Lithium

If you take lithium for bipolar disorder or as an add-on treatment for depression, your serum level helps guide dosing. The same dose can produce different levels in different people, and your own level can change after a new prescription, an illness, or poor fluid intake. Your symptoms and kidney, thyroid, and calcium results remain part of the assessment. A reassuring lithium result alone doesn't establish that treatment is effective or free of harmful effects.

Serum lithium is an established test for monitoring prescribed treatment and evaluating suspected poisoning. Research into trace exposure from food, water, and supplements addresses different questions. Routine serum testing has no established role in screening healthy people for a lithium deficiency or measuring biological aging.

What Serum Lithium Measures

Lithium medicines contain salts that release positively charged lithium particles when dissolved. These particles circulate largely unbound to blood proteins. This test measures their concentration in serum from a blood draw. Serum is the liquid remaining after a blood sample clots. Results use mmol/L to describe how much lithium is dissolved in a given volume of serum. For lithium, mmol/L and mEq/L describe the same amount, so results reported either way can be read the same.

Your kidneys remove almost all lithium from your body. They filter it and then return much of the filtered amount to the blood through processes that also handle sodium. Changes in kidney function, fluid balance, and salt intake can therefore change your lithium exposure.

Blood levels take several days to settle into a new pattern after a dose change, typically five to six days and longer in older adults or when kidney function is reduced. Slower elimination is one reason the same dose can become excessive as your health changes.

Serum Exposure and Relapse Protection

A dose-response analysis of six randomized trials involving 975 people with bipolar disorder associated higher serum concentrations with fewer recurring mood episodes. The modeled relationship differed for mania and depression: protection against depression appeared to require greater exposure. These estimates describe patterns across trial groups and don't establish the best concentration for an individual.

Maintenance targets differ by guideline. NICE suggests 0.6 to 0.8 mmol/L for most people, or 0.8 to 1.0 mmol/L after a relapse while on lithium. The US prescribing label gives 0.8 to 1.0 mEq/L for maintenance. The CANMAT and ISBD bipolar guidance uses 0.6 to 1.0 mmol/L. These are recommendations from different bodies, and your own target depends on your response, age, kidney function, and side effects. US obstetric guidance notes that toxicity often appears at 1.5 mEq/L or higher, though chronic buildup can cause toxicity at lower levels.

A Taiwanese cohort of 466 people who were initially stable also found significantly fewer recurrences in the middle concentration group than in the lowest group. The highest group had only 26 people, and its result was inconclusive. Recurrence in that study wasn't a confirmed mood episode. It was counted as a psychiatric admission or any increase or addition of psychiatric medication, and lithium was measured only at the start of follow-up. Because treatment wasn't randomly assigned, differences in illness and prescribing could also have influenced the findings.

Kidney Function Over the Years

Long-term lithium use can impair kidney function, though estimates of risk differ across studies. In a Hong Kong analysis of people with bipolar disorder, lithium use was associated with about a third higher adjusted risk of developing stage 3 or more advanced chronic kidney disease compared with other mood stabilizers. Higher average lithium concentrations were associated with greater risk. The study found no difference in stage 4 or more advanced disease or kidney failure.

A Swedish study of 10,946 people starting lithium or valproate found no clear difference in kidney disease progression between the two treatments. Within the lithium group, concentrations above 1.0 mmol/L were associated with about 3.5 times the risk of acute kidney injury. The estimate for longer-term kidney disease progression in that category was too uncertain to establish a difference.

These observational comparisons don't prove that any particular lithium exposure is harmless. Kidney health, treatment duration, prescribing decisions, and the outcomes being measured differ between studies.

A Dutch cohort followed 196 long-term users for a median of 8.8 years. About three in five lost kidney filtration faster than the average decline reported in the general population, and higher average serum lithium concentrations were associated with faster decline after accounting for age, sex, and treatment duration. This comparison didn't include a matched untreated control group.

Lithium can also reduce the kidneys' ability to concentrate urine. That can cause persistent thirst and unusually large amounts of urine, even before a substantial fall in filtration appears.

Thyroid and Calcium Effects

Lithium can interfere with thyroid hormone release and cause an underactive thyroid. An Oxford laboratory study found about 2.3 times the adjusted risk of hypothyroidism among lithium users. Risk was highest in younger women and in people with above-median lithium levels.

The same study found about 40% more raised total calcium results. That association wasn't statistically established after calcium was adjusted for albumin. Albumin is a blood protein that carries some calcium.

Lithium can also affect the parathyroid glands, which regulate blood calcium. A systematic review estimated overactive parathyroid glands in about 4% of lithium users, compared with about 0.5% in a healthy population. A serum lithium level doesn't diagnose these thyroid or parathyroid complications.

Toxicity Depends on More Than the Number

Lithium poisoning can follow an overdose or a gradual buildup during prescribed treatment. With chronic accumulation, serious effects on the brain can occur at less striking serum concentrations because lithium has already entered tissues. An acute overdose can also be life-threatening, and neurological symptoms may be delayed. The blood concentration and the severity of symptoms don't always move together.

A Swedish study reviewed 91 intoxication episodes in 77 people, with intoxication defined as a level of at least 1.5 mmol/L. There were no deaths, and kidney function after the episodes was similar to baseline on average. But about a third of episodes required intensive care, and some needed dialysis. Those findings don't guarantee recovery without lasting harm in an individual case.

What the Dementia Research Means

In a UK mental health service cohort of 29,618 adults aged 50 or older, lithium exposure was associated with about 44% lower risk of dementia after adjustment for measured differences between groups. Only 548 people had lithium exposure. The study was observational, so differences in prescribing and health could still explain part of the association.

Pooled analyses disagree. A 2026 meta-analysis estimated a lower dementia risk with lithium exposure, while a 2024 meta-analysis of eight observational studies found no significant association, either in the general population or among people with bipolar disorder.

This research concerns treatment exposure. It hasn't validated serum lithium as a test of your dementia risk or established a concentration that prevents dementia in healthy people.

When Results Can Be Misleading

• Timing after a dose: concentrations rise after taking lithium and then fall. Samples collected at different intervals can appear to show a change in exposure even when the dose is unchanged.
• Recent dosing changes: missed doses, extra doses, or a recent change in dose, brand, or formulation can make a result unrepresentative of your usual exposure. A sample drawn before levels have settled can underestimate your eventual exposure.
• The collection tube: a tube containing lithium heparin can contaminate the sample and produce a falsely high result, sometimes in the toxic range. Collection requires a serum tube approved by the performing laboratory.
• Illness and fluid loss: vomiting, diarrhea, fever, and dehydration can cause a real increase in lithium exposure. An unexpected result during illness shouldn't be dismissed as laboratory variation.
• Pregnancy and after delivery: kidney clearance rises during pregnancy and falls back after delivery. Studies disagree on the pattern. Some found the lowest levels in the second trimester with a return toward pre-pregnancy values in the third, while a small Norwegian study found lower levels late in pregnancy. Continuing a pregnancy-adjusted dose after delivery can increase exposure.

Tracking Your Trend

A useful series of results includes the dose, formulation, time of the last dose, collection time, and kidney function. Your prescriptions and health can change while the number of tablets stays the same. Comparing measurements collected under similar conditions helps distinguish a lasting change in exposure from a difference in sampling.