Mood Stabilizer Adverse Events · Section 2 · Chapter 5 · Lithium
Lithium and Declining Kidney Function: CKD, Proteinuria and When to Reconsider Treatment
Long-term lithium is associated with a slow fall in kidney function in some patients. Most never reach severe kidney disease; a minority do, and for them the window in which stopping lithium helps may close before anyone decides. This chapter is about reading the trend, acting on it, and making the continue-or-stop decision on purpose rather than by default.
The 30-second version
- What lithium does to kidney function over time. The main long-term lesion is a chronic tubulointerstitial nephropathy. Lithium is associated with more moderate chronic kidney disease than comparator mood stabilizers; severe kidney disease is uncommon and concentrated in older patients with long exposure.
- Reading the trend. Measure eGFR before lithium and regularly during it: recommendations range from every three to six months to once or twice a year, more often in older patients and after any decline or toxicity episode. Act on a sustained fall across several results, not on a single value.
- Who is at risk. Long exposure, older age, higher serum levels, previous toxicity episodes, and other kidney risks such as diabetes, high blood pressure and diuretics. Most of these you can see coming.
- Slowing the decline. Keep the level as low as keeps the patient well, prevent toxicity episodes, and manage the other kidney risks. When kidney function is already reduced, the label asks for lower doses, slow titration and frequent levels.
- Continue or stop. There is no single eGFR at which lithium must stop, and the evidence on how much stopping helps at low eGFR is split. Make the decision with the patient and a nephrologist while the eGFR is still well above 30, when the evidence is clearest, weighing a sustained decline against the psychiatric cost of losing lithium.
- Proteinuria and nephrotic syndrome. Heavy proteinuria is not the typical picture of lithium nephropathy. Refer it. The label does report nephrotic syndrome on lithium, with remission when lithium was stopped.
At the bedside: a falling eGFR in a patient on lithium
About 2 min to read · the detailed chapter follows below
Do now
- Plot every eGFR you can find, with dates. Decide on the trend, not on the latest number.
- Rule out a reversible cause: an episode of toxicity, dehydration, an NSAID, a new ACE inhibitor, ARB or diuretic.
- Check a urine protein test, blood pressure, glucose, calcium and a 12-hour lithium trough.
- Review whether the current lithium level is needed. Lower is kinder to the kidney.
- If the fall is sustained, involve nephrology and make the continue-or-stop decision with the patient, in writing.
Do not
- Stop lithium abruptly because of one low eGFR.
- Wait for the eGFR to fall below 30 before discussing the future of lithium.
- Treat an eGFR "within the normal range" as reassurance if it is falling.
- Assume heavy proteinuria is lithium's doing without further work-up.
- Leave the decision to whoever sees the next result.
Five questions to ask
- What is the trend over the last few years? A single value tells you little; three or more in a row tell you the direction.
- Was there a toxicity episode, dehydration or a new interacting drug? Each can cause a fall that may partly recover.
- What other kidney risks does the patient have? Age, diabetes, high blood pressure, diuretics, NSAIDs.
- How well is lithium working, and what happened when it was stopped before? This is the other side of the scale.
- Is there protein or blood in the urine? Heavy proteinuria needs its own work-up.
Same day if any of
- A sudden fall in eGFR, or a rising creatinine with a raised lithium level
- Any sign of lithium toxicity: use Chapter 1's full toxicity triage
- Vomiting, diarrhoea or poor fluid intake with a falling eGFR
Re-evaluate within weeks if any of
- A sustained fall across three or more results, whatever the absolute value
- eGFR below 60 for the first time
- Protein or blood in the urine
- eGFR approaching 30–40: the continue-or-stop decision is due now
Routine, with a plan
Stable eGFR, no proteinuria: keep monitoring, keep the level no higher than needed, and manage the other kidney risks.
Prescriber-side triage for a falling eGFR on lithium. Our synthesis of the US label, a 2026 expert review, a nephrology review and a psychiatry editorial on eGFR monitoring, not a validated instrument [1][3][4][9].
Why one eGFR misleads
- A single result can be low after dehydration, a toxicity episode or a new drug, and partly recover.
- A result within the normal range can hide a steady fall.
- The decision point comes before the lowest numbers, not at them.
- eGFR falls with age anyway; the question is whether lithium is adding to it.
Tell the nephrologist
- Years on lithium, and the usual trough level
- eGFR and creatinine results over time, with dates
- Any toxicity episodes, and polyuria
- Other kidney risks and nephrotoxic drugs
- How well lithium has worked, and the psychiatric risk of stopping
Look up an eGFR range
Tap a range for what it means and what to do. The trend matters at every level.
Preserved
Re-evaluate
Decide now, or the label's boundary
eGFR 60 or above
Watch the trendMonitor at least yearly. Watch the trend: a steady fall matters even here.
What it means
- A result within the normal range can hide a steady fall
- Progressive or sudden changes, even within the normal range, call for re-evaluation [1][2]
What to do
- The UK NICE kidney guideline sets a floor of at least once a year for anyone taking lithium [15]
- Keep the level no higher than needed, and manage the other kidney risks
eGFR 30–59
Re-evaluateRe-evaluate: repeat tests, urine protein, lower the level, manage other risks, involve nephrology if falling.
What it means
- eGFR below 60 for the first time: re-evaluate within weeks
- A strict eGFR cut-off for stopping lithium is difficult to set, because many older adults have an eGFR below 60 [11]
What to do
- Repeat eGFR with other blood tests and urinalysis every three months once eGFR is in the 30–59 range [9]
- Check a urine protein test, blood pressure, glucose, calcium and a 12-hour lithium trough
- If the fall is sustained, involve nephrology and make the continue-or-stop decision with the patient, in writing
Approaching 30–40
Decide nowDecide now whether to continue. Evidence on recovery after stopping is weaker and contested below here.
What it means
- The 2026 expert review concludes that once eGFR falls below 30–40 mL/min, improvement after withdrawal is less likely [3]
- The evidence on how much stopping helps at low eGFR is split
- A low eGFR is not by itself a reason to assume stopping is pointless
What to do
- The continue-or-stop decision is due now
- Make the decision with the patient and a nephrologist while the eGFR is still well above 30
- Raising it does not mean stopping
- Record the decision, the reasons and the patient's view in the notes
Below 30
The label's boundaryThe label does not recommend lithium in severe kidney impairment, a creatinine clearance below 30 mL/min [1][2].
What the sources say
- In a Swedish series of lithium-treated patients with at least one eGFR below 30, about half had a transient fall followed by improvement [14]
- For patients who reached stage 4 disease, the authors of a 2025 Swedish study suggest keeping lithium in most cases at that stage [14]; that view sits against the label [1][2]
What to do
- Repeat a single low result once the cause has passed before drawing conclusions
- At that stage the decision belongs jointly to the patient, the psychiatrist and the nephrologist
All four ranges on one page (figure)
Figure 1. What each eGFR range means for a patient on lithium. Our summary of the US label, a 2026 expert review, a nephrology review and a psychiatry editorial [1][3][4][9]. The boundaries are guides for when to act, not cut-offs that decide for you. The trend matters at every level.
What lithium does to kidney function over time
The main long-term lesion is a chronic tubulointerstitial nephropathy. Lithium is associated with more moderate chronic kidney disease than comparator mood stabilizers; severe kidney disease is uncommon and concentrated in older patients with long exposure.
The label names the lesion. The predominant chronic kidney disease associated with long-term lithium is a chronic tubulointerstitial nephropathy, with biopsy findings that include tubular atrophy, interstitial fibrosis, sclerotic glomeruli and nephron atrophy with cyst formation. It can present with worsening kidney function, with nephrogenic diabetes insipidus, or with proteinuria [1][2]. The polyuria side of that picture is the subject of Chapter 4.
The detail: what the large cohort studies show
Large observational studies agree on the direction and differ on the size. In UK primary care records, lithium was associated with more chronic kidney disease of stage 3 or worse than valproate, but the authors could not exclude that closer monitoring of lithium patients inflated the difference, and it was unclear whether severe kidney disease was increased [7]. A second UK primary-care cohort found an increased risk of renal failure with lithium, with the absolute risk much higher in patients aged 50 or over [6]. A 2025 Hong Kong cohort found a modestly increased risk of stage 3 or worse disease with lithium, higher with higher serum levels, but no difference in stage 4 or worse disease or end-stage kidney disease [8].
Severe disease is the tail, not the body, of the distribution. A Swedish laboratory study following lithium-treated patients for more than 35 years found that severe chronic kidney disease (eGFR below 30) was uncommon overall, with negligible ten-year risk in patients starting lithium before 55, and most cases occurring after 70. Long exposure and a higher creatinine before lithium started were strong risk factors. The authors concluded that the risk does not justify withholding lithium from patients who might benefit, particularly younger ones [5].
Reading the trend
Measure eGFR before lithium and regularly during it: recommendations range from every three to six months to once or twice a year, more often in older patients and after any decline or toxicity episode. Act on a sustained fall across several results, not on a single value.
The practical skill is looking at the series. A psychiatry editorial that set out how to use eGFR in lithium monitoring suggested investigating a progressive fall across three or more serial tests, and repeating eGFR with other blood tests and urinalysis every three months once eGFR is in the 30–59 range [9]. The expert review makes the same point in different words: decisions should be individualised and based on the trajectory rather than reflexive [3].
Two traps
Two traps are worth naming. A single low result after a toxicity episode, dehydration or a new interacting drug may partly recover, so repeat it once the cause has passed before drawing conclusions. In a Swedish series of lithium-treated patients with at least one eGFR below 30, about half had a transient fall followed by improvement [14]. And eGFR declines with age in everyone; the question is whether the rate in this patient is steeper than age alone would explain, which is exactly what a nephrologist can help judge. The same Swedish authors warn against "creeping creatinine", a steady rise over years, and suggest a lower threshold for contacting a nephrologist in younger patients [14].
The detail: monitoring schedules and when to refer
The label asks for kidney function to be assessed before and during treatment, and says that progressive or sudden changes, even within the normal range, call for re-evaluation [1][2]. A 2026 expert review recommends creatinine and eGFR, with urea, sodium, potassium and calcium, once or twice a year, and more often in older patients, in those with a reduced baseline eGFR or a rapid decline, in those with relevant medical illness, and after any episode of lithium intoxication [3]. The CANMAT/ISBD bipolar guideline asks for renal function at six months and at least annually thereafter in maintenance treatment, and for creatinine, and ideally eGFR, at least every three to six months in the older adults in whom it describes a higher risk of chronic kidney disease [11]; the UK NICE kidney guideline sets a floor of at least once a year for anyone taking lithium [15].
For when to involve a nephrologist, the current UK NICE kidney guideline gives criteria that apply to any adult with chronic kidney disease, including a sustained decrease in eGFR of 25% or more with a change in eGFR category within 12 months, a sustained decrease of 15 mL/min or more per year, a five-year risk of needing kidney replacement therapy greater than 5% on the Kidney Failure Risk Equation, and significant albuminuria [15]. The same guideline lists lithium among the medicines for which eGFR should be monitored at least annually [15]. CANMAT/ISBD adds a point specific to lithium: a strict eGFR cut-off for stopping it is difficult to set, because many older adults have an eGFR below 60 [11].
Who is at risk
Long exposure, older age, higher serum levels, previous toxicity episodes, and other kidney risks such as diabetes, high blood pressure and diuretics. Most of these you can see coming.
| Risk factor | What the sources say | What you can do |
|---|---|---|
| Duration of treatment | The factor most consistently implicated [4]; long exposure strongly associated with severe disease [5] | Nothing directly, which is why the other factors matter more as the years pass |
| Older age | Absolute risk much higher from age 50 [6]; most severe cases after 70 [5] | Monitor more often; review the target level as the patient ages |
| Higher serum levels | Higher levels associated with more stage 3 disease [8]; an expert review notes that even modest levels may be too high for some patients [3] | Use the lowest level that keeps the patient well |
| Previous toxicity episodes | Listed among the risk factors for decline [4] | Prevent the next one: sick-day rules and interaction checks (Chapter 2) |
| Diabetes, high blood pressure, heart disease, diuretics | Diabetes and diuretic use associated with renal failure in lithium users [6]; hypertension and diabetes listed as risk factors [4]; cardiovascular comorbidity described as a strong risk factor [14] | Manage them actively; the Swedish authors call this mandatory [5] |
| Higher creatinine before lithium started | A strong predictor of severe disease [5] | A reason for closer monitoring from the start |
Slowing the decline
Keep the level as low as keeps the patient well, prevent toxicity episodes, and manage the other kidney risks. When kidney function is already reduced, the label asks for lower doses, slow titration and frequent levels.
Most of what slows the decline is ordinary lithium care done consistently. Three things carry most of the weight.
- The lowest level that worksHigher serum levels are associated with more chronic kidney disease [8], and an expert review cautions that even modest levels may be excessive for some patients [3]. Review the target with the patient's history of relapse in front of you, not by default.
- No more toxicity episodesPrevious toxicity is a risk factor for decline [4]. Sick-day rules, interaction checks and a standard letter to other prescribers (Chapter 2) are kidney protection as much as toxicity prevention.
- Blood pressure, glucose, drugsDiabetes, high blood pressure and diuretics add to the risk [4][6]. Avoid regular NSAIDs, and plan a level whenever a drug that affects lithium clearance is started.
Once kidney function is reduced, the label's dosing advice applies. It asks that patients with mild to moderately impaired kidney function start on lower doses than usual and be titrated slowly with frequent levels and monitoring for toxicity, and notes that the risk of lithium intoxication increases considerably when kidney function is abnormal [1][2]. That advice is written for starting lithium, but the logic holds for a patient whose function has fallen while on it: less clearance means the same dose produces a higher level.
Continue or stop
There is no single eGFR at which lithium must stop, and the evidence on how much stopping helps at low eGFR is split. Make the decision with the patient and a nephrologist while the eGFR is still well above 30, when the evidence is clearest, weighing a sustained decline against the psychiatric cost of losing lithium.
The label gives one firm boundary: it does not recommend lithium in severe kidney impairment, a creatinine clearance below 30 mL/min [1][2]. Above that, the decision is a judgement, and the evidence gives it a time element.
The detail: the evidence on stopping, both sides
Whether stopping lithium helps, and how late it can still help, is genuinely contested, and a prescriber should know both sides.
On one side, several studies found that patients who stop with better-preserved kidney function tend to stabilise or improve, while those with more damage often continue to decline. A 2023 review summarising this literature describes exactly that pattern, citing a 2022 study in which the patients whose function kept falling after stopping had a lower eGFR at the time than those who improved [12]. The 2026 expert review concludes that once eGFR falls below 30–40 mL/min, improvement after withdrawal is less likely [3], and a nephrology review warns that lithium nephropathy may continue to progress despite stopping [4].
On the other side, a 2025 Swedish mirror-image study compared kidney function in the five years before and after lithium was stopped in 168 patients who had taken it for at least four and a half years [10]. After stopping, the average yearly decline almost levelled off, and the effect lasted through the five years of follow-up. It was larger in patients whose kidney function was lower when lithium stopped: the yearly slope improved in nine of the ten patients whose eGFR was below 30 at that point. In patients who restarted lithium, the decline returned to its earlier rate, which the authors take as evidence that lithium itself was driving it [10]. The study was retrospective and from a single region, and its authors acknowledge possible selection bias. They also stress that any kidney benefit has to be weighed against the risk of relapse and suicide, and call for a patient-centred rather than a kidney-centred decision [10]. The CANMAT/ISBD guideline notes that a strict eGFR cut-off for discontinuation is difficult to set [11].
A third result is often quoted as the opposite. A 2026 Dutch prospective cohort followed 196 long-term lithium users for a median of almost nine years [13]. Of the patients who stopped lithium, 33 had follow-up afterwards. Their yearly decline was numerically lower after stopping, but the difference was not statistically significant, whether or not kidney function was the reason for stopping. The authors suggest this may reflect the small numbers and short follow-up [13]. The same study found that most long-term users lost kidney function faster than the general population, and that higher lithium levels and longer treatment were associated with faster decline [13].
Read closely, the Dutch and Swedish findings are less opposed than they first appear. The Dutch study had few patients who stopped, most with well-preserved kidney function, and its numbers moved in the same direction as the Swedish result. The Swedish benefit was largest in patients with low kidney function, which is exactly where the review and the expert review cited above expect stopping to help least. That disagreement, about patients with advanced decline, is the one that remains unresolved.
A 2025 Swedish study of lithium-treated patients who had already developed severe kidney impairment adds another perspective. Its authors note that stopping lithium does not invariably slow progression and that whether a "point of no return" exists is still a matter of discussion. Among their patients who reached stage 4 disease, survival did not differ between those who stopped lithium and those who continued, a finding they caution may reflect selection bias. Taking this with a Danish study in which continuing lithium after a diagnosis of kidney disease was not associated with more dialysis, and with the risk of relapse on stopping, they suggest keeping lithium in most cases at that stage [14]. That view sits against the label, which does not recommend lithium below a creatinine clearance of 30 mL/min [1][2]. At that stage the decision belongs jointly to the patient, the psychiatrist and the nephrologist.
What the sides agree on is enough to act on. The decision is best made early, when stopping is most predictable, and a low eGFR is not by itself a reason to assume stopping is pointless. Neither side supports waiting until the eGFR reaches the label's boundary before asking the question.
The time to raise the question is when a sustained decline is first recognised, not when the eGFR reaches the label's boundary. Raising it does not mean stopping. For many patients the answer will be to continue with a lower level, closer monitoring and active management of the other risks. The expert review is clear that lithium remains an invaluable treatment whose benefits often outweigh the risks when it is managed well [3].
| Weighs toward continuing | Weighs toward stopping or switching |
|---|---|
| A strong response to lithium, with serious relapses before it or when it was stopped | A sustained, steep decline despite a lower level and managed risk factors |
| A slow decline, or a fall explained by a reversible event | eGFR approaching the range where recovery after stopping becomes less likely |
| A stable eGFR at a lower level after adjustment | A partial response to lithium, with effective alternatives available |
| No acceptable alternative that has worked for this patient | Repeated toxicity episodes despite good care |
If the decision is to stop
Stopping is a psychiatric intervention with its own risks. Taper rather than stop abruptly, have a replacement strategy agreed before the taper begins, increase the frequency of psychiatric review during the change, and keep monitoring kidney function afterwards, because decline may continue for a time. The taper itself is the subject of Chapter 20 (releasing later). Record the decision, the reasons and the patient's view in the notes.
Proteinuria and nephrotic syndrome
Heavy proteinuria is not the typical picture of lithium nephropathy. Refer it. The label does report nephrotic syndrome on lithium, with remission when lithium was stopped.
The usual lithium lesion is tubulointerstitial, and the urine is often unremarkable: an expert review describes proteinuria, microscopic haematuria and leukocyturia as possible but inconsistent findings [3], and a nephrology review notes that heavy proteinuria is not a typical finding of lithium nephropathy [4]. The label does note that the tubulointerstitial lesion can present with nephrotic-range proteinuria [1], so heavy proteinuria does not exclude lithium; it calls for its own work-up rather than being attributed to lithium by default.
There is one exception worth knowing. The label reports post-marketing cases consistent with nephrotic syndrome, with or without the tubulointerstitial lesion, with biopsies showing minimal change disease or focal segmental glomerulosclerosis, and says that stopping lithium has resulted in remission [1][2]. New heavy proteinuria or oedema in a patient on lithium goes to nephrology promptly, with lithium named in the referral.
Clinical pearls
- Read eGFR as a series.The label's warning is about change, even within the normal range.
- Repeat a single low result after a toxicity episode, dehydration or a new drug before drawing conclusions.
- Severe kidney disease on lithium is uncommon and concentrated in older patients with long exposure.Moderate decline is common.
- Higher levels are associated with more kidney disease.Use the lowest level that keeps the patient well.
- Every toxicity episode prevented is kidney protection.
- Studies disagree on how much stopping helps once eGFR is low.Decide early, when the evidence is clearest, and do not assume stopping is pointless later.
- A falling eGFR is a reason to decide, not a reason to stop.Many patients continue safely with changes.
- Heavy proteinuria is not the typical lithium picture.Refer it, and name lithium in the referral.
- Write the decision down, with the reasons and the patient's view.
Patient script & EMR note
Counselling script: to the patient
"I want to talk about your kidney tests, because they've been drifting down over the last few years. That's something lithium can do in some people who've taken it for a long time. It isn't an emergency, and it doesn't mean you have to stop lithium. But it does mean we should make a plan now, rather than wait.
Here's what I'd suggest. We'll recheck your kidney tests and your urine, make sure your blood pressure is well controlled, and bring your lithium level down a little, to the lowest level that has kept you well. I'd also like a kidney specialist to look at your results with us.
The reason for doing this now is that, if your kidneys keep declining, the evidence about stopping lithium is clearest when the decision is made earlier. So we'll keep an eye on the trend and decide together, with plenty of time.
I haven't forgotten how well you've been on lithium, or what things were like before. That's part of the decision too, and we won't lose sight of it."
EMR note: copy, paste and edit
LITHIUM – KIDNEY FUNCTION REVIEW
Years on lithium: [ ] Usual 12-h trough: [value] mEq/L
eGFR series (date: value):
[ ] [ ] [ ] [ ] [ ]
Trend: [stable / slow decline / sustained decline / sudden fall]
Reversible causes considered: toxicity episode [ ], dehydration [ ],
NSAID [ ], ACE inhibitor / ARB [ ], diuretic [ ], other [ ]
Urine protein test: [ ] Blood pressure: [ ] Glucose: [ ]
Calcium: [ ] Polyuria: [Y/N]
Psychiatric side of the decision:
Response to lithium: [ ]
Relapse history before / off lithium: [ ]
Alternatives tried: [ ]
Assessment: [ ]
Plan:
[ ] Lithium target reviewed: [unchanged / lowered to ]
[ ] Other kidney risks addressed: [ ]
[ ] Monitoring: eGFR every [ ] months
[ ] Nephrology referral: [sent date / not needed because ]
[ ] Continue-or-stop decision: [continue / plan to switch /
review at ] – discussed with patient, their view: [ ]
[ ] What would change the decision: [ ]
Clinician: [ ] Date: [ ]
Case: Monday, 2:10 pm
A 66-year-old woman with bipolar I disorder has taken lithium for 22 years. Before lithium she had four admissions in six years; since, she has had none. Her troughs sit around 0.7 mEq/L. She has treated high blood pressure.
Her primary care physician writes: her eGFR is 46, she now has "CKD stage 3," and should lithium be stopped? Looking back through the record, her eGFR was 72 six years ago, 58 four years ago and 51 two years ago. Nobody has commented on any of them.
She has read about lithium and kidneys online and is frightened. She also remembers, clearly, what her life was like before lithium.
By the end of this chapter you should be able to say what the trend means, what to do this month, and how to make the continue-or-stop decision with her rather than for her.
Case resolution
Her eGFR has fallen steadily from 72 to 46 over six years. That is a sustained decline across four results, and the label's advice to re-evaluate applied several results ago. Nothing about it calls for stopping lithium today; everything about it calls for a decision this month.
The clinician repeats the eGFR with a urine protein test, checks her blood pressure control and her medication list for NSAIDs and diuretics, and reviews her level. Her urine shows no significant protein. Her blood pressure is above target; her primary care physician adjusts her treatment, avoiding a diuretic. Her lithium target is lowered, with a level booked.
She is referred to nephrology with the full series of results, her years on lithium, and her psychiatric history. The clinician tells her plainly that the goal is to keep lithium if it can be kept safely, and to decide together while her kidney function is still well preserved, when the evidence about stopping is clearest.
The plan is written down: eGFR every three months, a review of the decision at each result, and a clear statement of what would change it.
Why slow harms get missed
Lithium's effect on kidney function is slow, and slow harms are the ones clinical systems handle worst. Each eGFR is looked at by a different person, each is a little lower than the last, and each is still "acceptable." The label's warning is written for exactly this pattern: a progressive change, even within the normal range, is a reason to re-evaluate. The decision that matters is usually made years before the numbers look alarming, or it is not made at all.
References (15)
- Lithium carbonate [US prescribing information]. Dosage and Administration (renal impairment), Warnings and Precautions (5.4 lithium-induced chronic kidney disease) and Use in Specific Populations (8.6 renal impairment). Hikma Pharmaceuticals USA Inc.; revised November 2022. DailyMed setid 7dc9c6d2-6d9a-49e4-a8ab-437b0ed5f84e. Source type: US structured product label.
- Lithium carbonate [US prescribing information]. Dosage and Administration (renal impairment) and Warnings and Precautions (5.4). Sun Pharmaceutical Industries, Inc.; revised October 2023. DailyMed setid d3284649-ed4c-4096-987b-4ac16b8278f2. Source type: US structured product label from a different manufacturer.
- Strandhave C, Hansen HAS, Alda M, Bauer M, Berk M, et al. Lithium effects on renal functioning: an expert opinion and management algorithm. Int J Bipolar Disord. 2026;14:22. doi:10.1186/s40345-026-00423-z. Source type: international expert opinion.
- Davis J, Desmond M, Berk M. Lithium and nephrotoxicity: a literature review of approaches to clinical management and risk stratification. BMC Nephrol. 2018;19:305. doi:10.1186/s12882-018-1101-4. Source type: peer-reviewed narrative review.
- Golic M, Aiff H, Attman PO, Ramsauer B, Schön S, Steingrimsson S, Svedlund J. Lifetime risk of severe kidney disease in lithium-treated patients: a retrospective study. Int J Bipolar Disord. 2023;11:39. doi:10.1186/s40345-023-00319-2. Source type: retrospective cohort study (laboratory database).
- Close H, Reilly J, Mason JM, Kripalani M, Wilson D, Main J, Hungin APS. Renal failure in lithium-treated bipolar disorder: a retrospective cohort study. PLoS One. 2014;9:e90169. doi:10.1371/journal.pone.0090169. Source type: retrospective cohort study (UK primary care database).
- Hayes JF, Marston L, Walters K, Geddes JR, King M, Osborn DPJ. Adverse renal, endocrine, hepatic, and metabolic events during maintenance mood stabilizer treatment for bipolar disorder: a population-based cohort study. PLoS Med. 2016;13(8):e1002058. doi:10.1371/journal.pmed.1002058. Source type: population-based cohort study.
- Chan JKN, Solmi M, Correll CU, et al. Lithium for bipolar disorder and risk of thyroid dysfunction and chronic kidney disease. JAMA Netw Open. 2025;8(2):e2458608. doi:10.1001/jamanetworkopen.2024.58608. Source type: population-based retrospective cohort study.
- Morriss R, Benjamin B. Lithium and eGFR: a new routinely available tool for the prevention of chronic kidney disease. Br J Psychiatry. 2008;193:93–95. doi:10.1192/bjp.bp.108.051268. Source type: editorial.
- Fransson F, Werneke U, Öhlund L, Jonsson PA, Ott M. Kidney function decline improves after lithium discontinuation. J Intern Med. 2025;297:289–299. doi:10.1111/joim.20054. Source type: retrospective mirror-image cohort study.
- Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Bond DJ, Frey BN, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20:97–170. doi:10.1111/bdi.12609. Section 8.3.3, p144. Source type: clinical practice guideline.
- Gitlin M, Bauer M. Key questions on the long term renal effects of lithium: a review of pertinent data. Int J Bipolar Disord. 2023;11:35. doi:10.1186/s40345-023-00316-5. Source type: peer-reviewed narrative review.
- van der Aa MJ, Zittema D, Doornebal J, Hartong EGTM, Bisseling EM, Dammers J, et al. A significant decline of glomerular filtration rate in the majority of long-term lithium users: results of a Dutch prospective 10-year cohort study. Bipolar Disord. 2026;28:e70082. doi:10.1111/bdi.70082. Source type: prospective cohort study.
- Aiff H, Attman PO, Golic M, Ramsauer B, Schön S, Steingrimsson S, Svedlund J. Prospects for lithium treated patients with severe renal impairment. Int J Bipolar Disord. 2025;13:5. doi:10.1186/s40345-025-00372-z. Source type: retrospective register study with chart review.
- National Institute for Health and Care Excellence. Chronic kidney disease: assessment and management (NG203). Recommendations 1.1.20 and 1.5.5. London: NICE; 2021 (updated). Source type: national clinical guideline.
Last reviewed October 2026. Part of the Psychiatry Education Forum Academy, Managing Mood Stabilizer Adverse Events · Section 2 · Chapter 5.
Managing Mood Stabilizer Adverse Events
The rest of the course applies the same rapid-decision format to the serious adverse effects of lithium, valproate, lamotrigine, carbamazepine and oxcarbazepine: thyroid and calcium effects on lithium, hyperammonaemia on valproate, the rash that has to stop lamotrigine, stopping mood stabilizers safely, and more.
This chapter is educational material for licensed prescribers and prescribers in training. It is not a substitute for clinical judgement, nephrology advice, local protocols or the current prescribing information. Decisions about continuing or stopping lithium should be made with the patient and, where kidney function is declining, with a nephrologist. Psychiatry Education Forum Academy is not a CME provider and this chapter does not carry CME credit.
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