Proton pump inhibitors, which are sometimes recommended to ease stomach problems during cancer treatment, may have an unintended side effect: impairment of breast cancer survivors' memory and concentration. These findings were published by Madison et al in the Journal of Cancer Survivorship.

Meta-Analysis

The study, the first to look at proton pump inhibitor use in breast cancer survivors, used data from three previous Ohio State clinical trials examining fatigue, a yoga intervention, and vaccine response in patients with breast cancer and survivors. In each of those studies, participants had reported their use of prescribed and over-the-counter medications and rated any cognitive symptoms they had as part of routine data collection.

Data from 551 women in those earlier studies, 88 of whom reported taking proton pump inhibitors, were used in the analysis. The women in the previous studies had provided self-reports of proton pump inhibitor use and cognitive symptoms multiple times over varied periods of time depending on the design of each study.

Findings

After controlling for a variety of factors that could affect cognition—such as depression or other illnesses, types of cancer treatment, age, and education—the researchers found that proton pump inhibitor use predicted more severe concentration and memory symptoms, as well as lower quality of life related to impaired cognition.

Women in the studies had completed a questionnaire rating the severity of their memory and concentration problems on a scale of 0 to 10 over the previous 5 days. The new analysis found that on average, proton pump inhibitor users’ concentration problems in the fatigue study were 20% more severe than those reported by non–proton pump inhibitor users. In the yoga study, proton pump inhibitor users’ concentration problems were 29% more severe than those reported by non–proton pump inhibitor users. There were no differences in reported memory problems.

In the third study, which featured data from the placebo visit of a typhoid vaccine trial, reported memory problems were 28% more severe in proton pump inhibitor users than in nonusers, with no differences in reports of concentration issues. Breast cancer survivors in this study completed an additional questionnaire measuring the functional implications of their cognitive impairment. Proton pump inhibitor users’ scores were lower than nonusers’ scores on this assessment, where proton pump inhibitor users reported a poorer quality of life, greater cognitive impairment, and poorer cognitive abilities compared to nonusers.

“The severity of the cognitive problems reported by proton pump inhibitors users in this study was comparable to what patients undergoing chemotherapy had reported in a large observational study,” said Annelise Madison, lead author of the study and a graduate student in clinical psychology at The Ohio State University. “Proton pump inhibitor nonusers also reported problems, but were definitely getting better. Based on what we're seeing, we don't know if proton pump inhibitors users might not be able to fully recover cognitively after chemotherapy. It's an area for further investigation."

The U.S. Food and Drug Administration has approved proton pump inhibitors for short-term use to treat common gastric acid conditions and longer-term use for gastric ulcers and disorders involving excessive acid secretion. Ms. Madison noted that the off-label maintenance use of proton pump inhibitors in cancer patients can last a long time: the analysis showed that at least two-thirds of the breast cancer survivors using proton pump inhibitors had taken them for between 6 months and 2 years.

The researchers said a clinical trial controlling proton pump inhibitor doses and obtaining objective cognitive data would be required to identify any causal effect.

Disclosure: This work was supported by grants from the National Institutes of Health. For full disclosures of the study authors, visit link.springer.com.