Need help or have questions about your order? Call 510-991-8265Questions about your order? Call 510-991-8265

Sign InShop GLPs
Shop GLPs

Reclast (Zoledronic Acid) Mental Health and Mood Impact

By
Published Updated Last reviewed
6 linked public sourcesEditorial, sourcing, and corrections policy

At a glance

  • Drug / zoledronic acid 5 mg IV once yearly (Reclast) for osteoporosis [4]
  • Mood events in the Reclast osteoporosis adverse reaction table (2% or more) / none listed [4]
  • Nervous-system reactions in that table (Study 1) / headache 12.4% vs 8.1%, dizziness 7.6% vs 6.7% [4]
  • First-infusion acute-phase reaction / 42.4% vs 11.7%, median 3 days, 90% mild or moderate [3]

Does zoledronic acid cause depression or mood changes?

The Reclast osteoporosis table lists adverse reactions reported in at least 2% of patients and more often than placebo in either trial. Among nervous-system reactions, Study 1 (7,736 women) showed headache (12.4% vs 8.1%) and dizziness (7.6% vs 6.7%) [4]. No mood event is in that table [4]. A short-lived reaction after infusion can include fever, aches and fatigue. The label lists fever 18%, myalgia 9%, flu-like symptoms 8%, headache 7% and arthralgia 7%, mostly in the first 3 days and usually resolving within 3 days (up to 7 to 14 days), decreasing with later doses [4]. An analysis found the reaction within 3 days of the first infusion in 42.4% on zoledronic acid versus 11.7% on placebo; median 3 days, 90% mild or moderate [3].

What about anxiety, insomnia and confusion?

A separate label covers the 4 mg cancer dose, not Reclast. In its hypercalcemia of malignancy trial, 86 patients received zoledronic acid 4 mg as a 5-minute infusion and 103 received pamidronate 90 mg over 2 hours. Tabulated nervous-system events, listed regardless of presumed causality, were insomnia 15% vs 10%, anxiety 14% vs 8%, confusion 13% vs 13% and agitation 13% vs 8% [5]. These patients had advanced cancer and high blood calcium. For multiple myeloma or bone metastases, the 4 mg dose is given every 3 to 4 weeks; hypercalcemia of malignancy is treated with a single dose, with retreatment possible after at least 7 days [5]. Reclast for osteoporosis is 5 mg once a year [4].

What eases the post-infusion symptoms?

The Reclast label says patients must be appropriately hydrated before the infusion and that acetaminophen after Reclast administration may reduce acute-phase symptoms [4]. In a trial of 481 postmenopausal women with osteopenia, 409 received zoledronic acid 5 mg with acetaminophen, ibuprofen or placebo; 72 received placebo only [6]. Acetaminophen or ibuprofen every 6 hours for 3 days starting 4 hours after infusion lowered the proportion of women with a raised oral temperature to about 37% versus 63.5% on placebo, and the proportion with worsening symptom scores to 46.3% to 48.5% versus 75.9% [6]. The label advises caution with potentially nephrotoxic drugs such as NSAIDs [4].

Frequently asked questions

Does Reclast cause depression?
Depression does not appear in the Reclast label's table of adverse reactions reported at 2% or more in the osteoporosis trials. The nervous-system reactions in Study 1 were headache (12.4% vs 8.1%) and dizziness (7.6% vs 6.7%) [4].
How long do symptoms after a Reclast infusion last?
The Reclast label says most acute-phase symptoms appear within the first 3 days and usually resolve within 3 days, though they can last 7 to 14 days; they decrease with later doses [4]. An analysis found a median duration of 3 days, with 90% rated mild or moderate [3].
Is anxiety linked to zoledronic acid?
The anxiety rate reported in the 4 mg cancer-dose label was 14% with zoledronic acid versus 8% with pamidronate in the hypercalcemia trial; events were listed regardless of presumed causality [5]. Those patients had advanced cancer and high blood calcium; the 4 mg regimen is not the osteoporosis dose [5].
Can I take an antidepressant with Reclast?
The Reclast label's interaction section lists aminoglycosides, loop diuretics, nephrotoxic drugs such as NSAIDs, and drugs primarily excreted by the kidney. It states that no in vivo drug interaction studies were performed, that zoledronic acid is not metabolized, and that it does not inhibit human CYP450 enzymes in vitro [4]. That section does not name antidepressants.

References

  1. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356(18):1809-22. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis
  2. Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357(18):1799-809. Zoledronic acid and clinical fractures and mortality after hip fracture
  3. Reid IR, Gamble GD, Mesenbrink P, Lakatos P, Black DM. Characterization of and risk factors for the acute-phase response after zoledronic acid. J Clin Endocrinol Metab. 2010;95(9):4380-7. Characterization of and risk factors for the acute-phase response after zoledronic acid
  4. U.S. National Library of Medicine, DailyMed. Reclast (zoledronic acid) injection 5 mg/100 mL prescribing information. Reclast (zoledronic acid) injection 5 mg/100 mL label
  5. U.S. National Library of Medicine, DailyMed. Zoledronic acid injection 4 mg/5 mL (Accord generic, Zometa-type oncology label) prescribing information. Zoledronic acid injection 4 mg/5 mL (Accord generic, Zometa-type oncology label) label
  6. Wark JD, Bensen W, Recknor C, Ryabitseva O, Chiodo J, Mesenbrink P, et al. Treatment with acetaminophen/paracetamol or ibuprofen alleviates post-dose symptoms related to intravenous infusion with zoledronic acid 5 mg. Osteoporos Int. 2012;23(2):503-12. Treatment with acetaminophen/paracetamol or ibuprofen alleviates post-dose symptoms related to intravenous infusion with zoledronic acid 5 mg
Evidence overview for zoledronic acid: Reclast (Zoledronic Acid) Mental Health and Mood Impact