Aim lower in older adults. Here’s the data.
STUDY: Nunes PV et al, Bipolar Disorders 2026
STUDY TYPE: Systematic review
FUNDING: Independent
Background
Expert guidelines recommend lower lithium levels for older adults, such as these ranges for maintenance in bipolar and acute depression in bipolar/unipolar:
- Age 7 into adulthood: 0.6–0.8 mmol/L
- Age 60–79 years: 0.4–0.7 mmol/L
- Age ≥ 80: 0.4–0.6 mmol/L
Part of the reason is theoretical. More lithium passes across the blood brain barrier as we age. This analysis brings together the empiric support.
The Study
- Fourteen observational studies, 8808 older adults with bipolar disorder taking lithium, published since 2017
- No head-to-head dosing trials. Researchers pooled reported serum levels, doses, and outcomes across cohorts.
Results
Across the studies, patients were maintained at mean or median levels of just 0.47-0.67 mmol/L, well under the standard range. Side effects and early toxicity signs showed up starting around 0.82-1.00 mmol/L, and overt toxicity appeared above 1.20-1.25 mmol/L.
Older adults reached these therapeutic levels on daily doses of 450-560 mg, roughly half the typical adult dose of 900-1200 mg.
NSAIDs stood out as the one drug class that independently raised lithium levels, adding about 0.121 mmol/L on average. Each additional interacting medication (ACE inhibitors, diuretics) nudged levels up further. Monitoring was spotty everywhere: in one cohort of 5503 patients, only 24% had a lithium level checked within the recommended 90 days.
Practice Implications
- Aim lower in older adults.
- For all patients, keeping the level below 0.8 reduces renal risk, in some studies to undetectable levels.
- More practical tips on lithium management in Difficult to Treat Depression.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
