrapyramidal can refer to:* Extrapyramidal system* Extrapyramidal symptoms...
side effects with muscle rigidity and tremors, akathisiaAkathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
, etc.
- Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
or hypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
- Sedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...
- Anticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
side effects (dry mouth, constipation, paralytic ileusIleus is a disruption of the normal propulsive ability of the gastrointestinal tract.Ileus is commonly defined simply as bowel obstruction. However, authoritative sources define it as decreased motor activity of the GI tract due to non-mechanical causes...
, difficulties in urinating, massive sweating)
- Coma in severe cases, accompanied by respiratory depression and massive hypotension, shock
- Rarely, serious ventricular arrhythmia (torsades de pointes
Torsades de pointes, or simply torsades, is a French term that literally means "twisting of the points". It was first described by Dessertenne in 1966 and refers to a specific, rare variety of ventricular tachycardia that exhibits distinct characteristics on the electrocardiogram .- Presentation...
), with or without prolonged QT-time
- Epileptic seizures.
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 lavageGastric lavage, also commonly called stomach pumping or Gastric irrigation, is the process of cleaning out the contents of the stomach. It has been used for over 200 years as a means of eliminating poisons from the stomach. Such devices are normally used on a person who has ingested a poison or...
, and the use of activated charcoal can all be tried. Avoid
epinephrineEpinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
for treatment of hypotension and shock, because its action might be reversed.
Prognosis
In general, the prognosis of overdose is good and lasting damage is not 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 often used in people known to be noncompliant with oral medication. 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, e.g., a parrot that will otherwise continuously pluck 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 brand Haldol and many generics are available
External links