Pimozide (sold under the brand name Orap) is an

antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of ...

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhala ...

of the diphenylbutylpiperidine class. It was discovered at

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 ...

in 1963. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weight basis it is even more potent than haloperidol. It also has special neurologic indications for Tourette syndrome and resistant tics. The side effects include akathisia, tardive dyskinesia, and, more rarely, neuroleptic malignant syndrome and prolongation of the

QT interval 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 ...

Medical uses

Pimozide is used in its oral preparation in

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 w ...

and chronic

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 behavi ...

(on-label indications in Europe only), Tourette syndrome, and resistant tics (Europe, United States and Canada). There have been numerous studies showing Pimozide can be used successfully to treat

Delusional parasitosis Delusional parasitosis (DP) is a mental disorder in which individuals have a persistent belief that they are infested with living or nonliving pathogens such as parasites, insects, or bugs, when no such infestation is present. They usually report ...

and traditionally was the drug of choice. However, newer medications have become prevalent recently as the preferred medication. In one case a series of 33 patients with delusional parasitosis (median age, 60 years), pimozide was prescribed for 24 patients, 18 of whom took the drug. The dose ranged from 1 to 5 mg daily. No information regarding initial dosing was specified, although the dose was continued for 6 weeks prior to tapering. Of those patients receiving pimozide, 61% (11/18) experienced improvement in or full remission of symptoms. The use of pimozide for the treatment of delusional parasitosis is based primarily on data from case series/reports that demonstrate some efficacy in the majority of patients. Currently, atypical antipsychotics such as olanzapine or risperidone are used as first line treatment. However, patients who experience negative side-effects with the first line medications are typically given pimozide. Pimozide has been used in the treatment of

delusional disorder Delusional disorder is a mental illness in which a person has delusions, but with no accompanying prominent hallucinations, thought disorder, mood disorder, or significant flattening of affect.American Psychiatric Association. (2013). ''Diagnostic ...

and paranoid personality disorder.

Efficacy

A 2013

systematic review A systematic review is a 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 published studies on t ...

compared pimozide with other antipsychotics for schizophrenia or related psychoses:

Contraindications

It is contraindicated in individuals with either acquired, congenital or a family history of QT interval prolongation. Its use is advised against in individuals with people with either a personal or a family history of arrhythmias or

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 ...

. Likewise its use is also advised against in individuals with uncorrected

hypokalaemia 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 abnorm ...

and hypomagnesaemia or clinical significant cardiac disorders (e.g. a recent

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...

bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, ...

. It is also contraindicated in individuals being cotreated with

SSRIs Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellu ...

or in those with a known hypersensitivity to pimozide or other diphenylbutyl-piperidine derivatives. Likewise its use is contraindicated in individuals receiving treatment with

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 ...

, CYP1A2, or CYP2D6 inhibitors.

Side effects

Very common (>10% frequency) side effects include: * Akinesia * Constipation * Dizziness * Dry mouth *

Hyperhidrosis Hyperhidrosis is a condition characterized by abnormally increased sweating, in excess of that required for regulation of body temperature. Although primarily a benign physical burden, hyperhidrosis can deteriorate quality of life from a psychologi ...

Nocturia Nocturia is defined by the International Continence Society (ICS) as “the complaint that the individual has to wake at night one or more times for voiding (''i.e. to urinate'').” The term is derived from Latin ''nox, night'', and Greek '' �α ...

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 ...

* Speech disorder

Overdose

Pimozide overdose presents with severe extrapyramidal symptoms,

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 di ...

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, ...

, QT interval prolongation and ventricular arrhythmias including

. Gastric lavage, establishment of a patent airway and, if necessary, mechanically assisted respiration is the recommended treatment for pimozide overdose. Cardiac monitoring should be continued for at least 4 days due to the long half-life of pimozide.

Pharmacology

Pimozide acts as an

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...

of the D₂, D₃, and D₄ receptors and the 5-HT₇ receptor. It is also a

hERG hERG (the human '' Ether-à-go-go''-Related Gene) is a gene () that codes for a protein known as Kv11.1, the alpha subunit of a potassium ion channel. This ion channel (sometimes simply denoted as 'hERG') is best known for its contribution to t ...

blocker. Similarly to other typical antipsychotics pimozide has a high affinity for the Dopamine D₂ receptor and this likely results in its sexual (due to prolactin hypersecretion) and extrapyramidal side effects as well as its therapeutic efficacy against the positive symptoms of

History

In 1985 the pimozide was approved by the FDA for marketing as an

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

for the treatment of Tourette's syndrome.

Notes

References

External links

{{authority control 1-(4,4-Bis(4-fluorophenyl)butyl)piperidines 5-HT7 antagonists Belgian inventions Benzimidazoles D2 antagonists D3 antagonists D4 antagonists Delusional parasitosis Imidazolidinones Janssen Pharmaceutica Orphan drugs Potassium channel blockers Typical antipsychotics