When should the first lithium level be checked in a patient with normal renal function who has recently started lithium (lithium carbonate) 150mg twice daily?

Timing of First Lithium Level After Initiation

The first lithium level should be checked at 5-7 days after starting lithium, not specifically at day 5. During the acute treatment phase, lithium levels must be monitored twice weekly until both the serum level and clinical condition stabilize 1, 2.

Standard Monitoring Protocol for Newly Initiated Lithium

Initial Monitoring Phase (First 2-4 Weeks)

• Check lithium levels twice per week during the acute phase until the patient's clinical condition and serum lithium concentration have stabilized 1, 2.
• The FDA-approved labeling explicitly states that "serum levels should be determined twice per week during the acute phase, and until the serum level and clinical condition of the patient have been stabilized" 1.
• This twice-weekly monitoring typically continues for 2-4 weeks or until therapeutic stability is achieved 2.

Timing of Blood Draw

• Draw lithium levels 12 hours after the last dose for patients on twice-daily dosing (the standard for immediate-release lithium carbonate 150mg twice daily) 1, 3.
• Blood samples must be drawn immediately prior to the next dose when lithium concentrations are relatively stable (8-12 hours after the previous dose) 1.
• For once-daily extended-release formulations, levels should still be drawn at 12 hours post-dose to compare with established therapeutic ranges, not at 24 hours 4.

Why Day 5 Specifically Is Not Evidence-Based

The question about "day 5" appears to be an oversimplification. Lithium reaches steady-state in approximately 5-7 days (based on its 18-36 hour half-life, requiring 4-5 half-lives to reach steady state) 3. However, guidelines do not specify a single "day 5" measurement but rather a twice-weekly schedule that would naturally capture levels around days 3-4 and days 7-8 1, 2.

Baseline and Concurrent Monitoring Requirements

Before initiating lithium therapy, the following baseline tests are mandatory:

• Complete blood cell counts, thyroid function tests, blood urea nitrogen, and creatinine must be obtained before starting lithium 2.
• Renal function (creatinine/eGFR) and electrolytes (particularly potassium) should be checked at baseline 2.

Target Therapeutic Range

• For acute mania, target serum lithium levels of 1.0-1.5 mEq/L are typically required, though this is achieved with 600mg three times daily in the FDA labeling, not 150mg twice daily 1.
• The dose of 150mg twice daily (300mg total) is extremely low and typically produces levels of only 0.2-0.6 mEq/L, which may be appropriate for elderly patients or augmentation strategies but is subtherapeutic for acute bipolar disorder 5.
• Most patients require 900-1800mg daily to achieve therapeutic levels for acute mania 3.

Common Pitfalls to Avoid

• Do not wait until "day 5" as a single checkpoint—implement twice-weekly monitoring from the start of therapy 1.
• Do not rely solely on serum levels—the FDA labeling explicitly states "total reliance must not be placed on serum levels alone. Accurate patient evaluation requires both clinical and laboratory analysis" 1.
• Do not draw levels at random times—timing must be standardized to 12 hours post-dose for meaningful interpretation 1, 3.
• Patients with reduced renal function (eGFR <60 mL/min/1.73 m²) require more frequent monitoring than standard protocols 2, 6.
• Monitor for drug interactions, particularly NSAIDs, ACE inhibitors, ARBs, and thiazide diuretics, which can increase lithium levels and require more frequent monitoring 2, 5.

Transition to Maintenance Monitoring

• Once stable, lithium levels should be monitored at least every 2 months during uncomplicated maintenance therapy 1.
• The American Academy of Child and Adolescent Psychiatry recommends monitoring every 3-6 months during stable maintenance therapy 2.
• Increase monitoring frequency to 1-2 weeks after any dose adjustments, addition of interacting medications, changes in renal function, or significant weight changes 2.