General Information

Invega and its various formulations is an active metabolite of risperidone. It is an antagonist and thus interferes with neurotransmitter communication in the brain. It blocks dopamine type 2, serotonin type 2, and alpha 2 adrenergic receptors, all of which have been implicated in schizophrenia.

Invega is specifically indicated for the treatment of schizophrenia as monotherapy and as an adjunct to mood stabilizers and/or antidepressants

Invegga Sustenna (1-month injection) is specifically indicated for the treatment of schizophrenia in adults as monotherapy and as an adjunct to mood stabilizers or antidepressants

Invegga Trinza (3-month injection) is specifically indicated for the treatment of schizophrenia in patients after they have been adequately treated with Invegga Sustenna for at least four months.

Invega Hayfera (every-six-month injection) is indicated for the treatment of schizophrenia in adults after they have been adequately treated with:

• A once-a-month paliperidone palmitate extended-release injectable suspension (e.g., Invega Sustenna) for at least four months or
• An every-three-month paliperidone palmitate extended-release injectable suspension (e.g., Invega Trinza) for at least one three-month cycle

Invega is supplied as the following formulations: 

• Invega (paliperidone extended-release (ER) tablets),
• Invega Sustenna (1-month paliperidone palmitate extended-release injectable suspension)
• Invega Trinza (3-month paliperidone palmitate)
• Invega Hayfera (6-month paliperidone palmitate)

Mechanism of Action

Paliperidone is the major active metabolite of risperidone. The mechanism of action of paliperidone is unclear. However, the drug’s therapeutic effect in schizophrenia could be mediated through a combination of central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptor antagonism.

Side Effects

Adverse events associated with the use of Invega may include, but are not limited to, the following:

• Parkinsonism
• Akathisia
• Dyskinesia
• Tachycardia
• Headache
• Somnolence
• Anxiety
• Hyperkinesia
• Extrapyramidal disorder
• Dystonia

The Invega drug labels all come with the following Black Box Warning: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. None of the Invega formulations are approved for use in patients with dementia-related psychosis.

Clinical Trial Results

FDA approval of Invega was based on the results of three clinical trials. These placebo-controlled, active-controlled (olanzapine), fixed-dose trials enrolled 1,665 non-elderly adult subjects who met DSM-IV criteria for schizophrenia, internationally. Subjects received placebo or Invega at 3, 6, 9, 12, and 15 mg/day for six weeks. Efficacy was evaluated using the Positive and Negative Syndrome Scale (PANSS) and the Personal and Social Performance (PSP) scale. Results revealed all doses of Invega to be superior to placebo on both the PANSS and PSP scales. The mean effects at all doses were fairly similar, although the higher doses in all studies were numerically superior.

The FDA approval of Invega Hayfera was based on the results of a 12-month, randomized, double-blind, non-inferiority Phase 3 global study that enrolled 702 adults (ages 18-70) living with schizophrenia from 20 countries. The results showed non-inferiority of INVEGA HAFYERA™ compared to Invega Trinza on the primary endpoint of time to first relapse at the end of the 12-month period. Results found that 92.5 percent of patients treated with Invega Hayfera and 95 percent treated with Invega Trinza were relapse-free at 12 months. Relapse was defined as psychiatric hospitalization, increase in Positive and Negative Syndrome Scale [PANSS] total score, increase in individual PANSS item scores, self-injury, violent behavior, or suicidal/homicidal ideation.