Haloperidol, sold under the brand name Haldol among others, is a
typical antipsychotic
Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics ma ...
medication.
Haloperidol is used in the treatment of
schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
, tics in
Tourette syndrome
Tourette syndrome or Tourette's syndrome (abbreviated as TS or Tourette's) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) ...
,
mania
Mania, also known as manic syndrome, is a mental and behavioral disorder defined as a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together wit ...
in
bipolar disorder
Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
,
delirium
Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances in ...
, agitation, acute
psychosis
Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...
, and
hallucinations
A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinatio ...
from
alcohol withdrawal
Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in alcohol use after a period of excessive use. Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, and a mild fever. M ...
.
It may be used by mouth or injection into a
muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
or a
vein
Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated b ...
.
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.
Haloperidol may result in a movement disorder known as
tardive dyskinesia
Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movemen ...
which may be permanent.
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fas ...
and
QT interval prolongation may occur.
In older people with psychosis due to
dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
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
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
.
Haloperidol was discovered in 1958 by
Paul Janssen
Paul Adriaan Jan, Baron Janssen (12 September 1926 - 11 November 2003) was a Belgian physician. He was the founder of Janssen Pharmaceutica, a pharmaceutical company with over 20,000 employees which is now a subsidiary of Johnson & Johnson.
Ea ...
, prepared as part of a
structure-activity relationship investigation into analogs of
pethidine
Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a synthetic opioid analgesic, pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemis ...
(meperidine). It is on the
World Health Organization's List of Essential Medicines
The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...
.
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 1million 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
Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...
, such as drug-induced psychosis caused by, amphetamines,
ketamine
Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ne ...
, and
phencyclidine
Phencyclidine or phenylcyclohexyl piperidine (PCP), also known as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. PCP may cause hallucinations, distorted perceptio ...
, 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
Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in alcohol use after a period of excessive use. Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, and a mild fever. M ...
* Hyperactive
delirium
Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances in ...
(to control the agitation component of delirium)
*
Hyperactivity
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...
,
aggression
Aggression is overt or covert, often harmful, social interaction with the intention of inflicting damage or other harm upon another individual; although it can be channeled into creative and practical outlets for some. It may occur either reacti ...
* Otherwise uncontrollable, severe behavioral disorders in children and adolescents
*
Schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
* Therapeutic trial in
personality disorders
Personality disorders (PD) are a class of mental disorders characterized by enduring maladaptive patterns of behavior, cognition, and inner experience, exhibited across many contexts and deviating from those accepted by the individual's culture ...
, such as
borderline personality disorder
Borderline personality disorder (BPD), also known as emotionally unstable personality disorder (EUPD), is a personality disorder characterized by a long-term pattern of unstable interpersonal relationships, distorted sense of self, and strong ...
* Treatment of intractable
hiccups
A hiccup (scientific name ''singultus'', from a Latin word meaning "to catch one's breath while sobbing"; also spelled hiccough) is an involuntary contraction (myoclonic jerk) of the diaphragm that may repeat several times per minute. The hic ...
* Treatment of neurological disorders, such as
tic disorder
Tic disorders are defined in the ''Diagnostic and Statistical Manual of Mental Disorders'' (DSM) based on type (motor or phonic) and duration of tics (sudden, rapid, nonrhythmic movements). Tic disorders are defined similarly by the World Health ...
s such as
Tourette syndrome
Tourette syndrome or Tourette's syndrome (abbreviated as TS or Tourette's) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) ...
, and
chorea
Chorea (or choreia, occasionally) is an abnormal involuntary movement disorder, one of a group of neurological disorders called dyskinesias. The term ''chorea'' is derived from the grc, χορεία ("dance"; see choreia), as the quick movement ...
* Treatment of severe nausea and emesis in postoperative and
palliative care
Palliative care (derived from the Latin root , or 'to cloak') is an interdisciplinary medical caregiving approach aimed at optimizing quality of life and mitigating suffering among people with serious, complex, and often terminal illnesses. Wit ...
, especially for palliating adverse effects of
radiation therapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
and
chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
in
oncology
Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ó ...
. 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
Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The IM form may be used for acute agitation ...
,
chlorpromazine
Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar dis ...
, and
asenapine
Asenapine, sold under the brand name Saphris among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder.
It was chemically derived via altering the chemical structure of the ...
, approximately as effective as
quetiapine
Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its ...
and
aripiprazole
Aripiprazole, sold under the brand names Abilify and Aristada among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder. Other uses include as an add-on treatment in major depressiv ...
, and 10% less effective than
paliperidone
Paliperidone, sold under the trade name Invega among others, is an atypical antipsychotic. It is mainly used to treat schizophrenia and schizoaffective disorder.
It is marketed by Janssen Pharmaceuticals. An extended release formulation is a ...
.
A 2013
systematic review
A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
compared haloperidol to
placebo
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures.
In general ...
in schizophrenia:
Pregnancy and lactation
Data from
animal experiments indicate haloperidol is not
teratogenic
Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The related t ...
, but is
embryotoxic
Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The related t ...
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
An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...
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
![Haloperidol decanoate highlighting ester group](https://upload.wikimedia.org/wikipedia/commons/1/1e/Haloperidol_decanoate_highlighting_ester_group.svg)
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
Capric acid, also known as decanoic acid or decylic acid, is a saturated fatty acid, medium-chain fatty acid (MCFA), and carboxylic acid. Its formula is CH3(CH2)8COOH. Salts and esters of decanoic acid are called caprates or decanoates. The ter ...
ester of haloperidol (
haloperidol decanoate
Haloperidol decanoate, sold under the brand name Haldol Decanoate among others, is a typical antipsychotic which is used in the treatment of schizophrenia. It is administered by injection into muscle at a dose of 100 to 200 mg once every 4& ...
, trade names Haldol decanoate, Halomonth, Neoperidole) has a much longer
duration of action
Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (for ...
, 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
In chemical nomenclature, a preferred IUPAC name (PIN) is a unique name, assigned to a chemical substance and preferred among the possible names generated by IUPAC nomenclature. The "preferred IUPAC nomenclature" provides a set of rules for cho ...
of haloperidol decanoate is
-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyliperidin-4-yl.html" ;"title="-(4-fluorophenyl)-4-oxobutyl.html" ;"title="-(4-chlorophenyl)-1-
-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyliperidin-4-yl">-(4-fluorophenyl)-4-oxobutyl.html"_;"title="-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl">-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyliperidin-4-yldecanoate.
Topical_medication.html" ;"title="-(4-fluorophenyl)-4-oxobutyl">-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyliperidin-4-yl">-(4-fluorophenyl)-4-oxobutyl.html" ;"title="-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl">-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyliperidin-4-yldecanoate.
Topical medication">Topical formulations of haloperidol should not be used as treatment for nausea because research does not indicate this therapy is more effective than alternatives.
[, which cites
*
* ]
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
Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back and ...
(motor restlessness)
** Dystonia
Dystonia is a neurological hyperkinetic movement disorder in which sustained or repetitive muscle contractions result in twisting and repetitive movements or abnormal fixed postures. The movements may resemble a tremor. Dystonia is often inten ...
(continuous spasms and muscle contractions)
** Muscle rigidity
** Parkinsonism
Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability. These are the four motor symptoms found in Parkinson's disease (PD), after which it is named, dementia with Lewy bo ...
(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
Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
(which is not a particularly prominent side effect, as is supported by the results of the aforementioned meta-analysis.[)
Unknown frequency
* ]Anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
* Headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
* Increased respiratory rate
* Orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...
* Prolonged QT interval
* Visual disturbances
Rare (<1% incidence)
* Acute hepatic failure
* Agitation
* Agranulocytosis
Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing a neutropenia in the circulating blood. ...
* Anaphylactic reaction
Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...
* Anorexia
* Bronchospasm
* Cataracts
* Cholestasis
Cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system that can occur from a gallstone or malignan ...
* Confusional state
* Depression
* Dermatitis exfoliative
* Dyspnea
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathing, breathe well enough. The American Thoracic Society defines it as "a subjective experience of brea ...
* Edema
* Extrasystole
A premature heart beat or extrasystole is a heart rhythm disorder corresponding to a premature contraction of one of the chambers of the heart. Premature heart beats come in two different types: premature atrial contractions and premature vent ...
s
* Face edema
* Gynecomastia
Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (1 ...
* Hepatitis
Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...
* Hyperglycemia
* Hypersensitivity
* Hyperthermia
* Hypoglycemia
* Hyponatremia
Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be abs ...
* Hypothermia
* Increased sweating
* Injection site abscess
* Insomnia
* Itchiness
* Jaundice
* Laryngeal edema
* Laryngospasm
Laryngospasm is an uncontrolled or involuntary muscular contraction (spasm) of the vocal folds. The condition typically lasts less than 60 seconds, but in cases partial blocking it may last 20 to 30 minutes and hinder inspiration, while exhala ...
* Leukocytoclastic vasculitis
* Leukopenia
Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of inf ...
* Liver function test abnormal
* Nausea
* Neuroleptic malignant syndrome
Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fas ...
* Neutropenia
Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria ...
* Pancytopenia
Pancytopenia is a medical condition in which there is significant reduction in the number of almost all blood cells (red blood cells, white blood cells, platelets, monocytes, lymphocytes, etc.).
If only two parameters from the complete blood coun ...
* Photosensitivity reaction
* Priapism
Priapism is a condition in which a penis remains erect for hours in the absence of stimulation or after stimulation has ended. There are three types: ischemic (low-flow), nonischemic (high-flow), and recurrent ischemic (intermittent). Most cases ...
* Psychotic disorder
Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior t ...
* Pulmonary embolism
* Rash
* Retinopathy
Retinopathy is any damage to the retina of the eyes, which may cause vision impairment. Retinopathy often refers to retinal vascular disease, or damage to the retina caused by abnormal blood flow. Age-related macular degeneration is technically inc ...
* Seizure
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
* Sudden death
* Tardive dyskinesia
Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movemen ...
* Thrombocytopenia
Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...
* Torsades de pointes
''Torsades de pointes, torsade de pointes'' or ''torsades des pointes'' (TdP) (, , translated as "twisting of peaks") is a specific type of abnormal heart rhythm that can lead to sudden cardiac death. It is a polymorphic ventricular tachycardia t ...
* Urinary retention
* Urticaria
Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...
* Ventricular fibrillation
Ventricular fibrillation (V-fib or VF) is an abnormal heart rhythm in which the ventricles of the heart quiver. It is due to disorganized electrical activity. Ventricular fibrillation results in cardiac arrest with loss of consciousness and no p ...
* Ventricular tachycardia
Ventricular tachycardia (V-tach or VT) is a fast heart rate arising from the lower chambers of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple episodes over a short period ...
* Vomiting
Contraindications
* Pre-existing coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
, 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
In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears on the package insert for certain prescription drugs, so called because
the U.S. Food and Drug Administration specifies that it ...
about this risk.
* Impaired liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
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
Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainting, ...
(hypokalemia
Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...
, concomitant use of other drugs causing QT prolongation)
* Patients with a history of leukopenia: a complete blood count
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cell ...
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
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
or dementia with Lewy bodies
Dementia with Lewy bodies (DLB) is a type of dementia characterized by changes in sleep, behavior, cognition, movement, and regulation of automatic bodily functions. Memory loss is not always an early symptom. The disease worsens over time ...
Interactions
* Amiodarone
Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as atrial fibrilla ...
: Q-Tc interval prolongation (potentially dangerous change in heart rhythm).
* Amphetamine
Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
and methylphenidate
Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, ...
: counteracts increased action of norepinephrine and dopamine in patients with narcolepsy
Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...
or ADD
Addition (usually signified by the plus symbol ) is one of the four basic operations of arithmetic, the other three being subtraction, multiplication and division. The addition of two whole numbers results in the total amount or '' sum'' of ...
/ADHD
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...
* Epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
: action antagonized, paradoxical decrease in blood pressure may result
* 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 (NET, upta ...
: antihypertensive action antagonized
* Levodopa
-DOPA, also known as levodopa and -3,4-dihydroxyphenylalanine, is an amino acid that is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DOPA ...
: decreased action of levodopa
* Lithium
Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid el ...
: rare cases of the following symptoms have been noted: encephalopathy
Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but r ...
, early and late extrapyramidal side effects, other neurologic symptoms, and coma.
* Methyldopa
Methyldopa, sold under the brand name Aldomet among others, is a medication used for high blood pressure. It is one of the preferred treatments for high blood pressure in pregnancy. For other types of high blood pressure including hypertensive e ...
: 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
Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medi ...
, phenobarbital
Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ep ...
, and rifampicin
Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), mycobacterium avium complex, ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. ...
decrease plasma levels and inhibitors such as quinidine
Quinidine is a class I antiarrhythmic agent, class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is the enantiomer of Antimalarial medication, antimalarial agent quinine, originally derived from the bark of the cinchona tre ...
, buspirone
Buspirone, sold under the brand name Buspar, among others, is a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder. Benefits support its short-term use. It is taken by mouth, and it may take up to fo ...
, and fluoxetine
Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorde ...
increase plasma levels
* Tricyclic antidepressants
Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
: metabolism and elimination of tricyclics significantly decreased, increased toxicity noted (anticholinergic and cardiovascular side effects, lowering of seizure threshold)
Discontinuation
The British National Formulary
The ''British National Formulary'' (BNF) is a United Kingdom (UK) pharmaceutical reference book that contains a wide spectrum of information and advice on prescribing and pharmacology, along with specific facts and details about many medicines ...
recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping.[ Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.][ Symptoms generally resolve after a short period of time.][
There is tentative evidence that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped.][
]
Overdose
Symptoms
Symptoms are usually due to side effects. Most often encountered are:
* Anticholinergic
Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system.
These agents inhibit the parasympathetic nervous system ...
side effects (dry mouth, constipation, paralytic ileus
Ileus is a disruption of the normal propulsive ability of the intestine. It can be caused by lack of peristalsis or by mechanical obstruction.
The word 'ileus' is from Ancient Greek ''eileós'' (, "intestinal obstruction"). The term 'subileus' re ...
, difficulties in urinating, decreased perspiration
Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals.
Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distrib ...
)
* Coma in severe cases, accompanied by respiratory depression and massive hypotension, shock
* Hypotension
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...
or hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
* Rarely, serious ventricular arrhythmia (''torsades de pointes''), with or without prolonged QT-time
The QT interval is a measurement made on an electrocardiogram used to assess some of the electrical properties of the heart. It is calculated as the time from the start of the Q wave to the end of the T wave, and approximates to the time taken ...
* Sedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...
* Severe extrapyramidal side effects with muscle rigidity and tremors, akathisia
Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back and ...
, etc.
Treatment
Treatment is mostly symptomatic and involves intensive care with stabilization of vital functions. In early detected cases of oral overdose, induction of emesis
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteriti ...
, gastric lavage
Gastric lavage, also commonly called stomach pumping or gastric irrigation, is the process of cleaning out the contents of the stomach. Since its first recorded use in early 19th century, it has become one of the most routine means of eliminating ...
, and the use of activated charcoal
"Activated" is a song by English singer Cher Lloyd. It was released on 22 July 2016 through Vixen Records. The song was made available to stream exclusively on ''Rolling Stone'' a day before to release (on 21 July 2016).
Background
In an interv ...
can be tried. In the case of a severe overdose, antidotes such as bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic maligna ...
or ropinirole
Ropinirole, sold under the brand name Requip among others, is a medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). In PD the dose needs to be adjusted to the effect and treatment should not be suddenly stopped. ...
may be used to treat the extrapyramidal effects caused by haloperidol, acting as dopamine receptor agonists. ECG and vital signs should be monitored especially for QT prolongation and severe arrhythmias should be treated with antiarrhythmic measures.
Prognosis
An overdose of haloperidol can be fatal, but in general the prognosis after overdose is good, provided the person has survived the initial phase.
Pharmacology
Haloperidol is a typical butyrophenone
Butyrophenone is an organic compound with the formula C6H5C(O)C3H7. It is a colorless liquid.
The butyrophenone structure—a ketone flanked by a phenyl ring and a butyl chain—forms the basis for many other chemicals containing various sub ...
type antipsychotic that exhibits high affinity dopamine D2 receptor antagonism and slow receptor dissociation kinetics. It has effects
Effect may refer to:
* A result or change of something
** List of effects
** Cause and effect, an idiom describing causality
Pharmacy and pharmacology
* Drug effect, a change resulting from the administration of a drug
** Therapeutic effect, a ...
similar to the phenothiazine
Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. T ...
s. 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. 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
Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...
though having higher rates of treatment emergent extrapyramidal symptom
Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side ...
s.
Haloperidol acts on these receptors: ( Ki)
* D1 (silent antagonist
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of recep ...
) – Unknown efficiency
* D5 (silent antagonist) – Unknown efficiency
* D2 (inverse agonist
In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist.
A neutral antagonist has no activity in the absence of an agonist or inverse agon ...
) – 0.7 nM
* D3 (inverse agonist) – 0.2 nM
* D4 (inverse agonist) – 5–9 nM
* σ1 (irreversible inactivation by haloperidol metabolite HPP+) – 3 nM
* σ2 (agonist): 54 nM
* 5HT1A receptor agonist – 1927 nM
* 5HT2A (silent antagonist) – 53 nM
* 5HT2C (silent antagonist) – 10,000 nM
* 5HT6 (silent antagonist) – 3666 nM
* 5HT7 (irreversible silent antagonist) – 377.2 nM
* H1 (silent antagonist) – 1,800 nM
* M1 (silent antagonist) – 10,000 nM
* α1A (silent antagonist) – 12 nM
* α2A (silent antagonist) – 1130 nM
* α2B (silent antagonist) – 480 nM
* α2C (silent antagonist) – 550 nM
* NR1/NR2B subunit containing NMDA receptor
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA rece ...
(antagonist; ifenprodil
Ifenprodil is an inhibitor of the NMDA receptor, specifically of GluN1 (glycine-binding NMDA receptor subunit 1) and GluN2B (glutamate-binding NMDA receptor subunit 2) subunits. Additionally, ifenprodil inhibits GIRK channels, and interacts with a ...
site): IC50 – 2,000 nM
Pharmacokinetics
By mouth
The bioavailability of oral haloperidol ranges from 60 to 70%. However, there is a wide variance in reported mean Tmax and T1/2 in different studies, ranging from 1.7 to 6.1 hours and 14.5 to 36.7 hours respectively.
Intramuscular injections
The drug is well and rapidly absorbed with a high bioavailability when injected intramuscularly. The Tmax is 20 minutes in healthy individuals and 33.8 minutes in patients with schizophrenia. The mean T1/2 is 20.7 hours. The decanoate
Capric acid, also known as decanoic acid or decylic acid, is a saturated fatty acid, medium-chain fatty acid (MCFA), and carboxylic acid. Its formula is CH3(CH2)8COOH. Salts and esters of decanoic acid are called caprates or decanoates. The ter ...
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 six days after the injection, falling thereafter, with an approximate half-life of three weeks.
Intravenous injections
The bioavailability is 100% in intravenous (IV) injection, and the very rapid onset of action is seen within seconds. The T1/2 is 14.1 to 26.2 hours. The apparent volume of distribution is between 9.5 and 21.7 L/kg. The duration of action is four to six hours.
Therapeutic concentrations
Plasma levels of five to 15 micrograms per liter are typically seen for therapeutic response (Ulrich S, et al. Clin Pharmacokinet. 1998). The determination of plasma levels is rarely used to calculate dose adjustments but can be useful to check compliance.
The concentration of haloperidol in brain tissue is about 20-fold higher compared to blood levels. It is slowly eliminated from brain tissue, which may explain the slow disappearance of side effects when the medication is stopped.
Distribution and metabolism
Haloperidol is heavily protein bound in human plasma, with a free fraction of only 7.5 to 11.6%. It is also extensively metabolized in the liver with only about 1% of the administered dose excreted unchanged in the urine. The greatest proportion of the hepatic clearance is by glucuronidation, followed by reduction and CYP-mediated oxidation, primarily by CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
.
History
Haloperidol was discovered by Paul Janssen
Paul Adriaan Jan, Baron Janssen (12 September 1926 - 11 November 2003) was a Belgian physician. He was the founder of Janssen Pharmaceutica, a pharmaceutical company with over 20,000 employees which is now a subsidiary of Johnson & Johnson.
Ea ...
. It was developed in 1958 at the Belgian company Janssen Pharmaceutica
Janssen Pharmaceuticals is a pharmaceutical company headquartered in Beerse, Belgium, and wholly-owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen.
In 1961, Janssen Pharmaceuticals was purchased by New Jersey-based American ...
and submitted to the first of clinical trials in Belgium
Belgium, ; french: Belgique ; german: Belgien officially the Kingdom of Belgium, is a country in Northwestern Europe. The country is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeast, France to th ...
later that year.
Haloperidol was approved by the U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) on 12 April 1967; it was later marketed in the U.S. and other countries under the brand name Haldol by McNeil Laboratories
McNeil Consumer Healthcare is an American medicals products company belonging to the Johnson & Johnson healthcare products group. It primarily sells fast-moving consumer goods such as over-the-counter drugs.
History
The company was founded on M ...
.
Society and culture
Cost
Haloperidol is relatively inexpensive, being up to 100 fold less expensive than newer antipsychotics.
Brand names
Haloperidol is the INN
Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...
, BAN, USAN
280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk(于山國)was Ulleungdo(鬱陵島)
Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms period. According to th ...
, AAN
''Aan'' (Hindi: आन, Urdu: آن, translation: ''Pride''), released as ''The Savage Princess'' in the United Kingdom and United States, is a 1952 Indian Bollywood adventure film, produced and directed by Mehboob Khan. It was India's first t ...
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 and Sigaperidol.
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.
References
External links
*
{{Authority control
4-Phenylpiperidines
4-Hydroxypiperidines
Antiemetics
Belgian inventions
Butyrophenone antipsychotics
Chemical substances for emergency medicine
Chloroarenes
CYP2D6 inducers
CYP2D6 inhibitors
Fluoroarenes
Johnson & Johnson brands
Janssen Pharmaceutica
NMDA receptor antagonists
Prolactin releasers
Suspected embryotoxicants
Suspected fetotoxicants
Tertiary alcohols
Typical antipsychotics
World Health Organization essential medicines
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