Can Pregabalin Cause Altered Mental Status?

October 7, 2025 •

5 min read

According to the FDA label, a significant percentage of patients in clinical trials reported confusion and thinking abnormalities while taking pregabalin. Therefore, understanding how pregabalin can cause altered mental status is crucial for patients and healthcare providers to manage risks and ensure safe treatment.

Quick Summary

Pregabalin can cause cognitive and psychiatric side effects, including confusion, impaired concentration, and disorientation. Risk factors like high doses and renal impairment can increase the likelihood of these adverse effects.

Key Points

Alterations are a Known Side Effect: Pregabalin can directly affect the central nervous system, leading to altered mental status, which is a recognized adverse effect documented in its FDA labeling.
Symptoms Range in Severity: The spectrum of cognitive changes can range from common issues like dizziness and difficulty concentrating to more severe, though rare, conditions such as delirium and psychosis.
Dosage is a Key Factor: The incidence and severity of cognitive and psychiatric side effects are often dose-dependent, increasing with higher daily dosages of the medication.
Risk Increases with Co-use: Combining pregabalin with other CNS depressants, including alcohol and opioids, dramatically increases the risk of serious side effects like confusion, respiratory depression, and extreme sedation.
Abrupt Discontinuation is Dangerous: Stopping pregabalin abruptly can trigger withdrawal symptoms, including confusion, anxiety, and seizures. Any dose reduction must be tapered gradually under medical supervision.
Vulnerable Groups Face Higher Risk: Older adults, patients with renal impairment, and individuals with a history of substance abuse are more susceptible to pregabalin's cognitive and psychiatric side effects.

Understanding Pregabalin's Central Nervous System Effects

Pregabalin, commonly known by the brand name Lyrica, is a medication approved to treat conditions such as neuropathic pain, fibromyalgia, and certain seizure disorders. As a gabapentinoid, it functions by binding to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system (CNS). This action reduces the release of several excitatory neurotransmitters, calming overactive nerve signals. While this mechanism is effective for its intended uses, it also directly influences brain activity, which can result in various CNS side effects, including altered mental status.

Common adverse reactions affecting the CNS, reported frequently in clinical trials, include dizziness, somnolence, and impaired concentration. These effects are often dose-dependent, meaning they are more likely to occur and be more severe at higher doses. In some patients, these cognitive disturbances can escalate to more significant issues, constituting an altered mental status that requires medical attention.

The Mechanisms Behind Pregabalin-Induced Mental Changes

The altered mental status caused by pregabalin is a direct result of its pharmacological actions within the brain. By reducing the release of neurotransmitters such as glutamate, noradrenaline, and substance P, pregabalin can disrupt the normal balance of neural communication. This disruption can lead to a spectrum of cognitive and psychiatric symptoms. The FDA label and postmarketing reports explicitly list several such effects.

Some of the specific ways pregabalin can alter mental status include:

Confusion: Patients may experience disorientation or a state of mental unclarity, which is a reported side effect occurring in 2-7% of patients in clinical trials.
Cognitive Dysfunction: This can present as difficulty with concentration, attention, and memory impairment. Some studies have confirmed a negative impact on cognitive function, affecting performance on tests of attention and processing speed, especially at higher doses.
Delirium and Psychosis: Although rare, cases of delirium (an acute state of severe confusion and disorientation), visual hallucinations, and other psychotic symptoms have been reported. These can occur even with appropriate therapeutic doses, especially in vulnerable individuals.
Withdrawal Symptoms: Abrupt or rapid discontinuation of pregabalin can also trigger altered mental status, including confusion, disorientation, anxiety, and even psychotic symptoms.

Risk Factors for Developing Cognitive Side Effects

Several factors can increase an individual's susceptibility to experiencing altered mental status while on pregabalin:

Higher Dosage: The risk and severity of cognitive side effects, such as confusion and dizziness, are strongly linked to the dose of pregabalin. Higher doses have a greater impact on CNS activity.
Older Age: Elderly patients are particularly vulnerable to pregabalin's cognitive effects. Age-related changes in metabolism and kidney function can increase the drug's concentration in the body, magnifying side effects.
Renal Impairment: Since pregabalin is primarily eliminated by the kidneys, patients with kidney problems are at a higher risk of drug accumulation and subsequent side effects. Dose adjustments are typically necessary for this population.
Concurrent Use of CNS Depressants: Combining pregabalin with other CNS depressants, such as alcohol, opioids, or benzodiazepines, significantly increases the risk of severe side effects, including profound sedation, respiratory depression, and confusion.
History of Substance Abuse: Individuals with a history of substance use disorder, particularly involving other CNS depressants like opioids, have a higher risk of misuse and subsequent adverse psychiatric effects with pregabalin.

Managing and Addressing Altered Mental Status

If a patient experiences symptoms of altered mental status, it is critical to seek medical advice. Management strategies focus on symptom resolution while maintaining patient safety. The primary approaches include:

Dosage Adjustment: The most common and effective strategy is to lower the dose of pregabalin. Since cognitive side effects are often dose-dependent, a reduction can help mitigate symptoms.
Discontinuation (Tapering): If symptoms are severe or persistent, discontinuing the medication may be necessary. Abrupt discontinuation is strongly discouraged, as it can cause significant withdrawal symptoms, including seizures and psychosis. A gradual taper over at least one week, as recommended by the FDA, is the safest method.
Patient Monitoring: Continuous monitoring is essential, especially during the first few weeks of treatment or after a dose change. For patients with a history of depression or mood disorders, this monitoring should also include observing for new or worsening psychiatric symptoms, including suicidal thoughts.
Addressing Risk Factors: Healthcare providers should consider a patient's overall health profile, including kidney function, age, and other medications, to minimize risk. For instance, adjusting the dose for patients with renal impairment is a crucial preventative step.

Comparison: Pregabalin vs. Gabapentin Cognitive Effects


Feature	Pregabalin (Lyrica)	Gabapentin (Neurontin)
Mechanism	Binds to α2δ subunit of voltage-gated calcium channels to reduce neurotransmitter release.	Also binds to α2δ subunit, though there are some differences in binding affinity and activity.
Cognitive Impairment	Explicitly lists cognitive side effects like confusion, amnesia, and concentration problems on FDA label.	Also known to cause cognitive difficulties, such as confusion and memory impairment.
Dizziness/Somnolence	Very common side effects, often more frequent than with gabapentin in some comparative studies.	Also common, though may have a slightly different incidence profile depending on the formulation and patient group.
Polypharmacy Risk	Combining with other CNS depressants (opioids, alcohol) significantly increases risk of sedation and respiratory depression.	Also carries a significant risk when combined with other CNS depressants.
Withdrawal Symptoms	Abrupt discontinuation can cause withdrawal symptoms including confusion, anxiety, insomnia, and seizures.	Abrupt discontinuation can cause similar withdrawal symptoms, including anxiety, insomnia, and seizures.

Conclusion

In summary, it is well-established that pregabalin can cause altered mental status, encompassing a range of symptoms from mild concentration difficulties to rare but serious occurrences like delirium and psychosis. The risk of these effects is heightened by factors such as higher dosages, advanced age, impaired kidney function, and the concomitant use of other CNS-depressing substances like alcohol or opioids. While many patients tolerate the medication well, especially with careful dose titration, awareness and proactive monitoring are crucial. For managing such side effects, dosage reduction or a gradual taper under medical supervision is the recommended approach to ensure symptom resolution and prevent withdrawal complications. Patients should maintain open communication with their healthcare providers to balance therapeutic benefits with the potential for adverse cognitive effects. For more information on pregabalin, consult the official MedlinePlus drug information page at the National Library of Medicine.

Frequently Asked Questions

Pregabalin can cause various forms of altered mental status, including confusion, difficulty concentrating, impaired memory, disorientation, and dizziness. In rare cases, it can also lead to more serious issues like delirium and visual hallucinations.

These side effects are linked to pregabalin's mechanism of action. By binding to calcium channels in the central nervous system, it reduces the release of excitatory neurotransmitters, which can disrupt normal brain function and result in cognitive impairment.

Yes, older adults are considered a particularly vulnerable population. They are more likely to experience cognitive side effects such as confusion, and age-related changes in kidney function can lead to higher concentrations of the drug in their system.

Yes, it can. Both pregabalin and alcohol are central nervous system depressants, and taking them together can lead to enhanced sedative effects, extreme drowsiness, increased confusion, and a heightened risk of respiratory depression.

If you experience confusion or any other symptoms of altered mental status, you should not stop taking the medication suddenly. Instead, contact your healthcare provider immediately to discuss your symptoms. They may recommend a dosage adjustment or a gradual tapering plan.

The cognitive effects of pregabalin are often temporary and can resolve with a dose reduction or discontinuation of the medication. The effects may be most pronounced at the start of treatment and can improve over time.

Pregabalin and gabapentin both affect the CNS and can cause similar cognitive side effects like dizziness, confusion, and drowsiness. While there are similarities due to their shared mechanism, the incidence and severity of side effects can vary between the two drugs and between individuals.