What are the risks and benefits of using lithium (lithium carbonate) in treating bipolar disorder, particularly in patients with pre-existing renal (kidney) or thyroid conditions?

From the Guidelines

Lithium carbonate should be used with caution in patients with pre-existing renal or thyroid conditions due to its potential to worsen renal function and cause hypothyroidism, but its benefits in managing bipolar disorder can outweigh these risks with proper monitoring and dose adjustments. When considering lithium therapy, it is crucial to weigh the risks and benefits, particularly in patients with kidney or thyroid issues. For patients with renal conditions, lithium poses significant risks as it is primarily eliminated through the kidneys and can worsen renal function over time, potentially leading to nephrogenic diabetes insipidus, chronic kidney disease, or even renal failure 1. Regular monitoring of kidney function through blood tests (creatinine, BUN, eGFR) and maintaining adequate hydration are essential.

Some key points to consider when prescribing lithium include:

• Baseline laboratory assessment should include complete blood cell counts; thyroid function tests; urinalysis; blood urea nitrogen, creatinine, and serum calcium levels; and a pregnancy test in female adolescents 1.
• Once a stable lithium dose is obtained, lithium levels, renal and thyroid function, and urinalyses should be monitored regularly (every 3-6 months) 1.
• Dosing typically starts lower (300mg daily) with more frequent monitoring in patients with pre-existing renal conditions.
• For those with thyroid conditions, regular thyroid function tests (TSH, T4) are necessary, typically every 3-6 months, as lithium commonly causes hypothyroidism by inhibiting thyroid hormone release.
• Alternative mood stabilizers like valproate or lamotrigine may be considered for patients with significant renal or thyroid impairment, though these carry their own side effect profiles 1.

Despite the potential risks, lithium offers substantial benefits including prevention of both manic and depressive episodes, reduction of suicide risk, and neuroprotective effects. The therapeutic range is narrow (0.6-1.2 mEq/L), requiring regular blood level monitoring. The decision to use lithium should balance its proven efficacy against individual risk factors through careful monitoring and dose adjustments, as recommended in the practice parameter for the assessment and treatment of children and adolescents with bipolar disorder 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. Lithium is indicated in the treatment of manic episodes of Bipolar Disorder. Maintenance therapy reduces the frequency of manic episodes and diminishes the intensity of those episodes which may occur.

The benefits of lithium in treating bipolar disorder include:

• Normalization of symptomatology within 1 to 3 weeks in patients experiencing a manic episode
• Reduction of frequency of manic episodes
• Diminishment of intensity of manic episodes

The risks of lithium, particularly in patients with pre-existing renal or thyroid conditions, include:

• High risk of lithium toxicity in patients with significant renal disease
• Need for extreme caution, daily serum lithium determinations, and low doses in patients with pre-existing conditions
• Necessity of hospitalization in patients with life-threatening psychiatric indications and pre-existing conditions 2

From the Research

Risks of Lithium Treatment

• Renal effects: Lithium treatment may reduce glomerular filtration rate and urinary concentrating ability, increasing the risk of renal failure, although the absolute risk is small 3.
• Thyroid effects: Lithium is associated with an increased risk of hypothyroidism, with a prevalence of clinical hypothyroidism increased in patients taking lithium compared to those given placebo 3.
• Parathyroid effects: Lithium treatment is associated with increased blood calcium and parathyroid hormone levels, indicating hyperparathyroidism 3.
• Weight gain: Patients receiving lithium may experience weight gain, with an odds ratio of 1.89 compared to those receiving placebo 3.
• Neurological effects: Lithium treatment may cause tremor, extrapyramidal symptoms, and cognitive disturbances, although severe neurological sequelae are exceptional 4.

Benefits of Lithium Treatment

• Effective treatment for bipolar disorder: Lithium is a widely used and effective treatment for mood disorders, particularly bipolar disorder 3.
• Mood stabilization: Lithium has been shown to be effective in stabilizing mood and preventing relapse in patients with bipolar disorder 4.

Special Considerations

• Patients with pre-existing renal conditions: Lithium treatment may exacerbate renal impairment, and patients with pre-existing renal conditions should be monitored closely 5, 4.
• Patients with pre-existing thyroid conditions: Lithium treatment may affect thyroid function, and patients with pre-existing thyroid conditions should be monitored closely 6, 4.
• Drug interactions: Lithium may interact with other medications, such as diuretics and nonsteroidal anti-inflammatory drugs, which may increase the risk of lithium toxicity 5.
• Pregnancy and breastfeeding: Lithium is rated as category D during pregnancy, and its use should be avoided unless the benefit to the mother exceeds the risk to the fetus 4. The safety of lithium during breastfeeding is controversial, and its use should be approached with caution 4.