What are the neurocognitive effects of naproxen (Nonsteroidal Anti-Inflammatory Drug, NSAID)?

From the Guidelines

Naproxen is not recommended for long-term use in elderly patients due to its potential neurocognitive effects, and alternative pain relievers should be considered to minimize the risk of adverse events 1. Naproxen, a non-steroidal anti-inflammatory drug (NSAID), may have some neurocognitive effects, though they are generally mild and uncommon in most patients. This NSAID primarily works by inhibiting cyclooxygenase enzymes to reduce inflammation and pain, but it can occasionally cause central nervous system side effects. These effects may include headaches, dizziness, drowsiness, confusion, and in rare cases, memory impairment. Elderly patients are particularly susceptible to these neurocognitive effects. The standard dosage of naproxen is typically 250-500 mg twice daily, with a maximum of 1500 mg per day, and these effects are more likely at higher doses or with prolonged use.

Key Considerations

• Neurocognitive effects are more common in elderly patients, and alternative pain relievers should be considered to minimize the risk of adverse events 1.
• The mechanism behind these effects likely involves naproxen's ability to cross the blood-brain barrier and affect prostaglandin synthesis in the brain, which can influence neurotransmission and cerebral blood flow.
• Taking naproxen with food can help reduce some side effects, though this may not specifically prevent neurocognitive issues.

Alternative Pain Relievers

• Acetaminophen is a suitable alternative for pain relief in elderly patients, with a lower risk of adverse events compared to NSAIDs 1.
• Other non-pharmacologic and non-opioid pharmacologic treatments, such as exercise therapy and cognitive-behavioral therapy, can also be effective in managing chronic pain 1.

From the FDA Drug Label

Nervous System: inability to concentrate, depression, dream abnormalities, insomnia, malaise, myalgia, muscle weakness, asepticmeningitis, cognitivedysfunction, convulsions

Nervous System: anxiety, asthenia, confusion, nervousness, paresthesia, somnolence, tremors, convulsions, coma, hallucinations

The neurocognitive effects of naproxen include:

• Cognitive dysfunction
• Inability to concentrate
• Depression
• Confusion
• Anxiety
• Nervousness
• Somnolence These effects are reported in approximately 1% to 10% of patients taking naproxen 2.

From the Research

Neurocognitive Effects of Naproxen

• The effects of naproxen on cognitive function have been studied in several trials, with mixed results 3, 4.
• A randomized, controlled trial of naproxen and celecoxib found that use of naproxen or celecoxib did not improve cognitive function, and there was weak evidence for a detrimental effect of naproxen 3.
• Longitudinal analyses showed lower global summary scores over time for naproxen compared with placebo, and lower scores on the Modified Mini-Mental State Examination over time for both treatment groups compared with placebo 3.
• However, a later study found that naproxen may have a beneficial effect on cognitive function in asymptomatic individuals, with reduced Alzheimer-type neurodegeneration suggested by CSF biomarker assays 4.

Safety and Efficacy of Naproxen

• Naproxen has been found to have a similar safety profile to placebo, with no increased risk of adverse events with short-term use 5.
• The most frequently reported adverse events with naproxen were related to the gastrointestinal system, but there were no differences between groups 5.
• Naproxen has been shown to be effective in reducing pain and swelling in various conditions, including rheumatic diseases, acute gout, and pain following surgery or trauma 6, 7.
• Naproxen is also effective in treating a variety of types of acute pain, including dysmenorrhea, headache, and dental pain 7.

Comparison with Other NSAIDs

• Naproxen has been compared with other non-steroidal anti-inflammatory drugs (NSAIDs), including celecoxib, ibuprofen, and acetaminophen, with similar efficacy and safety profiles 3, 5, 6.
• Naproxen may have a beneficial effect on cognitive function in asymptomatic individuals, whereas other NSAIDs may have an adverse effect in later stages of AD pathogenesis 4.