From the Guidelines
Lithium therapy should be discontinued when a patient's glomerular filtration rate (GFR) falls below 30 mL/min/1.73m² due to the increased risk of lithium toxicity. At this level of kidney function, the risk of lithium toxicity significantly increases due to reduced renal clearance of the medication 1. For patients with a GFR between 30-60 mL/min/1.73m², lithium can typically be continued but requires more frequent monitoring of lithium levels and kidney function, with potential dose reductions.
Key Considerations
- The risk-benefit of lithium therapy in patients with impaired renal function must be carefully weighed, considering the potential for renal tubular dysfunction and nephrotoxicity even at therapeutic levels 1.
- Patients on lithium therapy should be monitored regularly, with assessments of GFR, electrolytes, and lithium levels every 6 months or more frequently if the dose changes or the patient is acutely unwell 1.
- Concomitant use of NSAIDs should be avoided, and patients should maintain hydration during intercurrent illness to minimize the risk of lithium toxicity 1.
- When discontinuing lithium in patients with declining renal function, it should be done gradually under close medical supervision to prevent withdrawal symptoms and mood destabilization.
- Alternative mood stabilizers such as valproate, lamotrigine, or certain atypical antipsychotics may need to be considered as replacement therapy.
Clinical Decision Making
The decision to discontinue lithium therapy due to impaired renal function should be based on the most recent and highest quality evidence available, taking into account the individual patient's risk factors and clinical circumstances. In the absence of more recent guidelines, the recommendation to stop lithium at GFR <30 mL/min/1.73m² remains a prudent approach, given the medication's narrow therapeutic index and the fact that lithium is almost entirely eliminated by the kidneys, making patients with significant renal impairment particularly vulnerable to toxicity even at standard therapeutic doses.
From the Research
Discontinuation of Lithium Therapy due to Impaired Renal Function
The decision to discontinue lithium therapy due to impaired renal function is a complex one, and the evidence suggests that it should be based on individual patient factors, including the severity of renal impairment and the duration of lithium treatment.
- A study published in 2010 2 found that lithium treatment is associated with a modest decline in renal function, and that the percentage of patients with an eGFR < 60 ml/min/1.73 m2 was significantly higher in lithium-treated patients compared to controls.
- Another study published in 2019 3 found that both renal concentrating ability and eGFR are inversely associated with the duration of lithium therapy, and that 19% of patients had an eGFR ≤ 60 ml/min/1.73 m2.
- A study published in 2025 4 found that a measurement of eGFR < 30 ml/min/1.73 m2 reflects a significant loss of renal function, and that patient survival can be counted in several years after debut of renal insufficiency with appropriate care, including renal replacement therapy.
- A study published in 2025 5 found that stopping lithium slowed down mean eGFR decline, and that this effect was more pronounced in participants with lower eGFR at the time of lithium discontinuation.
- A study published in 2013 6 found that the duration of lithium treatment is a risk factor for glomerular failure, and that eGFR was estimated to decrease by 0.64 ml/min for each year of lithium treatment.
Glomerular Filtration Rate (GFR) Threshold for Discontinuation
The evidence suggests that a GFR threshold of < 30 ml/min/1.73 m2 may be a reasonable indicator for discontinuing lithium therapy due to impaired renal function 4, 5. However, this decision should be individualized and based on a comprehensive assessment of the patient's overall health and treatment goals.
- Patients with a GFR < 30 ml/min/1.73 m2 may be at increased risk of lithium toxicity and may require more frequent monitoring of renal function and lithium levels 4.
- Discontinuation of lithium therapy may be considered in patients with a GFR < 30 ml/min/1.73 m2, especially if they have other risk factors for renal disease or if they are experiencing adverse effects from lithium treatment 5, 6.