In short
Paliperidone palmitate is a long-acting injectable antipsychotic medicine used to treat schizophrenia and schizoaffective disorder. It is the active metabolite of risperidone and works by blocking dopamine D2 and serotonin 5-HT2 receptors in the brain. The two registered trials on this page together enrolled 414 participants, including a Phase 3 study in 244 people with first-episode schizophrenia and a Phase 1 bioavailability study in 170 healthy volunteers.
Key points
- Paliperidone palmitate is an atypical antipsychotic given as a long-acting intramuscular injection.
- It is authorised for the treatment of schizophrenia and schizoaffective disorder.
- A Phase 3 trial with 244 participants is studying treatment response in people with a first psychotic episode.
- A completed Phase 1 trial with 170 healthy volunteers compared the bioavailability of a new formulation against the reference product Xeplion.
- The Phase 1 trial measured pharmacokinetic parameters including Cmax and AUC to assess how the body absorbs the drug.
- Known side effects include movement disorders, weight gain, and metabolic changes, with an increased risk of death in elderly people with dementia-related psychosis.
What is paliperidone palmitate?
Paliperidone palmitate is a benzisoxazole derivative and the active metabolite of risperidone. It functions as a dopamine D2 receptor antagonist and a serotonin 5-HT2 receptor antagonist, placing it in the class of atypical antipsychotic agents. The substance is also known under the development code RO92670 and the trade name Invega Sustenna. It is an authorised medicine: the US Food and Drug Administration (FDA) first approved paliperidone in 2006, and the long-acting injectable formulation Invega Sustenna is approved for the treatment of schizophrenia and schizoaffective disorder. In the European trials listed here, the product appears under the trade name Xeplion.
How does paliperidone palmitate work?
Paliperidone palmitate works by blocking two types of receptors in the brain: dopamine D2 receptors and serotonin 5-HT2 receptors. Dopamine and serotonin are chemical messengers involved in mood, perception, and thinking. By reducing the activity of these receptors, the medicine helps to lessen psychotic symptoms such as hallucinations and delusions. Because paliperidone palmitate is formulated as a long-acting injection, the active substance is released slowly into the body over several weeks, which allows for once-monthly dosing after initial loading doses.
Which conditions is it used or studied for?
- Schizophrenia — a long-term mental health condition that can cause hallucinations, delusions, and confused thinking. Paliperidone palmitate is approved for treating schizophrenia in adults and adolescents aged 12 to 17.
- Schizoaffective disorder — a condition combining symptoms of schizophrenia with mood symptoms such as depression or mania. The medicine is approved for this condition as monotherapy or as an add-on to mood stabilisers or antidepressants.
- First psychotic episode of the schizophrenia spectrum — the Phase 3 SchizOMICS trial is studying treatment response in people experiencing their first psychotic episode.
- Treatment-resistant schizophrenia — the same Phase 3 trial also includes people whose schizophrenia has not responded adequately to previous treatment.
How is paliperidone palmitate given?
Paliperidone palmitate is available as an extended-release injectable suspension for intramuscular use. Each injection is administered by a healthcare professional into the deltoid or gluteal muscle. The product information describes an initiation schedule with injections on day 1 and day 8, followed by monthly maintenance doses. An oral extended-release tablet form of paliperidone is also available for daily use. In the Phase 1 trial, the substance was given as a single intramuscular injection at a dose of 25 mg to healthy volunteers.
What do the clinical trials show?
Two registered trials involve paliperidone palmitate. One is an authorised Phase 3 study in schizophrenia, and one is a completed Phase 1 bioavailability study in healthy volunteers.
Which conditions are studied?
The Phase 3 SchizOMICS trial (NCT06060886) is studying schizophrenia, including people with a first psychotic episode and people with treatment-resistant schizophrenia. It is designed to identify biomarkers that predict therapeutic response to aripiprazole or paliperidone after three months of treatment. The Phase 1 trial (2022-502179-48-00) was conducted in healthy subjects to compare the relative bioavailability of a new paliperidone palmitate formulation (LY03010) against Xeplion.
What phases and status do the trials have?
The SchizOMICS study is a Phase 3 trial with the status Authorised, meaning it has received approval to proceed. The bioavailability study is a Phase 1 trial with the status Completed. The Phase 3 trial enrolled 244 participants, while the Phase 1 trial enrolled 170 healthy volunteers.
What are the trials measuring?
The Phase 3 trial measures therapeutic response using the PANSS (Positive and Negative Syndrome Scale) and CGI-S (Clinical Global Impression – Severity) scales, as well as the proportion of participants who discontinue their first antipsychotic within three months and the time to discontinuation during the first year. The Phase 1 trial measured pharmacokinetic parameters: Cmax (maximum drug concentration in the blood), AUC0-t and AUC0-∞ (how much of the drug stays in the blood over time), and tmax (time to reach maximum concentration).
What side effects are known?
The prescribing information carries a boxed warning that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death, and paliperidone is not approved for use in this population. As an atypical antipsychotic that blocks dopamine D2 receptors, paliperidone can cause movement-related side effects and other effects typical of this drug class. The label also notes that dosing adjustments may be needed based on tolerability, which reflects that side effects can occur and may require dose changes.