Paliperidone, sold under the brand name Invega among others, is an atypical antipsychotic. It is used for the treatment of

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

and schizoaffective disorder. It is marketed by Janssen Pharmaceuticals. Paliperidone was approved by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) for the treatment of schizophrenia in December 2006, and in the European Union in June 2007. Paliperidone palmitate is a long-acting injectable formulation of paliperidone palmitoyl

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

. 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 s ...

. Paliperidone is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

Medical use

In the United States, paliperidone is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of schizophrenia and for the treatment of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers and/or antidepressants. In the European Union, paliperidone is indicated for the treatment of schizophrenia in adults and in adolescents fifteen years of age and older and for the treatment of schizoaffective disorder in adults. Paliperidone is used for the treatment of

and schizoaffective disorder.

Adverse effects

The most common side effects include headache,

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

, sleepiness,

parkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), Rigidity (neurology), rigidity, and balance disorder, postural instability. Both hypokinetic features (bradykinesia and akinesia) and hyperkinetic f ...

(effects similar to Parkinson's disease such as shaking, muscle stiffness and slow movement),

dystonia Dystonia is a neurology, neurological Hyperkinesia, hyperkinetic Movement disorders, movement disorder in which sustained or repetitive muscle contractions occur involuntarily, resulting in twisting and repetitive movements or abnormal fixed po ...

(involuntary muscle contractions),

tremor A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...

(shaking), dizziness,

akathisia Akathisia (IPA: /æ.kə.ˈθɪ.si.ə/) is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and/or an inability to sit still. Usually, the legs are most prominently affected. Those a ...

(restlessness), agitation, anxiety, depression, increased weight, nausea, vomiting, constipation, dyspepsia (heartburn), diarrhea, dry mouth, tiredness, toothache, muscle and bone pain, back pain, asthenia (weakness),

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

(increased heart rate), high blood pressure, prolonged QT interval (an alteration of the electrical activity of the heart),

upper respiratory tract infection An upper respiratory tract infection (URTI) is an illness caused by an acute infection, which involves the upper respiratory tract, including the nose, sinuses, pharynx, larynx or trachea. This commonly includes nasal obstruction, sore throat ...

(nose and throat infections) and cough. A 2023 study found that paliperidone may worsen verbal learning and memory compared to

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

in the early months of psychosis treatment. 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.

Pharmacology

Paliperidone is the primary active metabolite of the older antipsychotic

risperidone Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder, as well as aggressive and self-injurious behaviors associated with autism spectrum disorder. It is t ...

. While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways. Its efficacy is believed to result from central

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic pathways, Dopaminergic brain pathways facil ...

and serotonergic antagonism except paliperidone, like its parent compound risperidone, functions as an inverse agonist at 5-HT2
15
Paliperidone also acts as an antagonist of alpha-1 and alpha-2 adrenergic receptors as well as H1 histaminergic receptors. Food is known to increase the absorption of Invega type ER OROS prolonged-release tablets. Food increased exposure of paliperidone by up to 50-60%; however, half-life was not significantly affected. The effect was probably due to a delay in the transit of the ER OROS formulation in the upper part of the GI tract, resulting in increased absorption.

Risperidone Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder, as well as aggressive and self-injurious behaviors associated with autism spectrum disorder. It is t ...

and its metabolite paliperidone are reduced in efficacy by P-glycoprotein inducers such as St John's wort Values are K_i (nM). The smaller the value, the more strongly the drug binds to the site.

History

Paliperidone (as Invega) was approved by the US

(FDA) for the treatment of

in 2006. Paliperidone was approved by the FDA for the treatment of schizoaffective disorder in 2009. The long-acting injectable form of paliperidone, marketed as Invega Sustenna in the US, and Xeplion in the EU, was approved by the FDA in July 2009. It was initially approved in the European Union in 2007, for schizophrenia, the extended release form and use for schizoaffective disorder were approved in the EU in 2010, and extension to use in adolescents older than 15 years old was approved in 2014.

Society and culture

Deaths

In April 2014, it was reported that 21 Japanese people who had received shots of the long-acting injectable paliperidone palmitate had died, out of 10,700 individuals prescribed the drug.

Brand names

In May 2015, a formulation of paliperidone palmitate was approved by the US

under the brand name Invega Trinza. A similar prolonged release suspension was approved in 2016 by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

originally under the brand name Paliperidone Janssen, later renamed to Trevicta. In September 2021, a newer formulation of paliperidone palmitate, Invega Hafyera, was approved by the US FDA.

References

External links

* {{Authority control Alpha-2 blockers Antipsychotic esters Atypical antipsychotics Belgian inventions Benzisoxazoles Drugs developed by Johnson & Johnson Fluoroarenes Human drug metabolites Lactams Mood stabilizers Palmitate esters Piperidines Prolactin releasers Pyridopyrimidines World Health Organization essential medicines