From the FDA Drug Label
Other Effects Systemic effects of omeprazole in the CNS, cardiovascular and respiratory systems have not been found to date In a 52-week toxicity study in Sprague-Dawley rats, brain astrocytomas were found in a small number of males that received omeprazole at dose levels of 0.4,2, and 16 mg/kg/day (about 0.1 to 3. 9 times the human dose of 40 mg/day, based on a body surface area basis).
Omeprazole's effect on the brain is not well understood in humans, as there is limited information available. However, in animal studies, brain astrocytomas were found in a small number of male rats that received omeprazole at certain dose levels 1. It is essential to note that these findings may not be directly applicable to humans. In terms of human data, no systemic effects of omeprazole on the CNS have been reported to date 1.
From the Research
Omeprazole use has been associated with significant cognitive impairments, including verbal fluency, short-term episodic memory, selective attention, and executive functions, particularly with long-term treatment. As a proton pump inhibitor (PPI), omeprazole primarily works in the stomach by blocking acid production, not in the central nervous system. However, some patients report side effects like headaches, dizziness, or confusion while taking omeprazole, which may suggest indirect effects on brain function. These neurological side effects are relatively uncommon and typically mild. In rare cases, long-term PPI use has been associated with vitamin B12 deficiency, which could potentially affect neurological function if severe and untreated.
The most recent study on this topic, published in 2024 2, investigated the cognitive impairments associated with long-term omeprazole treatment and found significant group differences in verbal fluency, short-term episodic memory, selective attention, and executive functions. The duration of omeprazole treatment was also positively associated with the magnitude of cognitive impairment. Another study published in 2021 3 found that omeprazole use was associated with anxiety, hypoactivity, memory deficits, and decreases in brain serotonin and 5-HT-1A receptors expression in rats.
While some studies suggest a possible association between long-term PPI use and increased risk of dementia, the relationship remains controversial and unproven. A review study published in 2018 4 highlighted the potential threat of PPIs, including omeprazole, as a cause of dementia and depression. However, a more recent study published in 2022 5 found that histamine-2 receptor antagonists (H2RAs) were associated with cognitive decline, specifically among people with pre-existing cognitive impairment, compared to PPIs.
Key points to consider:
- Omeprazole use has been associated with cognitive impairments, particularly with long-term treatment 2
- The duration of omeprazole treatment is positively associated with the magnitude of cognitive impairment 2
- Omeprazole use has been linked to anxiety, hypoactivity, memory deficits, and decreases in brain serotonin and 5-HT-1A receptors expression in rats 3
- The relationship between long-term PPI use and increased risk of dementia remains controversial and unproven 4, 5