Can Lyrica (pregabalin) cause mental status changes, such as memory impairment and sleepiness, after initiation of therapy?

Pregabalin (Lyrica) Can Cause Mental Status Changes Including Memory Impairment and Somnolence

Yes, Lyrica (pregabalin) can cause mental status changes such as memory impairment and sleepiness beginning with the first dose. These are well-documented adverse effects listed in the FDA drug labeling information.

Common Neurological Side Effects of Pregabalin

Pregabalin is associated with several central nervous system effects that can impact mental status:

• Somnolence/Sleepiness: Occurs in up to 28% of patients taking pregabalin, with higher rates at higher doses 1
• Dizziness: One of the most common side effects, occurring in up to 38% of patients 1
• Memory impairment: Reported in 3-4% of patients taking therapeutic doses 1
• Disturbance in attention: Occurs in approximately 5% of patients 1
• Confusion: Reported in 2-4% of patients, with higher rates at higher doses 1
• Thinking abnormal: Occurs in 8-9% of patients at therapeutic doses 1

Dose-Dependent Relationship

The neurological side effects of pregabalin demonstrate a clear dose-dependent relationship:

• At lower doses (150mg/day), cognitive effects are less pronounced 1
• At higher doses (300-600mg/day), mental status changes become more common and potentially more severe 1
• These effects can begin immediately after the first dose, as pregabalin reaches peak plasma levels approximately 1 hour after oral administration 2

Mechanism of Action and CNS Effects

Pregabalin's mechanism helps explain these cognitive effects:

• Pregabalin binds to alpha2-delta subunits of voltage-gated calcium channels in the central nervous system 3
• This binding reduces the release of several neurotransmitters, which accounts for both its therapeutic effects and its cognitive side effects 3
• The drug has high bioavailability (approximately 90%) and readily crosses the blood-brain barrier, allowing it to quickly affect CNS function 2

Risk Factors for Increased Cognitive Side Effects

Certain patient populations may be at higher risk for experiencing mental status changes:

• Elderly patients 1
• Patients with renal impairment (pregabalin is primarily eliminated unchanged through the kidneys) 1
• Patients taking other CNS depressants concurrently 1
• Patients with hepatic impairment 1

Clinical Management

When mental status changes occur with pregabalin:

• Consider dose reduction if symptoms are troublesome but the medication is providing benefit 1
• Monitor for worsening of symptoms, particularly in elderly patients 1
• Be aware that symptoms typically begin shortly after initiation or dose increase 1
• Recognize that these effects are generally reversible upon dose reduction or discontinuation 4

Comparison to Other Medications

In the context of medications that can cause cognitive impairment:

• Pregabalin's cognitive effects are similar to but often less severe than those of benzodiazepines 5
• Like other CNS depressants, pregabalin can cause delirium, particularly in vulnerable populations 5
• Antipsychotics and benzodiazepines can also cause similar mental status changes and may themselves cause delirium 5

In conclusion, the mental status changes described (memory impairment and sleepiness) are consistent with known side effects of pregabalin that can begin with the first dose and are well-documented in the FDA labeling information.