Should lithium levels be checked at trough or randomly in patients on lithium therapy?

Lithium Levels Should Be Checked at Trough, Not Randomly

Lithium levels should always be drawn as trough concentrations, meaning immediately before the next scheduled dose (12 hours after the last dose for twice-daily regimens or 24 hours after the last dose for once-daily regimens). 1

Rationale for Trough Monitoring

Lithium has a narrow therapeutic index, making precise monitoring essential for both efficacy and safety. The FDA label explicitly states that "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)" 1. This approach ensures consistent and comparable measurements across time.

Timing Based on Dosing Schedule

The appropriate timing for lithium level measurement depends on the dosing regimen:

• Multiple daily doses: Draw levels 12 hours after the last dose, just before the next scheduled dose 1, 2
• Once-daily dosing: Draw levels 24 hours after the last dose, immediately before the next dose 2, 3

Research by Venkatasubramanian et al. found that lithium levels measured at 12 hours were approximately 1.3 times higher than the actual trough levels at 24 hours in patients on once-daily dosing 3. This significant difference could lead to inappropriate dosage adjustments if not properly timed.

Pharmacokinetic Considerations

Lithium has a half-life of 18-36 hours and reaches peak plasma concentrations at different times depending on the formulation:

• Standard-release: 1-2 hours after administration
• Sustained-release: 4-5 hours after administration 2

These variations in absorption and distribution make trough measurements the most reliable indicator of steady-state lithium concentration.

Clinical Implications

Measuring lithium at non-trough times can lead to:

1. Falsely elevated readings if measured near peak concentration
2. Inappropriate dose reductions based on these elevated readings
3. Subtherapeutic treatment and potential relapse

A study by Venkatasubramanian et al. demonstrated that patients on once-daily lithium regimens could be maintained on inappropriately low doses if levels were measured at 12 hours rather than at the true trough (24 hours) 3.

Target Therapeutic Ranges

When properly measured at trough, target lithium levels should be:

• Acute mania: 1.0-1.5 mEq/L
• Long-term maintenance: 0.6-1.2 mEq/L 1

Some experts now recommend maintaining levels between 0.6-0.8 mmol/L for maintenance therapy, though others still favor 0.8-1.2 mmol/L 2.

Monitoring Frequency

• During acute phase: Measure twice weekly until stabilization 1
• During maintenance: Check levels at least every two months 1
• After dosage changes: Check levels 5-7 days after adjustment 4

Practical Tips for Accurate Measurement

1. Ensure patient has been on a stable dose for at least 5-7 days before measurement
2. Draw blood exactly at the trough time point
3. Maintain consistent timing for serial measurements
4. Document the time of last dose and time of blood draw
5. Consider suspending lithium during illness or before procedures requiring NPO status 4

Accurate lithium monitoring is essential for both efficacy and safety. Using standardized trough measurements provides the most reliable basis for clinical decision-making and dosage adjustments.