What lab tests are required to monitor lithium therapy?

Laboratory Monitoring for Lithium Therapy

Monitor serum lithium levels twice weekly during acute phase until stabilized, then every 2 months during maintenance, along with baseline and periodic (every 3-6 months) renal function tests, thyroid function tests, serum calcium, and urinalysis. 1, 2, 3

Baseline Laboratory Tests Before Starting Lithium

Before initiating lithium therapy, obtain the following baseline tests to establish a reference point and identify contraindications:

• Complete blood count (CBC) 1, 2
• Thyroid function tests: TSH and free T4 1, 2
• Renal function tests: Blood urea nitrogen (BUN), creatinine, and glomerular filtration rate (GFR) 1, 2
• Serum calcium 1, 2
• Serum electrolytes 2
• Urinalysis 1, 2
• Pregnancy test in females of reproductive age 1

The FDA emphasizes that facilities must have the capability to conduct prompt and accurate serum lithium determinations before initiating therapy, as toxicity is closely related to serum concentrations and can occur at doses close to therapeutic levels. 3

Serum Lithium Level Monitoring Schedule

During Acute Phase (Treatment Initiation or Dose Adjustment)

• Check serum lithium levels twice per week until both serum levels and clinical condition stabilize 4, 2, 3
• Blood samples should be drawn 8-12 hours after the previous dose (standardized 12-hour trough level) to ensure relatively stable concentrations 3
• The therapeutic range during acute mania is 1.0-1.5 mEq/L 3

During Maintenance Therapy

• Check serum lithium levels at least every 2 months in uncomplicated cases during remission 3
• The desirable maintenance serum lithium level is 0.6-1.2 mEq/L 3
• For lithium augmentation of antidepressants, lower levels of 0.2-0.6 mEq/L may be adequate 2

Critical caveat: Toxicity risk begins at 1.5 mEq/L and serious toxicity occurs at >2.0 mEq/L. 2 Elderly patients often exhibit toxicity at levels ordinarily tolerated by others and require lower starting doses (150 mg/day). 2, 3

Ongoing Monitoring of Other Laboratory Parameters

Every 3-6 Months

• Renal function tests (BUN, creatinine, GFR) 1
• Thyroid function tests (TSH, free T4) 1
• Urinalysis 1

At Least Annually

• Serum calcium 1

The rationale for frequent renal monitoring is that chronic lithium therapy may cause diminution of renal concentrating ability, presenting as nephrogenic diabetes insipidus with polyuria and polydipsia. 3 Morphologic changes with glomerular and interstitial fibrosis have been reported in patients on chronic lithium therapy. 3

Special Monitoring Situations

Patients with Renal Impairment

• For GFR <60 mL/min/1.73 m²: Consider lower doses and more frequent monitoring 2
• For GFR <30 mL/min/1.73 m²: Reduce dose by 50% 2
• Progressive or sudden changes in renal function, even within the normal range, indicate the need for treatment reevaluation 3

During Intercurrent Illness

• Increase monitoring frequency during any acute illness 1, 2
• Maintain adequate hydration, as dehydration can lead to lithium retention and toxicity 3

When Adverse Effects Are Suspected

Early signs of lithium toxicity requiring immediate serum level testing include:

• Tremor 1
• Nausea and diarrhea 1
• Polyuria-polydipsia 1

Common adverse effects that warrant monitoring include subclinical hypothyroidism, which necessitates the regular thyroid function testing schedule. 4

Important Clinical Pitfalls

• Do not rely solely on serum levels: The FDA label explicitly states that total reliance must not be placed on serum levels alone, and accurate patient evaluation requires both clinical and laboratory analysis. 3
• Avoid NSAIDs: Concomitant use can increase lithium levels and risk of toxicity 2
• Standardize blood sampling: Always draw blood 8-12 hours after the last dose at the same time of day for consistency 3
• Monitor compliance: Research shows that 23% of patients with adverse effects had subtherapeutic levels, indicating poor adherence 5