In 10,615 older adults on lithium, a new loop diuretic or ACE inhibitor raised toxicity admissions five- to eightfold
Ontario, 1992 to 2001: 413 of 10,615 elderly lithium users (3.9 percent) were admitted for lithium toxicity. Starting a loop diuretic carried a relative risk of 5.5, an ACE inhibitor 7.6. Thiazides and NSAIDs were not independently linked.
Suggestive but preliminary. Not settled. how we score evidence
Caveat on this rating: Wide confidence intervals (the ACE inhibitor interval runs from 2.6 to 22). Adults 66 and older only. Case-control design in administrative data: association, not proof. The NSAID null result conflicts with the label and with pharmacology; the authors report it, they do not explain it.
The lithium label lists four drug classes that raise lithium levels. This study asked which of them actually put older patients in hospital.
Significant findings
Juurlink and colleagues (Journal of the American Geriatrics Society, 2004) ran a population-based nested case-control study of Ontario residents aged 66 and older treated with lithium. "From January 1992 to December 2001, 10,615 elderly patients continuously receiving lithium were identified, of whom 413 (3.9%) were admitted to the hospital at least once for lithium toxicity."
"After adjustment for potential confounders, a dramatically increased risk of lithium toxicity was seen within a month of initiating treatment with a loop diuretic (relative risk (RR)=5.5, 95% confidence interval (CI)=1.9-16.1) or an ACE inhibitor (RR=7.6, 95% CI=2.6-22.0). Conversely, neither thiazide diuretics nor NSAIDs were independently associated with a significantly increased risk of hospitalization for lithium toxicity."
The conclusion: "The use of loop diuretics or ACE inhibitors significantly increases the risk of hospitalization for lithium toxicity, particularly in naïve recipients."
Worth asking
Two readings, both fair. The first: the danger is concentrated in the first month after a loop diuretic such as furosemide or an ACE inhibitor such as lisinopril is started, which is exactly when a lithium level should be checked. The second: the NSAID null result is a population average in a group whose NSAID use was probably brief; it does not license regular ibuprofen on lithium, and the label still says monitor. If you are on lithium and a new heart or blood pressure drug is proposed, the question is whether a lithium level is booked for the weeks after it starts.
Source
Drug-induced lithium toxicity in the elderly: a population-based study — Juurlink DN, Mamdani MM, Kopp A, Rochon PA, Shulman KI, Redelmeier DA (2004)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1111/j.1532-5415.2004.52221.x
DOI: 10.1111/j.1532-5415.2004.52221.x
How this was scored
- Study design
- Case-control study
- Funding
- Funding not disclosed
- Published in
- Reputable peer-reviewed journal
- Sample size
- 10,615
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "early signal". Suggestive but preliminary. Not settled. It scores 50 out of 100 on our published rubric. One caveat travels with that badge: Wide confidence intervals (the ACE inhibitor interval runs from 2.6 to 22). Adults 66 and older only. Case-control design in administrative data: association, not proof. The NSAID null result conflicts with the label and with pharmacology; the authors report it, they do not explain it. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Drug-induced lithium toxicity in the elderly: a population-based study — Juurlink DN, Mamdani MM, Kopp A, Rochon PA, Shulman KI, Redelmeier DA (2004). Published in: Reputable peer-reviewed journal. DOI: 10.1111/j.1532-5415.2004.52221.x. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Case-control study. Funding: Funding not disclosed. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.