Contraindications to Starting Lithium Therapy
Lithium should not be prescribed to patients with significant renal or cardiovascular disease, severe debilitation, dehydration, sodium depletion, or those receiving diuretics due to the very high risk of lithium toxicity in these populations. 1
Absolute Contraindications
- Significant renal disease/impairment: Patients with compromised renal function have nearly 7 times higher risk of developing severe renal impairment (CKD stage 4-5) compared to those with normal renal function 2
- Significant cardiovascular disease: Due to increased risk of lithium toxicity 1
- Severe debilitation: Increases risk of toxicity 1
- Dehydration: Leads to increased serum lithium concentrations and toxicity 1
- Sodium depletion: Results in lithium retention and toxicity 1
- Current use of diuretics: Increases lithium retention and toxicity risk 1
- Personal or family history of medullary thyroid cancer: Based on risk of thyroid C-cell tumors 3
- Pregnancy: Animal studies suggest fetal harm, and human studies suggest potential harm but are insufficient to determine exact risk 3
Relative Contraindications (Requiring Extreme Caution)
- Older age: Elderly patients have higher risk of renal dysfunction with lithium treatment 2, 4
- Pre-existing mild renal impairment: Duration of lithium treatment is a significant risk factor for glomerular failure, with eGFR decreasing by approximately 0.64 ml/min for each year of treatment 4
- Hypothyroidism: Lithium is associated with increased risk of hypothyroidism (HR 2.31) 5
- Hypercalcemia: Lithium is associated with increased risk of raised total serum calcium (HR 1.43) 5
- Inability to comply with monitoring: Regular monitoring of lithium levels and organ function is essential 3
- Inability to maintain adequate hydration: Increases risk of toxicity 1
- Concurrent medications that interact with lithium: Particularly those affecting renal function or lithium clearance
Pre-Treatment Assessment Requirements
Before initiating lithium therapy, the following baseline assessments should be conducted:
- Renal function: Complete blood cell counts, blood urea nitrogen, creatinine, eGFR 3
- Thyroid function: TSH, T4 3
- Electrolytes: Particularly serum calcium 3, 5
- Urinalysis: To assess baseline renal function 3
- Pregnancy test: For females of reproductive age 3
- ECG: Particularly in patients over 40 or with cardiac risk factors
- Blood pressure: To assess cardiovascular status
Monitoring Requirements
If lithium is initiated despite relative contraindications, the following monitoring is essential:
- Lithium levels: Initially twice weekly during acute phase until stabilized, then every 3-6 months 3
- Renal function: Every 3-6 months 3
- Thyroid function: Every 3-6 months 3
- Calcium levels: Periodically to monitor for hypercalcemia 5
- Urinalysis: Periodically to monitor for changes 3
Special Considerations
- Women: Are at greater risk of developing renal and thyroid disorders than men, with younger women at higher risk than older women 5
- Long-term treatment: Risk of renal impairment increases with duration of treatment 4, 6
- Lithium concentration: Higher than median concentrations are associated with increased risk of adverse outcomes 5
- Hospitalization: Required if lithium must be used in patients with contraindications 1
Risk Mitigation Strategies
- Maintain lithium levels in the lower therapeutic range (preferably 0.6-0.8 mmol/L) 6
- Ensure adequate hydration and sodium intake
- Avoid concurrent medications that increase lithium levels
- Consider once-daily dosing to reduce risk of renal toxicity
- Discontinue at first sign of significant renal impairment
- Consider alternative mood stabilizers in high-risk patients
In life-threatening psychiatric situations where lithium is deemed necessary despite contraindications, treatment may be undertaken with extreme caution, including daily serum lithium determinations and adjustment to lower doses, with mandatory hospitalization 1.