What is Paliperidone and How Does It Work?
Paliperidone, known by brand names like Invega, is a second-generation (atypical) antipsychotic medication [1.2.5]. It is the primary active metabolite of risperidone [1.7.1]. Its primary use is in the treatment of schizophrenia in adults and adolescents, and it is also approved for schizoaffective disorder [1.6.1, 1.6.3]. The medication works by altering the activity of neurotransmitters in the brain, specifically by acting as an antagonist for dopamine type 2 (D2) and serotonin type 2A (5-HT2A) receptors [1.7.1, 1.7.3, 1.7.6]. By blocking these receptors, paliperidone helps to improve thinking, mood, and behavior, reducing symptoms like hallucinations, delusions, and disorganized thought [1.2.5, 1.6.6]. It is available in oral extended-release tablets and as a long-acting intramuscular injection [1.6.1, 1.6.2].
Common Side Effects
Many individuals taking paliperidone may experience a range of common side effects. These are often dose-related and may decrease as the body adjusts to the medication. It's important to report any persistent or bothersome side effects to a healthcare provider.
- Movement-related (Extrapyramidal Symptoms): These are among the most frequent side effects and include restlessness (akathisia), the need to keep moving, muscle stiffness, shuffling walk, tremors, and slowed movements [1.2.1, 1.2.3].
- General Effects: Drowsiness or sleepiness, headache, and dizziness are commonly reported [1.2.3, 1.3.5]. Dizziness upon standing (orthostatic hypotension) can also occur [1.2.2, 1.4.4].
- Metabolic and Weight Changes: Weight gain is a notable side effect [1.2.2, 1.3.4].
- Gastrointestinal Issues: Common GI effects include dry mouth, constipation, nausea, vomiting, and upper abdominal pain [1.2.1, 1.3.4].
- Other common effects: Anxiety, trouble sleeping, and upper respiratory tract infections like a stuffy or runny nose can also occur [1.2.1, 1.3.5]. For those receiving injections, pain, swelling, or redness at the injection site is common [1.2.2, 1.2.6].
Serious and Long-Term Side Effects
Paliperidone carries a risk of more severe, and in some cases, irreversible side effects. These require immediate medical attention.
- Tardive Dyskinesia (TD): A significant long-term risk associated with all antipsychotics is TD, a condition characterized by involuntary, repetitive body movements [1.2.7]. This can include grimacing, lip-smacking, and rapid movements of the tongue, face, arms, or legs. The risk increases with prolonged use and may be permanent [1.3.5, 1.2.2].
- Neuroleptic Malignant Syndrome (NMS): NMS is a rare but life-threatening reaction to antipsychotic drugs [1.2.3]. Symptoms include high fever, severe muscle stiffness, confusion, altered mental status, sweating, and irregular heartbeat or blood pressure [1.2.6, 1.3.5]. NMS requires immediate hospitalization [1.2.3].
- Metabolic Changes: Beyond simple weight gain, paliperidone can cause significant metabolic issues, including high blood sugar (hyperglycemia) which can lead to diabetes, and increased cholesterol and triglyceride levels (dyslipidemia) [1.2.3, 1.2.7]. Regular monitoring of weight, blood glucose, and lipid panels is essential [1.4.4].
- Hyperprolactinemia: The medication often elevates levels of the hormone prolactin [1.2.3]. This can lead to missed menstrual periods, breast milk production (in both sexes), breast enlargement in males (gynecomastia), and decreased sexual ability or desire [1.2.2, 1.3.5].
- Cardiovascular Effects: Paliperidone can cause changes in heart rhythm (QT prolongation), a fast heartbeat (tachycardia), and a drop in blood pressure when standing up (orthostatic hypotension), which increases the risk of falls [1.2.7, 1.8.6]. There is also an increased risk of stroke in elderly patients with dementia-related psychosis, for which this drug is not approved [1.2.3].
- Other Serious Risks: Other potential serious effects include seizures, difficulty swallowing (dysphagia), low white blood cell counts (leukopenia, neutropenia), and a painful, prolonged erection (priapism) that requires emergency treatment [1.2.2, 1.2.7].
Comparison with Risperidone
Paliperidone is the active metabolite of risperidone, meaning they are closely related and share a similar mechanism of action [1.7.1]. However, there are some differences in their side effect profiles and how they are processed by the body.
| Feature | Paliperidone | Risperidone |
|---|---|---|
| Primary Form | Active metabolite, less hepatic metabolism [1.7.6] | Parent drug, extensive metabolism [1.5.1] |
| Orthostatic Hypotension | Suggested to cause less orthostatic hypotension [1.5.3] | More potent blocker of alpha-2 receptors, may have higher risk [1.5.3] |
| Cognitive Effects | Some studies suggest a switch from risperidone may improve cognitive abilities [1.5.2] | May have a slightly higher risk of neurotoxicity compared to paliperidone [1.5.2] |
| Weight Gain & Metabolism | Both cause weight gain and metabolic changes; effects may be slightly less than risperidone [1.5.4, 1.5.5] | Also carries a significant risk of weight gain and metabolic changes [1.5.4, 1.5.5] |
| Hyperprolactinemia | Has a prolactin-elevating effect similar to or greater than risperidone [1.8.6, 1.6.4] | Known for causing significant elevation in prolactin levels [1.3.5] |
Managing Side Effects and Important Considerations
Managing the side effects of paliperidone involves close collaboration with a healthcare provider.
- Regular Monitoring: Patients should have regular appointments to check weight, blood sugar, and cholesterol levels [1.4.4]. An Abnormal Involuntary Movement Scale (AIMS) test should be done regularly to monitor for tardive dyskinesia [1.2.5].
- Lifestyle Adjustments: To manage orthostatic hypotension, patients should stand up slowly from sitting or lying positions [1.4.2]. To avoid overheating, it's important to drink plenty of water and avoid vigorous exercise in hot weather, as the drug can impair the body's ability to regulate temperature [1.4.1, 1.4.3].
- Drug Interactions: Paliperidone can interact with many other drugs. It should not be taken with alcohol or other CNS depressants, as this can increase drowsiness [1.2.1]. It can also interact with blood pressure medications, levodopa (used for Parkinson's disease), and drugs that prolong the QT interval [1.8.1]. Patients must inform their doctor of all medications, including over-the-counter drugs and supplements, they are taking [1.2.2].
- Contraindications: Paliperidone is contraindicated in individuals with a known hypersensitivity to paliperidone or risperidone [1.8.6]. It should be used with caution in patients with a history of seizures, heart problems, kidney disease, or low white blood cell counts [1.2.6]. It is not approved for treating dementia-related psychosis in elderly patients due to an increased risk of death [1.2.3].
Conclusion
Paliperidone is an effective medication for managing the symptoms of schizophrenia and schizoaffective disorder. However, it is associated with a wide range of potential side effects, from common issues like drowsiness and movement problems to severe, long-term risks such as tardive dyskinesia and significant metabolic changes. Patients and their caregivers must be aware of these risks, maintain open communication with their healthcare provider, and adhere to recommended monitoring to ensure the benefits of treatment outweigh the potential harms. Never stop taking the medication abruptly without consulting a doctor, as this can lead to withdrawal or worsening of symptoms.
For more detailed information, consult a medical professional or visit an authoritative source such as The National Alliance on Mental Illness (NAMI).
