This page shows what was measured, who it was measured in, and what that does not settle.
What Lithium Carbonate does in the body
Two ideas dominate the research literature: that it blocks an enzyme called glycogen synthase kinase-3, and that it depletes a signalling molecule called inositol.
Nobody knows. That is not a simplification for a general reader — it is what the approved label says in the mechanism section. Lithium is a small positively charged atom, close in size to sodium and potassium, and it spreads through the water in the body and eventually into the brain. Neither has been established well enough to appear in the label. What is established is that it works, that the amount that works is close to the amount that poisons, and that the difference between the two is measured with a blood test.
Why people take it. The manic phase of bipolar disorder, and long-term prevention of further episodes
What happened in people
A hazard ratio of 0.71 (95% CI 0.51 to 1.00, p=0.0472) against valproate for a new intervention for an emergent mood episode over up to two years
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
NCT01928446 — Li+ plus, lithium versus placebo for repeat suicide-related outcomes (NCT01928446) · a recorded source, not a stored snapshot
The limit that matters most
The only drug on this page requiring a blood test to be used safely, and the only one whose toxic range abuts its therapeutic range
Where it acts
No identified site of action. Lithium distributes through total body water as a small cation and takes up to 24 hours to reach brain tissue; the kidney, thyroid and parathyroid are where its long-term effects are measured.
Kind of result
Symptoms and quality of life
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 2BMD2GNA4V · read 2026-08-29
The supplement label database classes it as mineral, under the name Lithium.
US prescribing information · d3284649-ed4c-4096-987b-4ac16b8278f2 · read 2026-08-30
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 161 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Time to the first repeated suicide-related event — repeated suicide attempt, interrupted attempt, hospitalisation to prevent suicide, or death from suicide — in veterans with bipolar disorder or depression who had survived a recent suicide-related event
✗ The study did not show it
Who was studied
NCT01928446 (Li+ plus)
How many people
519
Study design
Double-blind placebo-controlled randomised trial across 29 VA medical centres
Compared against
A dummy treatment
Kind of result
Living longer, or avoiding a major event
What was found
Hazard ratio 1.10 (95% CI 0.77 to 1.55); 65 of 255 on lithium and 62 of 264 on placebo had a suicide-related outcome; trial stopped for futility
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Mean serum concentrations at three months were 0.54 mEq/L in the bipolar group and 0.46 mEq/L in the depression group, below the 0.8 to 1.2 mEq/L range the label states as therapeutic. That limits how far the null result can be generalised to fully dosed treatment.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral immediate-release capsule or tablet, oral solution, and extended-release tablet
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
NCT01928446 — Li+ plus, lithium versus placebo for repeat suicide-related outcomes (NCT01928446) · a recorded source, not a stored snapshot
United States prescribing information for lithium carbonate — Boxed Warning (Lithium Toxicity), sections 5.1, 5.4, 5.5, 5.7, 5.8, Unmasking of Brugada Syndro… · a recorded source, not a stored snapshot
Initiation of a new intervention for an emergent mood episode in bipolar I disorder, comparing lithium, valproate and their combination
✓ The study showed what it set out to show
Who was studied
BALANCE (ISRCTN 55261332)
How many people
330
Study design
Randomised open-label trial with masked outcome adjudication, up to 24 months
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Hazard ratios 0.59 (95% CI 0.42 to 0.83, p=0.0023) combination against valproate, 0.71 (95% CI 0.51 to 1.00, p=0.0472) lithium against valproate, and 0.82 (95% CI 0.58 to 1.17, p=0.27) combination against lithium
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The trial was open-label: investigators and participants knew the allocation and only the outcome-adjudicating team was masked, in a trial whose primary endpoint is a clinician's decision to intervene. Sixteen participants had serious adverse events after randomisation, including six deaths across the three arms.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral immediate-release capsule or tablet, oral solution, and extended-release tablet
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
NCT01928446 — Li+ plus, lithium versus placebo for repeat suicide-related outcomes (NCT01928446) · a recorded source, not a stored snapshot
United States prescribing information for lithium carbonate — Boxed Warning (Lithium Toxicity), sections 5.1, 5.4, 5.5, 5.7, 5.8, Unmasking of Brugada Syndro… · a recorded source, not a stored snapshot
What we know
RNAWiki holds 2 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Lithium Carbonate
What a person takes: Oral immediate-release capsule or tablet, oral solution, and extended-release tablet.
The measurement behind this step
There is no injectable and no long-acting depot. Absorption is complete and clearance is entirely renal, in parallel with sodium handling, which is why the interaction list is dominated by non-steroidal anti-inflammatories, ACE inhibitors, angiotensin receptor blockers and thiazide diuretics rather than by other psychiatric drugs. Extended-release forms smooth the peak concentration but do not change the requirement for serum monitoring.
Getting in
A tablet of a mineral salt, taken daily for years or decades
Lithium carbonate is a salt made from an element mined out of rock or pumped from brine. It comes as an ordinary tablet and as an extended-release form.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The salt dissociates in the stomach and what is absorbed is the lithium cation. There is no prodrug step, no metabolite and no hepatic metabolism: the substance that is swallowed is the substance that acts and the substance that is excreted, entirely by the kidney.
NCT01928446 — Li+ plus, lithium versus placebo for repeat suicide-related outcomes (NCT01928446) · a recorded source, not a stored snapshot
Reaching the cell
It spreads through body water and reaches the brain slowly
The lithium ion distributes through the water in the body and takes up to a day to get into brain tissue, which is why the effects of an overdose can appear long after it was taken.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Distribution is through total body water rather than into fat, and the label states lithium may take up to 24 hours to distribute into brain tissue, so acute toxicity symptoms may be delayed. Clearance is renal and is handled in parallel with sodium, which is why dehydration, sodium restriction, thiazide diuretics, ACE inhibitors and non-steroidal anti-inflammatories all raise the serum concentration without any change in the amount taken.
NCT01928446 — Li+ plus, lithium versus placebo for repeat suicide-related outcomes (NCT01928446) · a recorded source, not a stored snapshot
What it acts on
It binds nothing that has been established
This is where every other drug on this page has a receptor. Lithium does not. The approved label states that the mechanism of action as a mood stabilising agent is unknown.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Section 12.1 of the label is a single sentence stating the mechanism is unknown. The leading candidate mechanisms are inhibition of glycogen synthase kinase-3 beta and inhibition of inositol monophosphatase leading to inositol depletion, both plausible at concentrations near the therapeutic range and neither established. Lithium's ionic radius sits close to those of sodium and magnesium, which is the structural basis for the proposal that it competes with magnesium at enzyme active sites.
NCT01928446 — Li+ plus, lithium versus placebo for repeat suicide-related outcomes (NCT01928446) · a recorded source, not a stored snapshot
The change it makes
The kidney, thyroid and parathyroid register it over years
Whatever lithium does in the brain, what it does to the kidneys, thyroid and calcium regulation is measurable and cumulative, and those measurements are the reason people stop taking it.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The label names lithium-induced chronic kidney disease associated with structural changes on chronic therapy, hypothyroidism and hyperthyroidism, and hypercalcaemia and hyperparathyroidism associated with long-term use, each with a monitoring instruction. Renal manifestations of toxicity include urine concentrating defect, nephrogenic diabetes insipidus and renal failure. An encephalopathic syndrome carries increased risk when lithium is combined with an antipsychotic.
NCT01928446 — Li+ plus, lithium versus placebo for repeat suicide-related outcomes (NCT01928446) · a recorded source, not a stored snapshot
What that does for a person
Fewer episodes over years, no measured effect on repeated suicide attempts
In the largest randomised comparison, lithium delayed the next mood episode better than valproate over two years. In the largest randomised test of its suicide-prevention claim, it did not separate from placebo.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
BALANCE: hazard ratio 0.71 (95% CI 0.51 to 1.00, p=0.0472) for lithium against valproate for a new intervention for an emergent mood episode, in 330 patients over up to 24 months, open-label. Li+ plus: hazard ratio 1.10 (95% CI 0.77 to 1.55) for time to a repeated suicide-related event in 519 veterans, double-blind and placebo-controlled, stopped for futility.
NCT01928446 — Li+ plus, lithium versus placebo for repeat suicide-related outcomes (NCT01928446) · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
People with bipolar disorder, for acute mania and for long-term prevention. It is also used to augment antidepressants in resistant depression, which is not an approved indication in the United States.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “The safety and effectiveness of lithium has not been established in pediatric patients less than 7 years of age with bipolar I disorder.”
US prescribing information · d3284649-ed4c-4096-987b-4ac16b8278f2 · read 2026-08-30
On older people, the label states: “Clinical studies of lithium carbonate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.”
US prescribing information · d3284649-ed4c-4096-987b-4ac16b8278f2 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Lithium may cause harm when administered to a pregnant woman.”
US prescribing information · d3284649-ed4c-4096-987b-4ac16b8278f2 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Limited published data reports the presence of lithium carbonate in human milk with breast milk levels measured at 0.12 to 0.7 mEq or 40 to 45% of maternal plasma levels.”
US prescribing information · d3284649-ed4c-4096-987b-4ac16b8278f2 · read 2026-08-30
On people with reduced kidney function, the label states: “As lithium is eliminated primarily through the kidney, lithium renal clearance is decreased in patients with abnormal renal function, and the risk of lithium intoxication increases considerably in this setting.”
US prescribing information · d3284649-ed4c-4096-987b-4ac16b8278f2 · read 2026-08-30
Where the result stopped carrying
The Li+ plus suicide-prevention trial was stopped for futility after 519 randomisations
BALANCE's lithium-against-valproate result has an upper confidence limit of exactly 1.00, in an unblinded trial whose endpoint is a clinician's decision
No randomised trial has been able to attribute lithium's effect to any molecular mechanism, seventy-seven years after its first psychiatric use
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral immediate-release capsule or tablet, oral solution, and extended-release tablet
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
There is no injectable and no long-acting depot.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: Absorption is complete and clearance is entirely renal, in parallel with sodium handling, which is why the interaction list is dominated by non-steroidal anti-inflammatories, ACE inhibitors, angiotensin receptor blockers and thiazide diuretics rather than by other psychiatric drugs. Extended-release forms smooth the peak concentration but do not change the requirement for serum monitoring.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
The United States label carries a boxed warning for lithium toxicity, stating that toxicity is closely related to serum concentrations, can occur at doses close to therapeutic ones, and that facilities for prompt and accurate serum determinations should be available before treatment begins. Toxic concentrations begin at 1.5 mEq/L against a therapeutic range of 0.8 to 1.2 mEq/L, and some patients show toxic signs within the therapeutic range. There is no specific antidote for lithium poisoning. Named long-term risks are chronic kidney disease with structural changes, hypothyroidism and hyperthyroidism, hypercalcaemia and hyperparathyroidism, an encephalopathic syndrome when combined with an antipsychotic, and unmasking of Brugada syndrome. Risk of toxicity rises with febrile illness, dehydration, sodium depletion, impaired renal function and interacting drugs.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
NCT01928446 — Li+ plus, lithium versus placebo for repeat suicide-related outcomes (NCT01928446) · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral immediate-release capsule or tablet, oral solution, and extended-release tablet
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: Absorption is complete and clearance is entirely renal, in parallel with sodium handling, which is why the interaction list is dominated by non-steroidal anti-inflammatories, ACE inhibitors, angiotensin receptor blockers and thiazide diuretics rather than by other psychiatric drugs. Extended-release forms smooth the peak concentration but do not change the requirement for serum monitoring.
No source is stored against this line.
What is recorded as being sold
147 products list this as an active ingredient in the United States drug directory. 85 of them contain it and nothing else.
FDA National Drug Code directory · 39345-5104 · read 2026-08-29
They are sold as capsule, capsule, gelatin coated, gel, liquid, pellet and powder, taken oral, sublingual and topical.
FDA National Drug Code directory · 39345-5104 · read 2026-08-29
The regulator's established pharmacologic class for it is mood stabilizer [epc].
FDA National Drug Code directory · 39345-5104 · read 2026-08-29
118 published labels name it as an active ingredient. 56 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 05341147-789a-4844-9412-6a3044e5eb18 · read 2026-08-29
Those labels are classed as human otc drug and human prescription drug.
US prescribing information · 05341147-789a-4844-9412-6a3044e5eb18 · read 2026-08-29
2851 marketed supplement labels list this ingredient, classed as mineral and other combinations.
Those labels carry all other, nutrient and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
Lithium Carbonate is oral at 3 DOSAGE FORMS AND STRENGTHS Each 300 mg tablet for oral administration contains: lithium carbonate USP and is white to off-white, circular, biconvex, uncoated tablet debossed with “430” on one side and break line on ot…, recorded as fda label in effect 2023-10-02 in the United States.
US prescribing information · d3284649-ed4c-4096-987b-4ac16b8278f2 · read 2026-08-30
Recorded price in US: 0.08766–0.24015 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 25 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Lithium Carbonate studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That lithium prevents suicide — the one adequately powered randomised test of that claim was stopped for futility at a hazard ratio of 1.10
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That lithium works by inhibiting glycogen synthase kinase-3 or by depleting inositol — both are hypotheses and neither appears in the label
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That lithium is established as superior across bipolar disorder — the randomised head-to-head evidence is one open-label trial of 330 patients against one comparator
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a combination of lithium and valproate is better than lithium alone — BALANCE reports it could neither confirm nor refute that (hazard ratio 0.82, 95% CI 0.58 to 1.17)
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Lithium Carbonate are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
The suicide-prevention trial was stopped for futility
In plain words
Lithium's most repeated claim is that it prevents suicide. A randomised placebo-controlled trial in 519 veterans who had recently survived a suicide-related event was stopped early because it was not going to show a benefit.
What was measured
Hazard ratio for time to first repeated suicide-related event: 1.10 (95% CI 0.77 to 1.55), trial stopped for futility
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The Li+ plus trial, registered as NCT01928446 and run across 29 Department of Veterans Affairs medical centres, randomised veterans with bipolar disorder or major depression who had had an episode of suicidal behaviour or an admission to prevent suicide within six months. Participants received extended-release lithium carbonate or placebo added to usual care. The trial was stopped for futility after 519 randomisations, 255 to lithium and 264 to placebo. The primary outcome, time to the first repeated suicide-related event, gave a hazard ratio of 1.10 (95% CI 0.77 to 1.55). A total of 127 participants (24.5%) had a suicide-related outcome: 65 on lithium and 62 on placebo. One death occurred in the lithium group and three in the placebo group. Mean lithium concentrations at three months were 0.54 mEq/L in the bipolar group and 0.46 mEq/L in the depression group, which sit below the 0.8 to 1.2 mEq/L therapeutic range the label states, and that is a real limitation on how far the null result generalises. The authors' conclusion is that simply adding lithium to existing regimens is unlikely to be effective for preventing a broad range of suicide-related events in patients already being treated for mood disorders and substantial comorbidities.
Written into the record, not signed off as a reviewed claim
It beat valproate on relapse prevention over two years
In plain words
An open-label trial randomised 330 people with bipolar I disorder to lithium, valproate or both, and followed them for up to two years. Lithium alone did better than valproate alone on the number of people needing treatment for a new episode.
What was measured
Hazard ratio 0.71 (95% CI 0.51 to 1.00, p=0.0472) for lithium against valproate for a new intervention for an emergent mood episode over up to 24 months
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
BALANCE, registered as ISRCTN 55261332 and funded by the Stanley Medical Research Institute and Sanofi-Aventis, randomised 330 patients aged 16 and over at 41 sites in the United Kingdom, France, the United States and Italy, after a four-to-eight-week run-in on the combination. A primary outcome event — initiation of a new intervention for an emergent mood episode — occurred in 59 of 110 (54%) on combination therapy, 65 of 110 (59%) on lithium and 76 of 110 (69%) on valproate. Hazard ratios were 0.59 (95% CI 0.42 to 0.83, p=0.0023) for combination against valproate, 0.71 (95% CI 0.51 to 1.00, p=0.0472) for lithium against valproate, and 0.82 (95% CI 0.58 to 1.17, p=0.27) for combination against lithium. The trial was open-label: investigators and participants knew the allocation, and only the outcome-adjudicating trial management team was masked. The authors state the trial could neither reliably confirm nor refute a benefit of combination therapy over lithium alone.
Written into the record, not signed off as a reviewed claim
Seventy years in, the label still says the mechanism is unknown
In plain words
Section 12.1 of the United States prescribing information consists of one sentence: the mechanism of action of lithium as a mood stabilising agent is unknown.
What was measured
That lithium works by inhibiting glycogen synthase kinase-3 or by depleting inositol — both are research hypotheses and neither appears in the approved label
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
That single sentence is the entire mechanism section of the approved label, for a drug in continuous psychiatric use since 1949 and approved in the United States in 1970. The research literature has proposed inhibition of glycogen synthase kinase-3 beta, depletion of inositol through inhibition of inositol monophosphatase, effects on circadian genes and neuroprotective effects on grey matter volume. None of them has met the standard required to appear in the label as a mechanism. This is worth reading in both directions. It is a genuine and unusual admission of ignorance in a regulatory document. It is also a warning about every mechanistic account of a psychiatric drug: the mechanism sections of the other labels on this page are also hedged, and several of them say the mechanism "is unclear" and then offer a proposal. Lithium is the one that does not offer a proposal.
Source
United States prescribing information for lithium carbonate, section 12.1, via the openFDA drug label endpoint
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The toxic concentration starts at 1.5 mEq/L and the therapeutic range ends at 1.2
In plain words
The blood level that helps and the blood level that poisons are separated by three tenths of a unit. The label carries a boxed warning saying so, and adds that some people show toxic signs while still inside the therapeutic range.
What was measured
Serum lithium concentration: therapeutic 0.8 to 1.2 mEq/L, toxic at or above 1.5 mEq/L
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The boxed warning states that lithium toxicity is closely related to serum lithium concentrations and can occur at doses close to therapeutic concentrations, and that facilities for prompt and accurate serum lithium determinations should be available before starting treatment. Section 5.1 states that toxic concentrations are at or above 1.5 mEq/L against a therapeutic range of 0.8 to 1.2 mEq/L, and that some patients abnormally sensitive to lithium may show toxic signs at concentrations considered within the therapeutic range. It also records that lithium may take up to 24 hours to distribute into brain tissue, so acute toxicity may be delayed. Toxicity runs from fine tremor and unsteadiness through confusion, seizure, coma and death, with neurological sequelae that may persist after stopping and may be associated with cerebellar atrophy; cardiac manifestations include QT prolongation and myocarditis; renal manifestations include nephrogenic diabetes insipidus and renal failure. The label states that no specific antidote for lithium poisoning is known. Risk is raised by febrile illness, dehydration, volume depletion, sodium changes, impaired renal function, significant cardiovascular disease, and drugs that raise lithium concentrations or affect kidney function.
Source
United States prescribing information for lithium carbonate, Boxed Warning and sections 5.1 and 10, via the openFDA drug label endpoint
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Three endocrine and renal consequences, each with its own monitoring instruction
In plain words
Long-term lithium can damage the kidneys, disturb the thyroid in either direction, and raise calcium through the parathyroid glands. The label names all three and tells prescribers to monitor for each.
What was measured
Named long-term consequences with monitoring instructions: chronic kidney disease with structural changes, thyroid dysfunction in both directions, hypercalcaemia and hyperparathyroidism
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Warnings and Precautions summary lists lithium-induced chronic kidney disease, stated to be associated with structural changes in patients on chronic lithium therapy, with an instruction to monitor kidney function; hypothyroidism and hyperthyroidism, with an instruction to monitor thyroid function regularly; and hypercalcaemia and hyperparathyroidism, stated to be associated with long-term lithium use, with an instruction to monitor serum calcium. It separately lists an encephalopathic syndrome with increased risk in patients treated with lithium together with an antipsychotic, and directs routine monitoring for changes in cognitive function — which matters because combining lithium with an antipsychotic is one of the commonest regimens in bipolar disorder. These are not rare idiosyncratic reactions. They are the expected long-term cost of a drug that people take for decades, and each one is detected by a blood test that is cheap and frequently not ordered.
Source
United States prescribing information for lithium carbonate, sections 5.4, 5.5, 5.7 and 5.8, via the openFDA drug label endpoint
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The reputation as the gold standard outruns the randomised evidence behind it
In plain words
Lithium is described almost universally as the gold-standard mood stabiliser. The randomised evidence for that consists largely of one open-label two-year trial in 330 people, and the specific claim most often attached to it failed its own trial.
What was measured
That lithium is established as superior to the alternatives across bipolar disorder — the randomised head-to-head evidence is one open-label trial of 330 patients against a single comparator
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
BALANCE is the largest randomised comparison of lithium against an active alternative for relapse prevention in bipolar I disorder, and it enrolled 330 people, was open-label, and produced a hazard ratio against valproate of 0.71 with an upper confidence limit of exactly 1.00 and p=0.0472. That is a positive result at the margin of significance in an unblinded trial. The suicide-prevention claim, which is the one most often used to argue lithium is unique, comes from observational studies and meta-analyses of small trials, and the one adequately powered randomised test of it was stopped for futility with a hazard ratio of 1.10. None of this makes lithium a bad drug: it beat its comparator on a hard two-year endpoint, which most drugs on this page have never been asked to do. It does mean the gap between the strength of the reputation and the strength of the trial evidence is unusually wide, and that a reader should know the size and design of BALANCE before repeating the phrase.
Written into the record, not signed off as a reviewed claim
It can unmask a cardiac syndrome that causes sudden death
In plain words
Post-marketing reports link lithium to unmasking Brugada syndrome, an inherited electrical abnormality of the heart that carries a risk of sudden death. The label says lithium should be avoided in anyone who has it or is suspected of having it.
What was measured
Post-marketing reports of Brugada syndrome unmasking during lithium treatment
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label records post-marketing reports of a possible association between lithium treatment and the unmasking of Brugada syndrome, describes the syndrome as characterised by abnormal electrocardiographic findings and a risk of sudden death, and states that lithium should be avoided in patients with Brugada syndrome or suspected of having it. It recommends cardiology consultation where lithium is under consideration in someone suspected of having it or carrying risk factors — unexplained syncope, a family history of Brugada syndrome, or a family history of sudden unexplained death before age 45 — and in patients who develop unexplained syncope or palpitations on treatment. The practical significance is that the risk factors are questions a prescriber has to think to ask, since none of them appears in a routine psychiatric history.
Source
United States prescribing information for lithium carbonate, Warnings and Precautions (Unmasking of Brugada Syndrome), via the openFDA drug label endpoint
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
How many documents were read
54 documents were read for this substance.
RNAWiki source record
24 of them state the same halfLife, and they agree.
RNAWiki source record
24 of them state the same tMax, and they agree.
RNAWiki source record
24 of them state the same volumeOfDistribution, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
2BMD2GNA4V
RxNorm concept
197891
Checks this page had to pass
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Identity resolved
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No unresolved merge across substance families
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Every public sentence names a source
The opening statement carries the origin: Written into the record, not signed off.
✗ Not passed
Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
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No internal keys in reader text
enforced by the copy-contract test over the rendered page
✗ Not passed
Safety mode resolved
No register row and no identity class settled the question.
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Canonical metadata present
slug and display name present
What is missing or unclear◇Read from sources, not yet reviewed
How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
What the approval register records
36 approved applications cover products containing this substance. The earliest was NDA016834, approved 19700406 to PFIZER.
This order is fixed in code and does not count clicks or time on the page.
What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
An element with no known mechanism, no receptor and no patent, which beat valproate on preventing relapse in bipolar I disorder over two years (hazard ratio 0.71, 95% CI 0.51 to 1.00) and then failed its own suicide-prevention trial, stopped for futility after 519 veterans with a hazard ratio of 1.10 (95% CI 0.77 to 1.55), while carrying a boxed warning because the toxic blood concentration begins at 1.5 mEq/L and the therapeutic range ends at 1.2.
Recorded evidence blocks (9)
Q1
On the Lithium Carbonate label: indicated for what?
"Lithium is a mood-stabilizing agent indicated as monotherapy for the treatment of bipolar I disorder: • Treatment of acute manic and mixed episodes in patients 7 years and older [see Clinical Studies ( 14 )] • Maintenance treatment in patients 7 years and older [see Clinical Studies ( 14 )] Lithium is a…": indications and usage on Lithium Carbonate's label. DailyMed label · 582697c1-063f-366f-e063-6294a90a8d1b · 2026-08-03
Q2
94 registered trials of Lithium Carbonate — at which phases?
Registered studies posting no result
63 of 94
94 registered studies of Lithium Carbonate: 29 phase2, 24 phase4, 23 phase3, 17 phase1, 7 na, 4 na or unstated, 1 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
18 to 36 hours; The elimination half-life of lithium is approximately 18 to 36 hours.
tmaxpharmacokinetics
0.25 to 3 hours; Peak serum concentrations (T max ) occur 0.25 to 3 hours after oral administration of immediate release preparations and 2 to 6 hours after sustained-release preparations.
metabolismpharmacokinetics
Metabolism: Lithium is not metabolized.
recorded 2026-08-03 · last checked 2026-09-04
Q6
Which 35 trials of Lithium Carbonate posted no result?
Posted no result
35 of 35 completed trials
Registrations
NCT00000369, NCT00177567, NCT00870311, NCT00485680, NCT00114439 and NCT00641927, and 29 more
Completion dates
oldest 2002-12; newest 2024-08-26
Show the evidence
Trial
NCT00000369
2002-12
NCT00177567
2004-01
NCT00870311
2004-04
NCT00485680
2005-06
NCT00114439
2006-09
NCT00641927
2006-10
14 further recorded trials
NCT00202306
2006-12
NCT00221975
2007-12
NCT00442039
2009-09
NCT00431171
2010-01
NCT00683943
2010-02-25
NCT01977300
2011-08
NCT00627887
2012-05
NCT00276965
2012-07
NCT03965247
2012-09-04
NCT00998634
2012-11
NCT01096082
2013-01
NCT01166425
2013-04
NCT00548964
2013-07
NCT01354483
2013-12
Q7
At the median, Lithium Carbonate's trials enrolled 51 people — anything larger?
Median enrolment
51
Largest enrolment
1037352
Registered trials counted
93
Q8
What do 4443 spontaneous reports say about Lithium Carbonate — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Lithium Carbonate appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 4443 reaction mentions were counted: toxicity to various agents 1253; tremor 625; drug interaction 513; confusional state 408. FAERS via Open Targets · CHEMBL1200826 · 2026-06-24
Show the evidence
toxicity to various agents
1253
tremor
625
drug interaction
513
confusional state
408
neuroleptic malignant syndrome
311
weight increased
295
4 more recorded rows
suicide attempt
274
acute kidney injury
270
somnolence
255
therapeutic agent toxicity
239
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Lithium Carbonate's label not list?
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 6 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.