From the Guidelines
A normal morning lithium serum level does not rule out lithium toxicity, especially when the blood was drawn many hours after the last evening dose. Lithium levels fluctuate throughout the day, with peak concentrations occurring 1-3 hours after oral administration and the lowest levels typically occurring just before the next dose 1. This morning trough level might miss toxicity that occurs at peak concentration. To accurately assess for lithium toxicity, clinical symptoms must be considered alongside laboratory values. Signs of toxicity include tremor, ataxia, confusion, slurred speech, nausea, vomiting, diarrhea, and in severe cases, seizures or coma.
Key Considerations
- For more accurate monitoring, blood samples should ideally be drawn 12 hours after the last dose.
- Certain conditions like dehydration, decreased sodium intake, renal impairment, or drug interactions can increase lithium levels and cause toxicity even when routine measurements appear normal 1.
- If lithium toxicity is suspected despite normal morning levels, consider checking a level closer to peak time or monitoring the patient for clinical manifestations of toxicity.
Monitoring and Prevention
- Regular monitoring of GFR, electrolytes, and drug levels is recommended for people taking potentially nephrotoxic agents such as lithium 1.
- Maintaining hydration during intercurrent illness and avoiding concomitant NSAIDs can help prevent lithium toxicity 1.
From the FDA Drug Label
Blood samples for serum lithium determination should be drawn immediately prior to the next dose when lithium concentrations are relatively stable (i.e., 8-12 hours after the previous dose). Patients abnormally sensitive to lithium may exhibit toxic signs at serum levels of 1 to 1. 5 mEq/l. Total reliance must not be placed on serum levels alone. Accurate patient evaluation requires both clinical and laboratory analysis.
Lithium toxicity assessment should consider both serum levels and clinical evaluation.
- A normal serum lithium level in the morning, after an evening dose, does not rule out lithium toxicity because:
- Serum levels may not be stable at this time point.
- Some patients may exhibit toxic signs at serum levels within the normal range.
- Clinical evaluation is also necessary for accurate assessment. 2
From the Research
Assessing Lithium Toxicity
- Lithium toxicity can occur even when serum levels are within the normal range 3
- The serum lithium level does not necessarily detect an intoxication, and clinical signs of intoxication should be taken into account when assessing for lithium toxicity 3
- Factors that increase the probability of developing signs of lithium intoxication include advanced age, co-morbidity with pre-existing neurological or other general diseases, and combination with other medications such as antipsychotics, antidepressants, or mood stabilizers 3
Normal Serum Levels and Lithium Toxicity
- Normal serum lithium levels do not rule out lithium toxicity, as intoxications can occur even at normal serum levels 3
- In patients developing signs of intoxication under lithium therapy, further investigations should include serum levels and an EEG, regardless of the serum lithium level 3
- Discontinuation of lithium medication should be considered based on clinical signs of intoxication, even if serum levels are within the normal range 3
Renal Complications and Lithium Toxicity
- Lithium treatment is associated with renal side effects, including nephrogenic diabetes insipidus, chronic tubulointerstitial nephropathy, and acute kidney injury (AKI) 4, 5, 6, 7
- The development of chronic kidney disease (CKD) seems to be associated with lithium therapy duration, and the underlying pathology, such as focal segmental glomerulosclerosis (FSGS), can contribute to CKD progression 7