Why avoid lithium in elderly patients with impaired renal function?

From the Guidelines

Lithium should be avoided in elderly patients with impaired renal function due to the increased risk of toxicity and adverse effects associated with decreased renal clearance. As patients age, their renal function declines, leading to reduced lithium clearance and increased serum levels, even at standard doses 1. This population is more susceptible to lithium's adverse effects, including tremor, confusion, cognitive impairment, gait disturbances, and increased fall risk. Key factors to consider in this population include:

• Decreased renal function, which reduces lithium clearance
• Altered volume distribution and decreased total body water, making them more sensitive to lithium's effects
• Polypharmacy, which increases the risk of drug interactions that can further elevate lithium levels
• Narrower therapeutic window, with toxicity potentially occurring at lower serum concentrations Regular monitoring of serum levels, renal function, thyroid function, and electrolytes is crucial if lithium is deemed necessary, with a target serum level of 0.4-0.8 mmol/L 1. Alternative mood stabilizers like valproate may be considered as first-line options in many geriatric patients with bipolar disorder. In elderly patients with impaired renal function, it is essential to weigh the benefits of lithium against the potential risks and consider alternative treatment options to minimize the risk of adverse effects. The recommendation to regularly monitor GFR, electrolytes, and drug levels in patients taking potentially nephrotoxic agents like lithium, as outlined in the 2012 KDIGO clinical practice guideline, highlights the importance of careful management in this population 1.

From the FDA Drug Label

Lithium should generally not be given to patients with significant renal or cardiovascular disease, severe debilitation or dehydration, or sodium depletion, and to patients receiving diuretics, since the risk of lithium toxicity is very high in such patients. Chronic lithium therapy may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia Lithium toxicity is closely related to serum lithium levels, and can occur at doses close to therapeutic levels

Lithium should be avoided in elderly patients with impaired renal function because the risk of lithium toxicity is very high in such patients. Impaired renal function can lead to reduced clearance of lithium, resulting in elevated serum lithium levels and increased risk of toxicity. Additionally, chronic lithium therapy can cause diminution of renal concentrating ability, which can further exacerbate renal impairment.

• Key factors to consider when evaluating the use of lithium in elderly patients with impaired renal function include:
  • Renal function: Lithium should be used with caution in patients with significant renal disease.
  • Risk of toxicity: The risk of lithium toxicity is closely related to serum lithium levels.
  • Dose adjustment: Daily serum lithium determinations and adjustment to low doses may be necessary in patients with impaired renal function 2, 2.

From the Research

Renal Function in Elderly Patients

• Elderly patients with impaired renal function may need to avoid lithium due to potential renal risks associated with its use 3, 4.
• Studies have shown that lithium use is associated with an increased risk of renal decline compared to valproate use in older adults, particularly when baseline serum lithium concentrations are higher than 0.7 mmol/L 3.
• However, other studies suggest that lithium levels up to 0.8 mmol/L may be safe for use in the long-term treatment of geriatric patients with mood disorders without pre-existing chronic renal failure 5.

Risk Factors for Renal Dysfunction

• Risk factors for renal dysfunction in geriatric patients taking lithium include age, previous lithium intoxication, polyuria, previously impaired renal function, and decreased maximal urine osmolality 6.
• Lithium duration has been found to be an independent risk factor for adverse renal outcome in patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) 4.
• Concurrent use of loop diuretics and angiotensin-converting enzyme inhibitors with lithium may also increase the risk of acute renal failure 6.

Monitoring and Alternative Medications

• Regular monitoring of renal function is recommended for geriatric patients taking lithium, with consideration of transitioning to alternative medications if poor tolerance or significant renal decline occurs 7.
• Alternative medications for bipolar disorder in geriatric patients are generally considered safe and effective, but may not have the same level of evidence as lithium 7.