Chemistry:Paliperidone

Paliperidone, sold under the brand name Invega among others, is an atypical antipsychotic. It is used for the treatment of schizophrenia and schizoaffective disorder. It is marketed by Janssen Pharmaceuticals.

Paliperidone was approved by the US Food and Drug Administration (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. It is on the World Health Organization's List of Essential Medicines. Paliperidone is available as a generic medication.

Medical use

In the United States, paliperidone is indicated 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 schizophrenia and schizoaffective disorder.

Adverse effects

The most common side effects include headache, insomnia, sleepiness, parkinsonism (effects similar to Parkinson's disease such as shaking, muscle stiffness and slow movement), dystonia (involuntary muscle contractions), tremor (shaking), dizziness, akathisia (restlessness), agitation, anxiety, depression, weight gain, nausea, vomiting, constipation, dyspepsia (heartburn), diarrhea, dry mouth, tiredness, toothache, muscle and bone pain, back pain, asthenia (weakness), tachycardia (increased heart rate), high blood pressure, prolonged QT interval (an alteration of the electrical activity of the heart), upper respiratory tract infection (nose and throat infections) and cough.

A 2023 study found that paliperidone may worsen verbal learning and memory compared to placebo 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. 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 and serotonergic antagonism except paliperidone, like its parent compound risperidone, functions as an inverse agonist at 5-HT2A 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 and its metabolite paliperidone are reduced in efficacy by P-glycoprotein inducers such as St John's wort

Pharmacokinetics of long-acting injectable antipsychotics

Medication	Brand name	Class	Vehicle	Dosage	Tmax	t1/2 single	t1/2 multiple	logPc	Ref
Aripiprazole lauroxil	Aristada	Atypical	Watera	441–1064 mg/4–8 weeks	24–35 days	?	54–57 days	7.9–10.0
Aripiprazole monohydrate	Abilify Maintena	Atypical	Watera	300–400 mg/4 weeks	7 days	?	30–47 days	4.9–5.2
Bromperidol decanoate	Impromen Decanoas	Typical	Sesame oil	40–300 mg/4 weeks	3–9 days	?	21–25 days	7.9
Clopentixol decanoate	Sordinol Depot	Typical	Viscoleob	50–600 mg/1–4 weeks	4–7 days	?	19 days	9.0
Flupentixol decanoate	Depixol	Typical	Viscoleob	10–200 mg/2–4 weeks	4–10 days	8 days	17 days	7.2–9.2
Fluphenazine decanoate	Prolixin Decanoate	Typical	Sesame oil	12.5–100 mg/2–5 weeks	1–2 days	1–10 days	14–100 days	7.2–9.0
Fluphenazine enanthate	Prolixin Enanthate	Typical	Sesame oil	12.5–100 mg/1–4 weeks	2–3 days	4 days	?	6.4–7.4
Fluspirilene	Imap, Redeptin	Typical	Watera	2–12 mg/1 week	1–8 days	7 days	?	5.2–5.8
Haloperidol decanoate	Haldol Decanoate	Typical	Sesame oil	20–400 mg/2–4 weeks	3–9 days	18–21 days		7.2–7.9
Olanzapine pamoate	Zyprexa Relprevv	Atypical	Watera	150–405 mg/2–4 weeks	7 days	?	30 days	–
Oxyprothepin decanoate	Meclopin	Typical	?	?	?	?	?	8.5–8.7
Paliperidone palmitate	Invega Sustenna	Atypical	Watera	39–819 mg/4–12 weeks	13–33 days	25–139 days	?	8.1–10.1
Perphenazine decanoate	Trilafon Dekanoat	Typical	Sesame oil	50–200 mg/2–4 weeks	?	?	27 days	8.9
Perphenazine enanthate	Trilafon Enanthate	Typical	Sesame oil	25–200 mg/2 weeks	2–3 days	?	4–7 days	6.4–7.2
Pipotiazine palmitate	Piportil Longum	Typical	Viscoleob	25–400 mg/4 weeks	9–10 days	?	14–21 days	8.5–11.6
Pipotiazine undecylenate	Piportil Medium	Typical	Sesame oil	100–200 mg/2 weeks	?	?	?	8.4
Risperidone	Risperdal Consta	Atypical	Microspheres	12.5–75 mg/2 weeks	21 days	?	3–6 days	–
Zuclopentixol acetate	Clopixol Acuphase	Typical	Viscoleob	50–200 mg/1–3 days	1–2 days	1–2 days		4.7–4.9
Zuclopentixol decanoate	Clopixol Depot	Typical	Viscoleob	50–800 mg/2–4 weeks	4–9 days	?	11–21 days	7.5–9.0
Note: All by intramuscular injection. Footnotes: a = Microcrystalline or nanocrystalline aqueous suspension. b = Low-viscosity vegetable oil (specifically fractionated coconut oil with medium-chain triglycerides). c = Predicted, from PubChem and DrugBank. Sources: Main: See template.

Paliperidone

Site	Ki (nM)
5-HT1A	6.17
5-HT2A	1
5-HT2C	48
5-HT6	24
5-HT7	2.7
α1A	2.5
α2A	3.9
α2C	2.7
D1	41
D2	1.6
D3	3.5
D4	54
D5	29
H1	19
H2	121
mACh	>10,000

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 Food and Drug Administration (FDA) for the treatment of schizophrenia 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.

On December 4, 2014, a 5-year-old Spanish boy, Borja Piriz Matía, died 15 days after he started taking paliperidone (Invega) 3 mg.

In 2019, it was reported that a 33-year-old man died after a single injection of 819 mg of Trevicta (paliperidone palmitate three-monthly injection), with paliperidone poisoning appearing to be the highly likely cause of death.

Suicides

On January 17, 2020, a video titled "Medical Help" was uploaded to YouTube by 26-year-old Wail Ardab of Palatka, Florida, who developed dystonia and insomnia after taking Invega Trinza injections. On March 5, 2020, Ardab committed suicide by jumping from Memorial Bridge in Palatka.

From June 2023 to April 2024, Serbian television presenter and journalist Bojana Nikolić Janković posted to the internet forum Bluelight that she received 4 shots of Invega Sustenna and 2 shots of Invega Trinza due to the stress of her divorce from Ognjen Janković, a member of the hip-hop group Beogradski Sindikat. Janković, known for hosting the show City, wrote that she was bedridden with anhedonia, cognitive issues, low energy and other symptoms after receiving the injections. She died in Belgrade on April 19, 2024, at age 46.

Homicides

On December 28, 2021, 19-year-old Peyton Moyer fatally shot his mother and her boyfriend in Watkinsville, Georgia, while under the influence of the long-acting injectable paliperidone palmitate (Invega Sustenna). On November 2, 2023, Moyer was sentenced to life in prison.

Brand names

In May 2015, a formulation of paliperidone palmitate was approved by the US Food and Drug Administration under the brand name Invega Trinza. A similar prolonged release suspension was approved in 2016 by the European Medicines Agency 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.

External links

• "Paliperidone Injection". https://medlineplus.gov/druginfo/meds/a615032.html.