Pimozide (Orap®)

This article provides an overview of pimozide, including its uses, how it works, and important information on precautions, side effects, and drug interactions.

Key Takeaways:

• Pimozide is a type of antipsychotic medication. It blocks dopamine receptors in the brain, which leads to reduced effects of dopamine and other effects in the central nervous system.

• Pimozide is most often used to manage severe tics within Tourette’s syndrome. It is also used for managing schizophrenia and other forms of psychosis, particularly after other medications have been tried.

• Pimozide has many possible side effects and interactions, some of which are severe and life-threatening (e.g., heart rhythm abnormalities, extrapyramidal symptoms, nervous system depression). Your doctor can help determine if pimozide is right for you and what your best treatment plan looks like.

Understanding Pimozide

Pimozide is a first-generation (or typical) antipsychotic. It was first approved for use in the US in 1984 for Tourette's syndrome, but has been used historically off-label in the US and in other countries to treat schizophrenia and other psychotic disorders. Today, it isn’t used as often for those conditions, being largely replaced by newer, atypical antipsychotics that typically have fewer side effects. One of the main uses of pimozide today is for managing severe tics in Tourette’s syndrome. ^[1]

How Does Pimozide Work?

Pimozide belongs to a class of drugs called dopamine receptor antagonists, which means it blocks dopamine receptors and, therefore, inhibits the effects of dopamine in the nervous system. It also has anticholinergic and alpha-adrenergic blockade effects, which reduce the effects of acetylcholine and adrenaline, respectively. ^{[1] [2]}

Among these, it is believed that the dopamine-blocking actions of pimozide are primarily responsible for the reduction in tics, as well as the decreased symptoms of psychosis, such as delusions and hallucinations. ^{[1] [2]}

Brand Names

Pimozide used to be sold under the brand name Orap®, but it is discontinued. Prescriptions for generic pimozide are still available.

What is Pimozide Used For

Pimozide is FDA-approved to manage severe motor and verbal tics that occur in individuals with Tourette’s syndrome. It is only used after other treatments have failed. This is the only approved indication for pimozide in the United States. ^[1]

Off-Label Uses

Pimozide is also used off-label for schizophrenia and treatment-resistant psychosis, although typically only after other medications have been tried. Within treatment-resistant psychosis, pimozide may be combined with other medications, such as clozapine. ^{[2] [3]}

Pimozide is also sometimes used in cases of autism spectrum disorder (ASD).

Pimozide Side Effects

There are several possible side effects of pimozide. It is one of the antipsychotics that’s most likely to cause extrapyramidal symptoms, which refers to a group of neuromuscular reactions that may involve: ^{[2] [3]}

• Shuffling or slow walk

• Rigidity

• Tremors

• Stiff muscles

• Trouble swallowing

• Difficulty speaking

• Muscle spasms or cramps

• Mask-like facial expression

• Drooling

Other common side effects of pimozide include: ^{[1] [3] [4] [5]}

• Drowsiness

• Weight changes

• Dry mouth

• Blurred vision

• Constipation

• Changes in the menstrual cycle

• Decreased sexual function

• Decreased libido

• Breast swelling and milk production (can be in both women and men)

• Nausea

• Insomnia

Due to its effects on dopamine, pimozide may also cause various mood and mental side effects, such as depression, low mood, decreased motivation, dissatisfaction, lack of interest or enjoyment, and indifference. ^[4]

Rare and Severe Side Effects

There are also several less common side effects with Pimozide. While rare, some of these are severe and may require immediate medical attention. They include: ^{[2] [4] [5]}

• QT Prolongation: This prolongs the QT interval in the heart’s natural rhythm, which can lead to seizures or even death in serious cases.

• Agranulocytosis: A severe and dangerous decreased white blood cell count

• Anaphylactic reaction: A severe allergic reaction

• Neuroleptic malignant syndrome (NMS): NMS can cause a range of symptoms, including significantly altered mental status, muscle rigidity, high fever, rapid heart rate and breathing, and sweating.

Individuals taking pimozide are also at a greater risk of sudden death compared to those not taking the medication. ^[1]

Pimozide Dosage

Pimozide dosage requires careful monitoring due to the possibility of significantly increased side effects at even minor increases in dosing. Individuals are typically prescribed one of the smallest doses initially, followed by a slow, gradual increase until the most effective dose is achieved, while still maintaining a safe side effect profile. ^[2]

While not typically recommended due to limited data in children, the recommended dose starts at 0.05mg/kg, which can be increased to 0.2mg/kg, but not over 10mg total. It is taken once daily for the management of tics. ^[2]

In adults, most are started out on a dose of 1 to 2mg per day, typically with a maximum dose per day of 10mg. Doses above 10mg are not recommended. ^[2]

General dosage guidelines are 1 to 10mg per day for Tourette syndrome, and 2 to 12mg per day for schizophrenia and other psychotic illnesses. ^{[3] [4]}

Methods of Administration

Pimozide is administered orally. It is available in 1mg and 2mg oral tablets. ^{[4] [5]}

Precautions

There are several important precautions to be aware of with pimozide. For example, pimozide may be unsafe or pose an increased risk of side effects for individuals with the following conditions: ^{[2] [5]}

• Low white blood cell count: Increases the risk of agranulocytosis and related issues with low white blood cell counts

• Liver or kidney impairments: May reduce drug clearance ability, which could lead to greater effects of the drug in the body

• Heart arrhythmias or other cardiovascular issues: increase the risk of QT prolongation and sudden death

• Central nervous system (CNS) depression

• Tics not caused by Tourette’s syndrome

• History of seizures

• Breast cancer

• Parkinson’s disease

Pimozide may cause drowsiness and mental and/or physical impairments, which may make it unsafe to drive, operate machinery, or perform other complex tasks. This is especially true in the first few days of using it. ^[2]

Pimozide may also cause adverse effects on birth, growth, and development. So, it should be used very cautiously in pregnant and nursing women. ^[2]

Harmful Interactions

Pimozide may cause harmful interactions with many different substances, including certain prescription medications, over-the-counter drugs and supplements, and alcohol.

Pimozide should not be used with other drugs that may prolong the QT interval. This increases the risk of heart rhythm abnormalities. There are many, but examples include: ^{[2] [4]}

• Tricyclic antidepressants (e.g. amitriptyline, desipramine)

• Antiarrhythmic medications (e.g. amiodarone)

• Phenothiazines

Pimozide may also enhance the effects of CNS depressants, such as:

• Analgesics

• Sedatives

• Anxiolytics

• Alcohol

Taking pimozide alongside the above substances may lead to an increased risk of drowsiness, sedation, and impaired motor and cognitive functioning, which may also increase the risk of falls, accidents, and injuries. In severe instances, this combination can also result in slowed or shallow breathing.

Pimozide is contraindicated and should not be taken with selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, paroxetine, and sertraline. ^{[2] [4]}

Additionally, you should avoid consuming grapefruit or grapefruit juice while taking pimozide. This can lead to greater concentrations of pimozide in the body. ^[2]

Lastly, pimozide may interact with several other types of medications, such as:

• Antifungals

• Protease inhibitor drugs

Safe Storage

It’s important to keep pimozide in its original container, tightly closed, and away from children. Store it at room temperature and away from excess heat and moisture.

Final Thoughts

Pimozide offers potential benefits for individuals suffering with severe tics within Tourette’s syndrome, and may also be effective in certain cases of schizophrenia and psychosis. However, it is often not the first medication of choice for these issues, in part due to its relatively high risk of side effects and interactions. Talk to your doctor to see if pimozide may be right for you. They’ll be able to provide the safest and most effective individualized treatment plan for your needs.