Lithium

What it is

Lithium is a naturally occurring alkali metal, element number 3, given as a salt — usually lithium carbonate, sometimes lithium citrate. The active agent is the lithium ion itself, not a designed molecule. It distributes through total body water, is cleared almost entirely by the kidneys in proportion to its blood level, and has a half-life of about 24 hours. Lithobid is an extended-release tablet containing 300 mg of lithium carbonate.

What the research says

Lithium is the oldest mood stabiliser and still the one with the most consistent long-term randomised evidence. A meta-analysis of 7 placebo-controlled trials found it cut overall mood episodes by about a third, with a clear effect on mania and an equivocal one on depression. A separate meta-analysis of 48 trials found fewer completed suicides on lithium than placebo, though the largest single randomised trial since then, in 519 US veterans, was stopped for futility and found no difference. The costs are real and measurable: the toxic blood level sits close to the therapeutic one, long-term use raises hypothyroidism nearly sixfold and reliably impairs the kidney's ability to concentrate urine, and first-trimester exposure is associated with a dose-related rise in cardiac malformations — smaller than the figure that circulated for decades, but real.

Evidence grade: Well established.

How it works

Drug class: Mood stabiliser (alkali metal ion; no formal pharmacological class)

Lithium is an ion closely related to sodium, and it takes sodium's place in some of the body's transport systems. In nerve and muscle cells it alters how sodium moves and shifts how the brain handles catecholamines such as noradrenaline and dopamine. The label is explicit that the precise biochemical reason it works in mania is still not known. (Source 1)

Boxed warning

Lithium toxicity is closely related to serum lithium levels, and can occur at doses close to therapeutic levels. Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy (see

(Source 2)

What it is used for

• This is the primary approved indication. The label states a manic episode may normalise within 1 to 3 weeks of starting lithium. The strongest randomised evidence for lithium is in prevention rather than acute treatment; the maintenance meta-analysis found the clearest effect on manic episodes. Evidence: established. (Source 3)
• A 2014 systematic review and meta-analysis of 7 placebo-controlled trials (1,580 participants) found lithium reduced overall mood episodes (RR 0.66, 95% CI 0.53 to 0.82) and manic episodes (RR 0.52, 0.38 to 0.71). The effect on depressive episodes depended on the analysis chosen and was not significant under random effects (RR 0.78, 0.59 to 1.03). Evidence: established. (Source 4)
• A 2013 meta-analysis of 48 randomised trials found fewer suicides on lithium than placebo (OR 0.13, 0.03 to 0.66) and fewer deaths from any cause (0.38, 0.15 to 0.95), on very small event numbers. A 2022 randomised trial in 519 US veterans who had recently survived a suicide-related event was stopped for futility, with a hazard ratio of 1.10 (0.77-1.55). The two bodies of evidence point different ways. Evidence: disputed. (Source 5)
• A 2014 meta-analysis of 9 placebo-controlled trials with only 237 patients in total found adding lithium roughly tripled the odds of response (OR 2.89, 95% CI 1.65 to 5.05, p=0.0002) with no heterogeneity, and worked with both tricyclics and newer antidepressants. The authors themselves flag the small size and small number of trials as the main limitation. Evidence: limited. (Source 6)

Interactions

• NSAIDs including COX-2 inhibitors (indomethacin, piroxicam, celecoxib) (pharmacokinetic study): NSAIDs reduce how fast the kidney clears lithium, raising the blood level. In a study in healthy subjects, celecoxib 200 mg twice daily raised steady-state lithium levels by about 17%. (Source 7)
• Thiazide diuretics (hydrochlorothiazide) (pharmacokinetic study): Thiazides make the kidney hold on to lithium. In a double-blind placebo-controlled crossover study in 13 healthy men, serum lithium after five days of hydrochlorothiazide was significantly higher than after furosemide or placebo. (Source 8)
• Diuretics, ACE inhibitors and ARBs (label): All three cause the body to lose sodium, and losing sodium makes the kidney retain lithium, pushing the blood level up toward the toxic range. (Source 9)
• Caffeine and other xanthines (label): Caffeine is a xanthine, and xanthines increase urinary lithium excretion, so they lower the lithium level. The practical risk runs the other way: cutting caffeine suddenly can push the level up. (Source 9)
• Caffeine (clinical literature) (case reports): A 2021 systematic review of 17 studies in bipolar disorder found most of the evidence is case reports; one interventional study found caffeine may suppress lithium concentrations, and several case reports describe lithium levels rising after people cut caffeine down. (Source 10)
• Dietary salt and fluid (label): Lithium competes with sodium in the kidney. A low-salt diet, heavy sweating, diarrhoea or a feverish illness all reduce sodium and fluid and push the lithium level up. The label asks for a normal diet including salt and 2500 to 3500 mL of fluid at least during initial stabilisation. (Source 11)
• St John's wort and other serotonergic agents (label): Lithium can precipitate serotonin syndrome, and the label names St John's Wort among the serotonergic agents that raise that risk alongside SSRIs, SNRIs, triptans, tricyclics, tramadol, fentanyl, tryptophan and buspirone. (Source 12)
• Iodine and potassium iodide supplements (label): Taking iodide preparations, especially potassium iodide, over an extended period together with lithium may produce hypothyroidism — on top of lithium's own thyroid effect. (Source 9)
• Calcium channel blockers (label): Taking them with lithium may raise the risk of neurotoxicity — unsteadiness, tremor, nausea, vomiting, diarrhoea or ringing in the ears. (Source 9)
• Metronidazole (label): Metronidazole reduces renal clearance of lithium and may provoke lithium toxicity. (Source 7)
• Alcohol (label): The US label for Lithobid does not list a specific alcohol interaction. It does warn that lithium may impair mental or physical abilities and that patients should be cautious about activities requiring alertness; alcohol would add to that impairment. We found no pharmacokinetic study of alcohol and lithium in the searches we ran. (Source 7)

Stopping it

• Stopping lithium after stable maintenance is followed by rapid recurrence, and mania comes back about five times sooner than depression. In an analysis of 14 studies and 257 people with bipolar I disorder, more than half of new episodes happened within 10 weeks of stopping. (Source 13)
• The recurrence risk after discontinuation appears to exceed what the untreated course of the illness would predict — the basis for the clinical concern about rebound mania. (Source 13)
• Some lithium effects do not reverse on stopping. The label records reports of nephrogenic diabetes insipidus, hyperparathyroidism and hypothyroidism persisting after discontinuation, and of neurological sequelae that persist and may be associated with cerebellar atrophy. (Source 14)
• Short-term interruption is also how early toxicity is handled: the label says early toxic symptoms can usually be treated by reducing or stopping the dose and restarting lower after 24 to 48 hours. (Source 15)

What goes wrong

Long-term lithium is associated with a near-sixfold higher prevalence of clinical hypothyroidism and a 15% loss of urinary concentrating ability, but end-stage renal failure is uncommon. (Source 16)

• Systematic review, Moderate certainty.
• Size: 5,988 abstracts screened, 385 studies included.
• Who: Patients with mood disorders given lithium, across randomised trials, cohorts, case-control studies and case reports.
• How long: Varied; includes long-term therapy.
• Result: Hypothyroidism OR 5·78 (95% CI 2·00-16·67; p=0·001); urinary concentrating ability reduced by 15% of normal maximum; GFR reduced by -6·22 mL/min (95% CI -14·65 to 2·20, p=0·148); 18 of 3369 (0·5%) received renal replacement therapy.
• Funding: National Institute for Health Research Programme Grant for Applied Research.

Limit of this finding: One number in this review cannot be used as printed. It reports thyroid stimulating hormone rising on average by 4·00 iU/mL with a 95% confidence interval of 3·90-4·10. TSH is not measured in iU/mL (the usual unit is mIU/L), and an interval that narrow around a pooled mean that large is not plausible. Read the direction - lithium raises TSH and raises the rate of clinical hypothyroidism - and do not attach any clinical meaning to the figure 4·00. The review's other figures, including the hypothyroidism odds ratio and the kidney results, are internally consistent. Note also that this abstract uses middle dots as decimal points, so 5·78 means 5.78.

On average, glomerular filtration rate was reduced by -6·22 mL/min (95% CI -14·65 to 2·20, p=0·148) and urinary concentrating ability by 15% of normal maximum (weighted mean difference -158·43 mOsm/kg, 95% CI -229·78 to -87·07, p<0·0001). Lithium might increase risk of renal failure, but the absolute risk was small (18 of 3369 [0·5%] patients received renal replacement therapy). The prevalence of clinical hypothyroidism was increased in patients taking lithium compared with those given placebo (odds ratio [OR] 5·78, 95% CI 2·00-16·67; p=0·001)

Lithium is also associated with raised blood calcium and parathyroid hormone, and with weight gain compared with placebo. (Source 16)

• Systematic review, Moderate certainty.
• Size: 385 studies.
• Who: Patients with mood disorders given lithium.
• How long: Varied.
• Result: Calcium +0·09 mmol/L (95% CI 0·02-0·17, p=0·009); parathyroid hormone +7·32 pg/mL (3·42-11·23, p<0·0001); weight gain versus placebo OR 1·89 (1·27-2·82, p=0·002)
• Funding: National Institute for Health Research Programme Grant for Applied Research.

Limit of this finding: One number in this review cannot be used as printed. It reports thyroid stimulating hormone rising on average by 4·00 iU/mL with a 95% confidence interval of 3·90-4·10. TSH is not measured in iU/mL (the usual unit is mIU/L), and an interval that narrow around a pooled mean that large is not plausible. Read the direction - lithium raises TSH and raises the rate of clinical hypothyroidism - and do not attach any clinical meaning to the figure 4·00. The review's other figures, including the hypothyroidism odds ratio and the kidney results, are internally consistent. Note also that this abstract uses middle dots as decimal points, so 5·78 means 5.78.

Lithium treatment was associated with increased blood calcium (+0·09 mmol/L, 95% CI 0·02-0·17, p=0·009), and parathyroid hormone (+7·32 pg/mL, 3·42-11·23, p<0·0001). Patients receiving lithium gained more weight than did those receiving placebo (OR 1·89, 1·27-2·82, p=0·002)

First-trimester lithium exposure was associated with a dose-related increase in cardiac malformations, but the absolute risk was far smaller than the figure long quoted. (Source 17)

• Cohort study, Low certainty.
• Size: 1,325,563 pregnancies; 663 lithium-exposed infants.
• Who: US Medicaid-enrolled women delivering a live-born infant 2000-2010.
• How long: First-trimester exposure, malformations at birth.
• Result: Cardiac malformations 2.41% (16/663) lithium-exposed versus 1.15% (15,251/1,322,955) unexposed; adjusted RR 1.65 (95% CI 1.02 to 2.68); dose-related: 1.11 (0.46-2.64) at ≤600 mg/day, 1.60 (0.67-3.80) at 601-900 mg, 3.22 (1.47-7.02) above 900 mg; right ventricular outflow tract obstruction defects 0.60% versus 0.18%, adjusted RR 2.66 (1.00-7.06)
• Funding: National Institute of Mental Health.

Cardiac malformations were present in 16 of the 663 infants exposed to lithium (2.41%), 15,251 of the 1,322,955 nonexposed infants (1.15%), and 27 of the 1945 infants exposed to lamotrigine (1.39%). The adjusted risk ratio for cardiac malformations among infants exposed to lithium as compared with unexposed infants was 1.65 (95% confidence interval [CI], 1.02 to 2.68).

Stopping lithium is followed by early recurrence of bipolar illness, especially mania, sooner than the untreated course of the illness would predict. (Source 13)

• Systematic review, Low certainty.
• Size: 14 studies, 257 patients with bipolar I disorder; survival analysis of 124 cases.
• Who: People with bipolar I disorder who discontinued stable maintenance lithium after an average of 30 months.
• How long: Follow-up after discontinuation.
• Result: More than 50% of new episodes within 10 weeks of stopping; computed time to 50% failure of remission 5.0 months; time to 25% recurrence 2.7 months for mania versus 14 months for depression.
• Funding: not stated in the abstract.

Risk of early recurrence of bipolar illness, especially of mania, evidently is increased following discontinuation of lithium use and may exceed that predicted by the course of the untreated disorder.

The gap between the therapeutic and the toxic blood level is narrow, and some people show toxic signs at levels inside the therapeutic range. (Source 14)

• Official position, Certainty not rated.
• Size: Not applicable: regulator-approved labelling.
• Who: People taking lithium carbonate.
• How long: Any.
• Result: Toxic concentrations ≥1.5 mEq/L against a therapeutic range of 0.8 to 1.2 mEq/L; severe manifestations listed include clonus, confusion, seizure, coma and death.
• Funding: not applicable.

The toxic concentrations for lithium (≥1.5 mEq/L) are close to the therapeutic range (0.8 to 1.2 mEq/L). Some patients abnormally sensitive to lithium may exhibit toxic signs at serum concentrations that are considered within the therapeutic range

Chronic lithium can reduce the kidney's ability to concentrate urine, sometimes presenting as nephrogenic diabetes insipidus, which sets up a vicious circle with dehydration and toxicity. (Source 18)

• Official position, Certainty not rated.
• Size: Not applicable: regulator-approved labelling.
• Who: People on chronic lithium therapy.
• How long: Chronic therapy.
• Result: No rate given in the label; usually reversible on stopping.
• Funding: not applicable.

Chronic lithium therapy may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia. Such patients should be carefully managed to avoid dehydration with resulting lithium retention and toxicity. This condition is usually reversible when lithium is discontinued.

Fine hand tremor, excessive urination and thirst are common from the start of treatment and may persist throughout. (Source 19)

• Official position, Certainty not rated.
• Size: Not applicable: regulator-approved labelling.
• Who: People taking lithium.
• How long: From initial therapy onward.
• Result: No percentages given; the label ties severity to serum concentration.
• Funding: not applicable.

Limit of this finding: The label's own concentration bands overlap. It says mild to moderate reactions may occur at 1.5 to 2.5 mEq/L and moderate to severe reactions at 2.0 mEq/L and above, so a level between 2.0 and 2.5 mEq/L falls inside both bands at once and the label does not say which wins. Do not read these bands as a precise severity scale. What they do support is the direction: harm becomes more likely and more severe as the blood level rises, and the label says the level should not be allowed to exceed 2.0 mEq/L during acute treatment.

Fine hand tremor, polyuria, and mild thirst may occur during initial therapy for the acute manic phase and may persist throughout treatment. Transient and mild nausea and general discomfort may also appear during the first few days of lithium administration.

What the evidence supports

Lithium prevented recurrence of mood episodes in bipolar disorder compared with placebo, with the clearest effect on mania. (Source 4)

• Meta-analysis, Moderate certainty.
• Size: 7 placebo-controlled trials, 1,580 participants (plus 7 trials, n=1,305, versus anticonvulsants)
• Who: People with bipolar disorder in long-term treatment intended to prevent mood episodes.
• How long: Long-term maintenance trials.
• Result: Overall mood episodes RR 0.66 (95% CI 0.53 to 0.82); manic episodes RR 0.52 (0.38 to 0.71); study completion RR 1.69 (1.12 to 2.55)
• Funding: not stated in the abstract.

Lithium was more effective than placebo in preventing overall mood episodes (random effects RR 0.66, 95% CI 0.53 to 0.82), manic episodes (random effects RR 0.52, 95% CI 0.38 to 0.71), and, dependent on the type of analyses applied, depressive episodes (random effects RR 0.78, 95% CI 0.59 to 1.03; fixed effect RR 0.73, 95% CI 0.60 to 0.88).

Across 48 randomised trials, fewer people on lithium died by suicide or from any cause than on placebo, though self-harm did not separate. (Source 5)

• Meta-analysis, Low certainty.
• Size: 48 randomised controlled trials, 6,674 participants, 15 comparisons.
• Who: People with unipolar and bipolar mood disorders in long-term treatment.
• How long: Long-term treatment trials up to January 2013.
• Result: Suicides OR 0.13 (95% CI 0.03 to 0.66); all-cause death OR 0.38 (0.15 to 0.95); deliberate self harm OR 0.60 (0.27 to 1.32), not significant.
• Funding: not stated in the abstract.

Lithium was more effective than placebo in reducing the number of suicides (odds ratio 0.13, 95% confidence interval 0.03 to 0.66) and deaths from any cause (0.38, 0.15 to 0.95). No clear benefits were observed for lithium compared with placebo in preventing deliberate self harm (0.60, 0.27 to 1.32).

Adding lithium to an antidepressant in unipolar major depression increased the odds of response, on a small evidence base. (Source 6)

• Meta-analysis, Low certainty.
• Size: 9 randomised placebo-controlled trials, 237 patients in total.
• Who: Adults with unipolar major depression on a tricyclic or second-generation antidepressant.
• How long: Not stated in the abstract.
• Result: OR for response 2.89 (95% CI 1.65, 5.05, z=3.72, p=0.0002); heterogeneity I2=0%; discontinuation for adverse events did not differ from placebo.
• Funding: not stated in the abstract.

The odds ratio for response to lithium vs. placebo in all contrasts combined was 2.89 (95% CI 1.65, 5.05, z=3.72, p=0.0002). Heterogeneity was very low, I(2)=0%.

What the evidence does not support

Lithium's effect on preventing depressive episodes in bipolar disorder was not statistically significant under a random-effects analysis, and it caused more drop-outs for reasons other than a mood episode. (Source 4)

• Meta-analysis, Moderate certainty.
• Size: 7 placebo-controlled trials, 1,580 participants.
• Who: People with bipolar disorder in maintenance treatment.
• How long: Long-term maintenance trials.
• Result: Depressive episodes random effects RR 0.78 (95% CI 0.59 to 1.03); drop-outs for reasons other than a mood episode RR 1.33 (1.07 to 1.65)
• Funding: not stated in the abstract.

Lithium was inferior to placebo in leading to drop-outs for reasons other than a mood episode (random effects RR 1.33, 95% CI 1.07 to 1.65)

The largest randomised trial of lithium for suicide prevention was stopped for futility: adding lithium to usual care did not reduce repeat suicide-related events. (Source 20)

• Randomized trial, Moderate certainty.
• Size: 519 veterans randomised (255 lithium, 264 placebo)
• Who: US veterans with bipolar disorder or depression who had survived a suicide-related event within 6 months; mean age 42.8, 84.2% male.
• How long: Trial stopped early for futility.
• Result: Hazard ratio 1.10 (95% CI 0.77-1.55); 65 suicide-related outcomes on lithium versus 62 on placebo; mean lithium 0.54 mEq/L (bipolar) and 0.46 mEq/L (MDD)
• Funding: US Department of Veterans Affairs cooperative study (NCT01928446); funding not stated in the abstract.

No overall difference in repeated suicide-related events between treatments was found (hazard ratio, 1.10; 95% CI, 0.77-1.55).

The same systematic review found no significant increase in congenital malformations, alopecia or skin disorders, and concluded clinically significant loss of renal function is uncommon. (Source 16)

• Systematic review, Low certainty.
• Size: 385 studies.
• Who: Patients with mood disorders given lithium.
• How long: Varied.
• Result: No significant increased risk recorded for congenital malformations, alopecia or skin disorders; risk of end-stage renal failure described as low.
• Funding: National Institute for Health Research Programme Grant for Applied Research.

Limit of this finding: One number in this review cannot be used as printed. It reports thyroid stimulating hormone rising on average by 4·00 iU/mL with a 95% confidence interval of 3·90-4·10. TSH is not measured in iU/mL (the usual unit is mIU/L), and an interval that narrow around a pooled mean that large is not plausible. Read the direction - lithium raises TSH and raises the rate of clinical hypothyroidism - and do not attach any clinical meaning to the figure 4·00. The review's other figures, including the hypothyroidism odds ratio and the kidney results, are internally consistent. Note also that this abstract uses middle dots as decimal points, so 5·78 means 5.78.

We recorded no significant increased risk of congenital malformations, alopecia, or skin disorders.

Where the evidence is mixed

The authors of that cohort state the effect they found was smaller than had been previously postulated. (Source 17)

• Cohort study, Low certainty.
• Size: 1,325,563 pregnancies.
• Who: US Medicaid-enrolled pregnancies 2000-2010.
• How long: First trimester exposure.
• Result: Adjusted RR 1.65 (1.02 to 2.68) for cardiac malformations overall.
• Funding: National Institute of Mental Health.

Maternal use of lithium during the first trimester was associated with an increased risk of cardiac malformations, including Ebstein's anomaly; the magnitude of this effect was smaller than had been previously postulated.

Where the research disagrees

Whether lithium specifically prevents suicide

• Cipriani and colleagues, updated systematic review and meta-analysis (BMJ 2013), meta-analysis of 48 randomised controlled trials, 6,674 participants: Lithium is an effective treatment for reducing the risk of suicide in people with mood disorders. (Source 21)
• Katz and colleagues, VA Cooperative Study randomised clinical trial (JAMA Psychiatry 2022), double-blind placebo-controlled randomised trial in 519 veterans, stopped for futility: the addition of lithium to usual Veterans Affairs mental health care did not reduce the incidence of suicide-related events in veterans with major depression or bipolar disorders who experienced a recent suicide event. (Source 22)

How much lithium damages the kidney in the long run

• McKnight and colleagues, systematic review and meta-analysis (Lancet 2012), systematic review and meta-analysis of 385 studies: There is little evidence for a clinically significant reduction in renal function in most patients, and the risk of end-stage renal failure is low. (Source 23)
• US prescribing information for Lithobid (ANI Pharmaceuticals), SPL dated 24 August 2026, regulator-approved labelling citing morphologic and postmarketing findings: Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy have been reported in patients on chronic lithium therapy. Morphologic changes have also been seen in manic-depressive patients never exposed to lithium. The relationship between renal function and morphologic changes and their association with lithium therapy have not been established. (Source 18)

How much

• Reference intake: There is no reference intake for a prescription medicine; the dose is set by the prescriber against blood levels. The US label for Lithobid (SPL dated 24 August 2026) gives, as a position, about 1800 mg/day for acute mania aiming at a serum lithium of 1.0 to 1.5 mEq/L, and 900 to 1200 mg/day for long-term control aiming at 0.6 to 1.2 mEq/L. In the label's own tables both totals are split into two equal doses taken in the MORNING and at NIGHT, with the Afternoon column left empty; the footnotes add that the same totals can instead be given three times a day. (Source 24)
• Upper limit: The label sets its ceiling as a blood level rather than a dose: as a position, serum lithium concentrations should not be permitted to exceed 2.0 mEq/L during acute treatment, and toxic concentrations begin at 1.5 mEq/L, close to the therapeutic range. (Source 19)
• Studied: In the VA suicide-prevention randomised trial, participants received extended-release lithium carbonate starting at 600 mg/day, reaching mean concentrations of 0.54 mEq/L in bipolar disorder and 0.46 mEq/L in major depressive disorder at 3 months. (Source 25)
• Studied: In the hydrochlorothiazide interaction study, 13 healthy male volunteers took lithium 300 mg twice daily for 6 weeks. (Source 8)

A common belief, and what the research shows

The belief: Lithium in pregnancy carries a huge risk of Ebstein's anomaly — the figure often quoted from the old lithium birth registries was a 400-fold increase.

What the research shows: The large modern cohort found a much smaller effect. In 1,325,563 Medicaid pregnancies, "Cardiac malformations were present in 16 of the 663 infants exposed to lithium (2.41%), 15,251 of the 1,322,955 nonexposed infants (1.15%)", an adjusted risk ratio of 1.65 (95% CI 1.02 to 2.68), and the authors concluded "the magnitude of this effect was smaller than had been previously postulated." The risk was dose-related, concentrated above 900 mg/day. The current US label still states only that "Data from lithium birth registries suggest an increase in cardiac and other anomalies, especially Ebstein's anomaly."

Questions and answers

What is it?

Lithium is a chemical element — the lightest metal, number 3 on the periodic table — given as a salt, usually lithium carbonate. The medicine works because of the lithium ion itself, so it is not a designed drug molecule like most prescriptions. A standard extended-release tablet contains 300 mg of lithium carbonate. (Source 26)

What does it do in the body?

Lithium behaves somewhat like sodium in the body and takes its place in parts of the nerve and muscle transport machinery, and it shifts how brain cells handle catecholamines. Clinically that translates into dampening manic episodes and reducing how often mood episodes recur. The honest answer on mechanism is that it is not known: the label says so outright. (Source 1)

Is it good or bad for you?

Good when it is needed, monitored, and the level is kept in range; dangerous when it is not. Randomised trials show it prevents mood episode recurrence in bipolar disorder (RR 0.66 for any episode). Against that, the toxic level sits just above the therapeutic one, long-term use raises hypothyroidism nearly sixfold, and it reliably impairs the kidney's ability to concentrate urine. It is a drug with a genuinely narrow margin, which is why blood testing is built into using it. (Source 14)

How do you get more of it?

Medicinal lithium is prescription-only and the dose is matched to a blood level, not to an intake. Trace lithium does occur naturally in drinking water and in some plant foods, at doses orders of magnitude below therapeutic ones. Within treatment, several things raise the level of a fixed dose: NSAIDs, thiazide diuretics, ACE inhibitors and ARBs, losing salt or fluid, and stopping caffeine. Lowering the level is the reverse: more sodium, more fluid, xanthines. (Source 9)

If it is harmful, what reduces it?

If the level is too high, the first step is reducing or stopping the dose; early toxicity can usually be managed that way. In severe poisoning there is no antidote and treatment is supportive, with haemodialysis the effective way to remove the ion from a severely toxic patient. Stopping lithium altogether is a separate decision with its own risk, because recurrence comes fast. (Source 14)

Why might someone be low in it or missing it?

Lithium is not a nutrient the body needs, so there is no deficiency state to be in. What people do get is an unintentionally low blood level while still taking the drug: extra dietary salt, a lot of fluid, xanthines such as caffeine, acetazolamide, sodium bicarbonate and SGLT2 inhibitors all push lithium out through the urine. A level that drifts low is a common reason maintenance stops working. (Source 9)

Which whole foods contain it or feed it?

No whole food supplies a therapeutic amount of lithium; trace amounts occur in drinking water, grains and vegetables. The food question that matters for people on lithium is the opposite one — salt and fluid. The label asks for a normal diet including salt and an adequate fluid intake of 2500 to 3500 mL at least during initial stabilisation, because losing sodium or water drives the lithium level up. (Source 11)

What happens if you do not have it?

If you have never needed lithium, nothing: it is not essential to the body. If you have been on it for bipolar disorder and it stops, the illness comes back, and quickly. Pooled data from 14 studies in 257 people with bipolar I disorder found more than half of new episodes within 10 weeks of stopping, with the time to 25% recurrence of mania 5.2 times earlier than for depression. (Source 13)

How can you test for it?

Lithium is one of the few medicines routinely managed by blood level, and the test is reliable if the timing is right: the sample is drawn 8 to 12 hours after the previous dose, when levels are relatively stable. The label is explicit that the number alone is not enough and must be read alongside the clinical picture. Kidney and thyroid function are checked before and during treatment as well. (Source 27)

References

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