Alendronate therapy associated with depression, anxiety

Via Peters

March 18, 2022

2 min read

The authors report no relevant financial disclosures.

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Compared with other first-line osteoporosis treatments, alendronate therapy yielded an increased risk for depression and anxiety, according to an analysis of adverse events reports.

The findings were published in Scientific Reports.

Alendronate increases risk for anxiety and depression compared with teriparatide

Alendronate therapy is associated with a higher likelihood for depression and anxiety compared with teriparatide. Data were derived from Keshishi D, et al. Sci Rep. 2022;doi:10.1038/s41598-021-03214-x.

According to study background, bisphosphonate therapy, primarily alendronate, is among the most prescribed treatments for osteoporosis, a disease affecting more than 10 million Americans older than 50 years. Recently, case reports have shown alendronate and other bisphosphonates may increase depressive symptoms.

To evaluate these associations, Dro Keshishi, a third-year student at the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego, and colleagues analyzed more than 100,000 adverse events reports from the FDA Adverse Event Reporting System (FAERS) and the WHO’s VigiAccess adverse drug reactions global database.

Outcomes of interest included depression, or depressive disorder-related adverse events, and anxiety, which were defined in FAERS by following Medical Dictionary for Regulatory Activities (MedDRA) terms. Drug therapies studied included alendronate, zoledronate, risedronate, ibandronate, denosumab (Prolia, Amgen) and teriparatide (Forteo, Eli Lilly; Bonsity, Alvogen).

In an analysis of patients aged 65 years or younger, the reported OR with alendronate therapy was 14.67 (95% CI, 11.55-18.63) for depression and 7.1 (95% CI, 5.79-8.71) for anxiety. Among the other therapies, only risedronate demonstrated an elevated OR, although only for depression and at a lower magnitude (3.06; 95% CI, 1.7-5.52), whereas zoledronate (0.167; 95% CI, 0.074-0.38) and denosumab (0.2; 95% CI, 0.1-0.39) were significantly associated with decreased anxiety.

Furthermore, among patients older than 65 years, alendronate was the only therapy associated with increased reported OR for depression (3.6; 95% CI, 2.82-4.59) and anxiety (2.28; 95% CI, 1.84-2.84) compared with the control teriparatide, whereas zoledronate (0.32; 95% CI, 0.21-0.5), ibandronate (0.26; 95% CI, 0.13-0.52) and denosumab (0.26; 95% CI, 0.18-0.36) showed significant decreases in the OR for anxiety.

In the VigiAccess analysis, the bisphosphonates as a class yielded significantly higher reported ORs for depression and anxiety, with alendronate demonstrating the highest magnitude in depression (4.33; 95% CI, 4.09-4.58) and anxiety (3.14; 95% CI, 2.97-3.33).

“We found that alendronate had the largest and statistically significant association with depression and anxiety out of all bisphosphonates,” Keshishi and colleagues concluded. “This association was supported by VigiAccess/WHO analysis. Controlled trials are necessary to adjudicate the clinical causality.”

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