Does Paxlovid Affect the Nervous System? A Comprehensive Look at Neurological Side Effects

October 10, 2025 •

4 min read

Based on analysis of FDA adverse event data, Paxlovid has been associated with a higher number of neurologic-related adverse events compared to other COVID-19 medications used to treat the virus. So, does Paxlovid affect the nervous system? The answer is yes, though primarily with mild and often transient symptoms, with the potential for more significant effects due to drug interactions.

Quick Summary

A data-driven analysis shows Paxlovid is linked to various nervous system adverse events, including altered taste, headaches, and sensory issues. Drug interactions, influenced by ritonavir, can also impact central nervous system function, requiring careful consideration.

Key Points

Altered Taste (Dysgeusia): This is the most frequently reported neurological side effect of Paxlovid, often described as a metallic or bitter taste.
Drug-Drug Interactions: The ritonavir in Paxlovid is a strong CYP3A4 inhibitor, which can dangerously increase the levels of other medications that affect the nervous system.
Headaches and Other Sensory Disturbances: Headaches, dizziness, and a diminished sense of smell (anosmia) are also reported nervous system effects.
Impact on Cognitive Function: Less commonly, patients have reported issues such as brain fog, memory impairment, and disturbances in attention.
Overlap with COVID-19 Symptoms: Some nervous system symptoms are also common with COVID-19, complicating the determination of whether the drug or the virus is the cause.
Potential Long-Term Benefits: One study found that taking Paxlovid may be associated with a reduced long-term risk of neurocognitive and psychiatric issues following COVID-19.

The Components of Paxlovid: Nirmatrelvir and Ritonavir

Paxlovid is a combination of two antiviral drugs: nirmatrelvir and ritonavir. Nirmatrelvir is the active component that inhibits the SARS-CoV-2 main protease, an enzyme critical for the virus's replication. Ritonavir's role is not to act against the virus directly, but to boost the levels of nirmatrelvir in the body. It achieves this by acting as a powerful inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme system in the liver, which is responsible for metabolizing many drugs, including nirmatrelvir. This process allows for lower, less frequent dosing of nirmatrelvir while maintaining therapeutic levels, but it also creates a high potential for drug-drug interactions that can affect the nervous system.

Reported Neurological Adverse Events

While Paxlovid is generally considered safe and effective, real-world data and post-marketing surveillance have identified a range of neurological adverse reactions. A 2025 study analyzing adverse event data from the FDA database found that Paxlovid had the highest number and strongest signal for neurologic-related adverse events compared to other COVID-19 drugs. The most common reports involve sensory disturbances, but other symptoms have also been documented.

Common Sensory and General Symptoms

Dysgeusia and Ageusia: A significant number of patients report an altered or completely lost sense of taste. Dysgeusia, often described as a metallic or bitter taste, was the most frequently reported neurological adverse event in the FDA data analysis. These sensory changes are typically temporary and resolve after the five-day treatment course.
Headache: Headaches are a relatively common side effect, reported by a notable number of users. While some may experience migraines, many report a less severe headache.
Anosmia: A loss of smell, anosmia, has also been reported in some patients taking Paxlovid. While loss of smell is a well-known symptom of COVID-19 itself, studies indicate it can also be linked to the medication.
Dizziness and Somnolence: Some patients have reported feeling dizzy or experiencing somnolence (drowsiness) during their treatment.

Less Common but Reported Symptoms

Brain Fog and Cognitive Issues: Post-marketing reports have indicated cases of brain fog, mental impairment, and memory impairment in some individuals taking Paxlovid.
Balance and Movement Disorders: Though less frequent, balance disorders and other movement-related issues have been reported in adverse event databases.
Neuropsychiatric Effects: Studies have observed psychiatric side effects like anxiety, sleep disturbances, and delirium, especially in comparison to other antivirals.

The Critical Factor of Drug-Drug Interactions

One of the most important considerations regarding Paxlovid's effect on the nervous system is its potential for significant drug-drug interactions (DDIs). The ritonavir component inhibits CYP3A4, which is responsible for metabolizing numerous other medications, including those used for neurological and psychiatric conditions. This can lead to increased plasma concentrations of co-administered drugs, potentially causing toxicity and serious adverse events.

Interactions with CNS-Active Medications

Anxiolytics: Benzodiazepines such as midazolam or long-acting ones like diazepam are metabolized by CYP3A4. Co-administration with Paxlovid is contraindicated, as it can lead to excessive sedation and respiratory depression.
Anticonvulsants: Certain anticonvulsant medications (e.g., carbamazepine, phenytoin) are strong CYP3A4 inducers. Taking Paxlovid with these can significantly reduce the concentration of nirmatrelvir, compromising its effectiveness.
Serotonin Syndrome: In some instances, Paxlovid initiation with other serotonergic agents has precipitated serotonin syndrome, a potentially life-threatening condition involving increased serotonin levels in the central and peripheral nervous systems.

Differentiating Drug Effects from COVID-19's Impact

It is crucial to recognize that SARS-CoV-2 infection itself is known to cause a wide range of neurological and neuropsychiatric issues. The virus is neurotropic, meaning it can affect the nervous system directly, and the inflammatory response to the infection can also cause indirect neurological damage. This can make it difficult for researchers and clinicians to definitively separate drug-induced adverse events from symptoms of the underlying disease. However, careful analysis of adverse event reporting, such as the data mining study mentioned earlier, helps distinguish potential drug effects. Interestingly, one study suggested that Paxlovid use might actually be associated with a reduced long-term risk of neurocognitive and psychiatric complications in some patients.

Comparison of Antiviral Therapies and Nervous System Effects

To put Paxlovid's nervous system effects into context, it is helpful to compare it with other antiviral treatments for COVID-19, such as remdesivir and molnupiravir. A comparative analysis of neuropsychiatric adverse reactions reported to pharmacovigilance databases helps highlight differences.


Feature	Paxlovid (Nirmatrelvir/Ritonavir)	Remdesivir	Molnupiravir
Mechanism	Inhibits viral protease; ritonavir boosts nirmatrelvir via CYP3A4 inhibition.	Inhibits viral RNA polymerase, blocking viral replication.	Induces viral RNA mutations to inhibit replication.
Neurological ADRs	Highest number and strongest signal among COVID-19 antivirals. Common: altered taste, headache. Less common: brain fog, cognitive issues, sleep disturbances.	Lower reported frequency of neurological side effects compared to Paxlovid.	No clinically significant interactions identified. No notable neurological side effects reported.
Risk of Drug Interactions	High, especially with CYP3A4 substrates, potentially causing serious CNS effects.	Minimal risk, though it is a CYP3A4 substrate.	Minimal, no major interactions.
Benefit for Long-Term Sequelae	Some evidence suggests a potential reduction in long-term neuropsychiatric sequelae.	Data are less clear regarding long-term neuropsychiatric effects.	No specific data identified regarding long-term neuropsychiatric effects.

Conclusion

Based on available post-marketing surveillance and real-world data, Paxlovid does affect the nervous system, but the impact is varied. Most patients experience mild and temporary neurological side effects, primarily sensory disturbances like altered taste and headaches. The risk of more serious effects often stems from the ritonavir component's potent CYP3A4 inhibition, which can lead to dangerous drug-drug interactions with other CNS-active medications. Therefore, healthcare providers must perform a thorough medication review before prescribing Paxlovid to mitigate these risks. For patients concerned about these effects, a discussion with a healthcare provider is essential to weigh the risks of potential side effects against the proven benefits of Paxlovid in preventing severe COVID-19 outcomes.

Resources

The U.S. Food and Drug Administration (FDA) provides a comprehensive list of potential side effects and drug interactions related to Paxlovid. PAXLOVID Side Effects on FDA Website

Frequently Asked Questions

Yes, an altered sense of taste, known as dysgeusia, is the most common neurological side effect associated with taking Paxlovid, often presenting as a metallic or bitter taste.

It can be difficult to tell, as many symptoms like altered taste, smell, and headaches are caused by both the virus and the medication. If your symptoms are significantly different from or worsen with the start of Paxlovid, you should consult your healthcare provider.

Most of the reported neurological side effects, such as taste disturbances and headaches, are temporary and typically resolve after the five-day treatment course is complete. Significant, long-lasting effects are rare.

Some reports have linked Paxlovid to cognitive symptoms like 'brain fog,' mental impairment, and attention disturbances, though these are less common than sensory changes. A healthcare provider can help assess these symptoms.

You must discuss all your current medications with your doctor before starting Paxlovid. The ritonavir in Paxlovid can have serious interactions with many drugs, including certain anxiolytics and anticonvulsants, potentially causing severe side effects.

Some real-world data analysis suggests that female patients might be more likely to experience certain neurologic adverse reactions, such as dysgeusia, headache, and anosmia, within the first 30 days of treatment.

While the short-term neurological effects are well-documented, one study suggested that Paxlovid may actually reduce the long-term risk of neuropsychiatric issues associated with COVID-19. Consult your doctor if you have lingering concerns.