Fosamax Mental Health and Mood Impact: What the Evidence Actually Shows

What the label lists

The label's most common reactions, in 3% or more of patients, are all gastrointestinal or musculoskeletal: abdominal pain, acid regurgitation, constipation, diarrhea, dyspepsia, musculoskeletal pain and nausea [1]. None of them is a mood, anxiety or cognitive reaction.

In the three-year studies (10 mg daily, n=196, versus placebo, n=397), the Nervous System/Psychiatric entries in the label's table were headache, 2.6% versus 1.5%, and dizziness, 0.0% versus 1.0% [1]. In the FIT clinical fracture cohort (n=3,236 versus 3,223), headache was 0.2% in both groups and dizziness 0.0% versus 0.1% [1]. These tables list reactions the investigators considered drug related in at least 1% of patients [1].

What the fracture trials recorded

FIT enrolled 2,027 postmenopausal women with at least one existing vertebral fracture, randomized to placebo or alendronate (5 mg daily, raised to 10 mg daily at 24 months) for 36 months [2]. New morphometric vertebral fractures occurred in 8.0% versus 15.0% on placebo [2]. The investigators reported no significant difference between groups in numbers of adverse experiences, including upper-gastrointestinal disorders [2].

FLEX randomized 1,099 women who had taken alendronate for a mean of five years to continue or switch to placebo for five more years [4]. Its reported outcomes were bone density, bone turnover markers and fracture [4]. Because the reported outcomes of both trials were bone and fracture measures, they do not settle whether alendronate has any effect on mood [4][2].

Pain as a labeled reaction

Musculoskeletal pain was drug-related in 4.1% on 10 mg daily versus 2.5% on placebo in the two three-year studies [1]. Post-marketing reports describe severe bone, joint or muscle pain with onset from one day to several months; most patients improved after stopping, and some had symptoms return when rechallenged [1]. The label says to discontinue use if severe symptoms develop, and notes that in placebo-controlled trials the percentages with these symptoms were similar to placebo [1].

The FDA's adverse-event dashboard states that a report does not establish that the drug caused the event and cannot be used to estimate how often an event occurs [6].

Where the label addresses mental function

The label says the risk of severe esophageal reactions appears greater when Fosamax is taken without a full 6 to 8 ounces of water or when a patient lies down after dosing, and that Fosamax should not be taken at bedtime [1]. Within that warning, the label says that in patients who cannot comply with dosing instructions because of mental disability, therapy should be used under appropriate supervision [1].

Depression is not among the label's contraindications, which are esophageal abnormalities that delay emptying, inability to sit or stand upright for 30 minutes, hypocalcemia and hypersensitivity to any component [1].