Does Paliperidone Cause Diarrhea? An In-Depth Pharmacological Review

October 9, 2025 •

4 min read

In clinical trials for Invega Sustenna, approximately 3% of patients experienced diarrhea, compared to 2% on a placebo [1.2.3]. This article examines the question: Does paliperidone cause diarrhea, its mechanisms, and how to manage this side effect?

Quick Summary

Paliperidone can cause diarrhea, although it is considered a less common side effect [1.2.1]. This text explores the frequency of this gastrointestinal issue, effective management strategies, and other potential side effects of the medication.

Key Points

Diarrhea is a Side Effect: Paliperidone can cause diarrhea, though it's generally considered a less common side effect, affecting a small percentage of users in clinical trials [1.2.1, 1.2.3].
Mechanism of Action: Paliperidone, the active metabolite of risperidone, works by blocking dopamine D2 and serotonin 5-HT2A receptors in the brain [1.5.3].
Other GI Effects: Besides diarrhea, other common gastrointestinal side effects include nausea, vomiting, constipation, and abdominal pain [1.6.1].
Management is Key: Managing paliperidone-induced diarrhea involves staying hydrated, adjusting your diet to bland foods, and consulting a doctor before using OTC anti-diarrhea medications [1.4.2, 1.4.4].
Do Not Stop Medication: Patients should never stop taking paliperidone without consulting their healthcare provider, as this can worsen psychiatric symptoms [1.4.7].
When to See a Doctor: Seek medical attention for severe, bloody, or persistent diarrhea, or if it's accompanied by signs of dehydration or fever [1.4.5, 1.2.5].
Comparison with Risperidone: Paliperidone and its parent drug, risperidone, have very similar gastrointestinal side effect profiles [1.7.1, 1.2.8].

Understanding Paliperidone and Its Role

Paliperidone is a second-generation (atypical) antipsychotic medication used primarily to treat schizophrenia and schizoaffective disorder in adults and adolescents [1.3.4, 1.3.8]. Marketed under brand names like Invega, Invega Sustenna, Invega Trinza, and Invega Hafyera, it works by rebalancing dopamine and serotonin levels in the brain [1.3.8]. Its mechanism of action involves antagonizing, or blocking, dopamine D2 and serotonin 5-HT2A receptors [1.5.3, 1.5.6]. This modulation helps to alleviate symptoms such as hallucinations, delusions, and disorganized thinking [1.3.8]. Paliperidone is actually the primary active metabolite of risperidone, another common antipsychotic, meaning they share a similar mechanism of action [1.5.1, 1.5.4]. It is available in various formulations, including extended-release oral tablets and long-acting injections administered monthly, every three months, or twice a year [1.5.1, 1.5.7].

Does Paliperidone Cause Diarrhea?

Yes, paliperidone can cause diarrhea, though it is listed as a less common or common side effect, depending on the formulation [1.2.1, 1.6.1]. In clinical trials for Invega Sustenna (the 1-month injection), diarrhea was reported in about 3% of patients, a rate only slightly higher than the 2% observed in the placebo group [1.2.3]. For the extended-release tablets, diarrhea is considered a common side effect, occurring in 1% to 10% of users [1.6.1]. While not as prevalent as side effects like drowsiness, dizziness, or extrapyramidal symptoms (movement-related issues), gastrointestinal disturbances including diarrhea, nausea, vomiting, and abdominal pain are well-documented [1.2.2, 1.6.4]. The exact mechanism by which paliperidone induces diarrhea isn't fully understood but is believed to be related to its effects on various receptors in the gastrointestinal tract.

Other Common Side Effects of Paliperidone

Patients taking paliperidone may experience a range of side effects beyond gastrointestinal issues. It's important for patients to be aware of these potential effects and communicate with their healthcare provider.

Most Common Side Effects:

Movement-related (Extrapyramidal Symptoms): This can include akathisia (restlessness or a constant urge to move), tremors (shaking), muscle stiffness, and shuffling movements [1.3.2, 1.3.7].
Metabolic Changes: Paliperidone can cause significant weight gain, high blood sugar (hyperglycemia), and changes in cholesterol levels [1.3.6]. Regular monitoring of weight and blood work is often recommended [1.3.6].
Cardiovascular Effects: Tachycardia (fast heart rate) and orthostatic hypotension (a drop in blood pressure upon standing) are common [1.6.4].
Central Nervous System (CNS) Effects: Sleepiness, drowsiness, headache, and dizziness are frequently reported [1.3.7, 1.6.4].
Hormonal Changes: The medication can increase levels of the hormone prolactin (hyperprolactinemia), leading to missed menstrual periods, breast discharge, or breast enlargement in males [1.3.2, 1.3.6].

Comparison of GI Side Effects: Paliperidone vs. Risperidone

Paliperidone is the active metabolite of risperidone, meaning they are closely related [1.5.1]. Both medications share a similar side effect profile, including gastrointestinal issues. The table below compares their common GI side effects.


Side Effect	Paliperidone (Invega)	Risperidone (Risperdal)
Nausea	Common [1.6.1]	Common [1.2.8]
Vomiting	Common [1.6.1]	Common [1.2.8]
Diarrhea	Common [1.6.1]	Common [1.2.8]
Constipation	Common [1.6.1]	Common [1.2.8]
Abdominal Pain	Common [1.6.1]	Common [1.2.8]
Dyspepsia (Indigestion)	Common [1.6.1]	Common [1.2.8]
Dry Mouth	Common [1.6.1]	Common [1.2.8]

While the profiles are similar, some studies suggest that certain side effects like restlessness and nausea might be more common with risperidone, whereas tachycardia may be more frequent with paliperidone [1.7.2]. However, differences in metabolic side effects between the two are generally considered modest [1.7.5].

Managing Paliperidone-Induced Diarrhea

If you experience diarrhea while taking paliperidone, it is crucial not to stop the medication without consulting your doctor [1.4.7]. Sudden discontinuation can lead to a worsening of psychiatric symptoms. There are several strategies to manage this side effect:

Stay Hydrated: The most important step is to replace lost fluids and electrolytes. Drink plenty of water, broths, or oral rehydration solutions [1.4.2].
Dietary Adjustments: Adopt a bland diet, often referred to as the BRAT diet (bananas, rice, applesauce, toast) [1.6.2]. Avoid high-fiber, spicy, greasy, or fried foods [1.4.4]. Limiting caffeine and alcohol can also help [1.4.4].
Over-the-Counter (OTC) Medications: Talk to your healthcare provider about using an antidiarrheal medication like loperamide (Imodium) [1.4.4]. It is important to rule out an infectious cause of diarrhea before starting these medications [1.4.2].
Skin Care: Frequent bowel movements can irritate the skin around the anus. Keep the area clean and dry. Using a barrier cream can provide protection [1.4.4].
Dose Adjustment: In some cases, a healthcare provider might adjust the dose of paliperidone to see if the side effect subsides [1.3.5].

When to Consult a Doctor

While mild diarrhea may resolve on its own, you should contact your doctor if you experience:

Severe, persistent, or bloody diarrhea [1.4.5].
Signs of dehydration, such as extreme thirst, decreased urination, dizziness, or weakness [1.2.5, 1.3.3].
Diarrhea accompanied by a high fever, severe abdominal pain, or vomiting [1.4.8].
Any other concerning or severe side effects from the medication.

Conclusion

Paliperidone can indeed cause diarrhea, but it is typically a manageable and less frequent side effect compared to others like drowsiness or movement-related issues [1.2.1, 1.6.1]. The incidence is relatively low, and for many patients, the therapeutic benefits of paliperidone for managing schizophrenia or schizoaffective disorder outweigh this discomfort. Open communication with a healthcare provider is essential for managing diarrhea through hydration, diet, and potentially medication, without compromising psychiatric treatment. Patients should never alter their medication regimen without professional medical advice [1.4.7].

For more information on mental health medications, you can visit the National Alliance on Mental Illness (NAMI).

Frequently Asked Questions

Diarrhea is listed as a common (1-10%) to less common side effect of paliperidone. In some clinical studies for the injectable form, it occurred in about 3% of patients [1.6.1, 1.2.3].

You should speak with your healthcare provider before taking over-the-counter medications like loperamide (Imodium). They will need to ensure your diarrhea is not from an infection before recommending it [1.4.2, 1.4.4].

It is recommended to eat bland foods, such as those in the BRAT diet (bananas, rice, applesauce, and toast). Avoid spicy, greasy, and high-fiber foods until the diarrhea resolves [1.6.2, 1.4.4].

In some cases, mild, drug-induced diarrhea may resolve as your body adjusts to the medication. However, if it persists or is severe, you should consult your doctor [1.4.1].

The most common side effects include movement-related issues (like restlessness and tremors), drowsiness, dizziness, weight gain, and increased heart rate [1.3.2, 1.3.7].

Paliperidone is the major active metabolite of risperidone. This means they are chemically very similar and work in the same way, and thus have very similar side effect profiles [1.5.1].

You should call your doctor if your diarrhea is severe, contains blood, lasts for more than a couple of days, or if you have signs of dehydration like dizziness, dry mouth, and decreased urination [1.2.5, 1.4.5].