What to do if lithium levels are normal but the patient is on a high dose of lithium citrate (lithium carbonate)?

Managing Patients with Normal Lithium Levels on High Doses

When a patient has normal serum lithium levels but is on a high dose of lithium citrate or carbonate, the medication should be maintained at the current dose if there are no signs of toxicity, but careful monitoring for clinical signs of toxicity should be implemented regardless of serum levels. 1

Understanding Lithium Levels and Dosing

Lithium has a narrow therapeutic index, with recommended serum levels typically between 0.6-0.8 mmol/L for standard formulations 1. However, it's crucial to understand that:

• Normal serum lithium levels do not always exclude toxicity 2, 3
• Dosing requirements vary significantly between individuals
• The American Psychiatric Association recommends maintenance serum lithium levels of 0.6-0.8 mmol/L, typically requiring 300 mg three to four times daily of lithium carbonate 1

Clinical Decision Algorithm

1. Assess for signs of toxicity despite normal levels:

   • Look for coarse tremor, cognitive impairment, ataxia, dysarthria, or other neurological symptoms 2
   • Check for gastrointestinal symptoms like nausea, vomiting, or diarrhea 4
   • Evaluate for excessive thirst, polyuria, or other signs of renal impact 4

2. If no signs of toxicity are present:

   • Continue current dosing if patient is clinically stable
   • Maintain regular monitoring schedule (serum levels every 2-3 months) 1
   • Consider drawing samples 12 hours after the last dose when lithium concentrations are relatively stable 1

3. If signs of toxicity are present despite normal levels:

   • Consider reducing dose or switching to a different medication 2
   • Obtain an EEG to evaluate for neurotoxicity 3
   • Assess for factors that might increase sensitivity to lithium

Risk Factors for Toxicity at Normal Serum Levels

Be particularly vigilant in patients with:

• Advanced age 3
• Pre-existing neurological conditions 3
• Renal impairment (even mild) 1, 4
• Concurrent medications (especially antipsychotics, antidepressants, or other mood stabilizers) 3
• Recent febrile illness 3
• Dehydration or electrolyte disturbances

Monitoring Recommendations

• Monitor renal function, thyroid function, and calcium levels every 3-6 months 1, 5
• Pay special attention to glomerular filtration rate, as lithium can reduce it by approximately 6.22 mL/min on average 5
• Check parathyroid hormone and calcium levels regularly due to increased risk of hyperparathyroidism 5, 4

Important Caveats

• Serum lithium levels may not reflect brain lithium concentrations, which can be 50-80% of serum levels 6
• Sustained-release formulations may require maintaining serum concentrations in the upper range (0.8-1.0 mmol/L) 6
• Case reports document severe lithium toxicity occurring despite normal serum levels 2, 3
• The timing of blood draws is critical - samples should be taken 12 hours after the last dose 1, 6

Dosage Considerations

Age-based maintenance dosing recommendations 6:

• <40 years: 25-35 mmol (925-1300 mg) daily
• 40-60 years: 20-25 mmol (740-925 mg) daily

• 60 years: 15-20 mmol (550-740 mg) daily

Remember that these are general guidelines and individual response varies significantly.