Antidementia Drugs May Increase Risk of Pneumonia

Patients with Alzheimer’s disease undergoing monotherapy with memantine have a higher risk of pneumonia than patients using donepezil, according to research published in the Annals of Medicine.

Investigators from Finland and Sweden used data from the MEDALZ (Medicine use and Alzheimer’s disease) cohort of community-dwelling people with Alzheimer’s disease to examine the link between antidementia drug use and pneumonia.

Eligible persons underwent monotherapy with either an acetylcholinesterase inhibitor (AChEI) or memantine (n=65,481). The most commonly used antidementia drug was donepezil (40.3%), followed by rivastigmine (26.1%), memantine (16.8%) and galantamine (16.7%). On average, donepezil was initiated 139 days after Alzheimer’s diagnosis; rivastigmine, galantamine, and memantine were initiated 131 days, 127 days, and 165 days post-diagnosis, respectively.

Median follow-up time was 402 days (interquartile range [IQR]: 150-806), with 5095 cases of incident pneumonia (8.4% of study population). Mean time from start of medication therapy to pneumonia diagnosis was 584 days, 518 days, 654 days, and 556 days, for donepezil, rivastigmine, galantamine, and memantine, respectively. 

Ultimately, pneumonia risk was highest in patients using a rivastigmine patch (adjusted hazard ratio [aHR]: 1.15; 95% confidence interval [CI], 1.04-1.27) and memantine (aHR: 1.59; 95% CI, 1.48-1.71) vs those using oral rivastigmine (aHR: 1.08; 95% CI, 0.98-1.19) and galantamine (aHR: 0.91; 95% CI, 0.83-1.00), which were not associated with an increased pneumonia risk.

“The risk of pneumonia among those who used memantine monotherapy was 1.6 times higher than the risk of those on donepezil,” the researchers noted. “Memantine is well-tolerated and has fewer adverse effects than AChEIs, so it is likely that the drug itself is not associated with increased pneumonia risk.”

“Use of memantine is associated with disease severity, and therefore the increased risk of pneumonia may be due to more advanced stages of dementia,” concluded the researchers.

Study Limitations

• Researchers did not have data regarding the severity of patients’ Alzheimer’s disease or behavioral and psychological symptoms of dementia.
• Additionally, the researchers did not have data on patients’ lifestyle factors—including smoking status—or frailty status.

Disclosures

Drs Taipale and Tanskanen report participating in research projects funded by Janssen, with grants paid to the institution where they were employed. Dr Tiihonen reports serving as a consultant at Lundbeck, Organon, Janssen-Cilag, Eli Lilly, AstraZeneca, F. Hoffman-La Roche, and Bristol-Myers Squibb, and has received fees for providing expert opinions at Bristol-Myers Squibb and GlaxoSmithKline, as well as lecture fees from Janssen-Cilag, Bristol-Myers Squibb, Eli Lilly, Pfizer, Lundbeck, GlaxoSmithKline, AstraZeneca, and Novartis, and a grant from the Stanley Foundation. Dr Tiihonen is also an advisory board member at AstraZeneca, Janssen-Cilag, and Otsuka. Dr Hartikainen reports receiving a lecture grant from MSD.

Reference

Lampela P, Tolppanen A, Tanskanen A, et al. Use of antidementia drugs and risk of pneumonia in older persons with Alzheimer’s disease. Ann Med. 2016. doi: 10.1080/07853890.2016.1254349