How to manage subtherapeutic lithium (lithium carbonate) levels?

From the Guidelines

Subclinical lithium levels typically don't require specific treatment if the patient is asymptomatic, but the dose may need to be adjusted to achieve therapeutic levels if symptoms are not adequately controlled. When managing subclinical lithium levels, it's essential to consider the patient's overall clinical presentation and response to treatment, rather than just the lithium level itself 1. The standard therapeutic range for lithium is 0.6-1.2 mEq/L, with levels below 0.6 mEq/L considered subclinical.

Key Considerations

• If a patient has subclinical levels but is responding well to treatment, no intervention may be necessary, but regular monitoring of lithium levels, renal and thyroid function, and urinalyses should be performed every 3-6 months 1.
• If symptoms of the underlying condition (typically bipolar disorder) are not adequately controlled, the lithium dose should be gradually increased under medical supervision, for example, by 150-300 mg per day every 5-7 days until therapeutic levels are achieved, with regular blood monitoring.
• Ensure the patient takes lithium consistently with meals at the same times daily to maintain stable levels, and advise them to maintain adequate hydration (2-3 liters of water daily) and consistent salt intake.
• Patients should avoid NSAIDs, diuretics, and ACE inhibitors which can affect lithium levels, and regular monitoring of thyroid and kidney function is essential even with subclinical levels, as lithium can affect these organs over time 1.

Monitoring and Adjustments

• Regular monitoring of lithium levels, renal and thyroid function, and urinalyses should be performed every 3-6 months 1.
• The goal is to find the lowest effective dose that controls symptoms while minimizing side effects, rather than targeting a specific blood level.
• Medication trials should be as systematic as possible, with the duration of trials sufficient to determine the agent's effectiveness, and a 6- to 8-week trial of a mood-stabilizing agent is recommended, using adequate doses, before adding or substituting other mood stabilizers 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Acute Mania: Optimal patient response to lithium carbonate usually can be established and maintained with 600 mg t.i.d.. Such doses will normally produce an effective serum lithium level ranging between 1 and 1. 5 mEq/L. Long-term Control: The desirable serum lithium levels are 0. 6 to 1.2 mEq/l. Dosage will vary from one individual to another, but usually 300 mg of lithium carbonate t.i.d. or q.i.d., will maintain this level.

The treatment for subclinical lithium levels is to adjust the dosage to achieve the desirable serum lithium levels of 0.6 to 1.2 mEq/L for long-term control. This can usually be achieved with 300 mg of lithium carbonate t.i.d. or q.i.d. However, dosage must be individualized according to serum levels and clinical response, and regular monitoring of the patient’s clinical state and of serum lithium levels is necessary 2.

From the Research

Treatment of Subclinical Lithium Levels

• Subclinical lithium levels can be associated with subclinical hypothyroidism, which may be caused by lithium interfering with thyroid metabolism 3.
• Lithium-induced subclinical hypothyroidism may be associated with somatic and neuropsychiatric symptoms and can interfere with treatment responsiveness 3.
• A careful assessment of thyroid function is recommended prior to initiating lithium treatment and during maintenance treatment 3.
• Guidelines for evaluation and treatment of lithium-associated subclinical hypothyroidism have been proposed, including recommendations for the threshold for initiation of thyroxine supplementation 3.

Management of Bipolar Disorder with Lithium

• Lithium is considered the gold standard for treating bipolar disorders, particularly bipolar I disorder, and its efficacy is dose-dependent and reliably correlates with serum lithium levels 4, 5, 6.
• The ideal time for sample collection to measure serum lithium levels is just before the next dose, and for once-daily dosing, it is recommended to estimate serum lithium levels at 24 hours post-the last dose 4.
• Lithium may be effective in treating acute mania and preventing both manic and depressive episodes, and its efficacy is maximized when used to prevent relapse 5, 6.
• Combination therapy with lithium and valproate may be more effective than monotherapy with either drug alone for relapse prevention in bipolar I disorder 7.