Lithium Therapeutic Drug Monitoring; Once Daily Vs Twice Daily Dosing and the Impact of Kidney Function

Mount Sinai Hospital, Canada

Status: Unknown

Conditions: Major Depressive Disorder; Bipolar Disorder

Treatments: Diagnostic Test: Lithium level; Diagnostic Test: Serum Creatinine

Study type: Interventional

Funder types: Other

Identifiers

NCT03811860

18-0289-A

Details and patient eligibility

About

Lithium is a mainstay in the treatment of bipolar disorder, and a frequently used adjunctive therapy for major depressive disorder. It is accepted practice to monitor lithium serum levels to monitor for efficacy and toxicity. However, studies on the difference in lithium levels between once and twice daily dosing, which also assess the impact of kidney function are scarce. The aim of this study is to quantify this pharmacokinetic difference, identify the impact of kidney function, in the context of estimating effects to inform feasibility and sample size needed for a larger well-powered study.

Full description

Bipolar disorder is a chronic and recurring condition which causes functional impairment and increases lifetime suicide risk. Major depressive disorder likewise confers a high burden of illness on the affected population, and treatment is complicated by the fact 50-70% of patients treated with an initial agent do not achieve full remission of symptoms. There are numerous clinical practice guidelines which support the use of lithium as a first-line agent for bipolar disorder, and as an adjunctive therapy for major depressive disorder. Therapeutic ranges for lithium were established in the 1970s using multiple daily dose regimens, and therefore should not be directly applied to patients taking lithium once daily. The current standard of practice is to measure levels 12 hours post dose irrespective of once or twice daily administration. There is some evidence that lithium levels drawn 12 hours post dose are 10 - 26% higher when dosing lithium once daily compared to twice daily, however, the impact of kidney function on this difference has not been studied, and this difference in 12h post levels has not been confirmed via prospective data. Guidance on therapeutic drug monitoring (TDM) is vague with respect to interpretation of specific lithium blood levels for once daily dosing. Physicians may reduce a patient's dose based on a lithium level that is seemingly higher that target, even if the patient is clinically stable, putting the patient at risk for re-emergence of symptoms. Though it is known that lithium is excreted by the kidney, the impact of kidney function on the difference in lithium levels when dosed once daily compared to twice daily is not well understood. The results of this pilot study will help identify the impact of kidney function on lithium therapeutic drug monitoring in current practice, and potentially lead to a larger multi-center study.

Enrollment: 15 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients admitted to the inpatient psychiatry unit at Mount Sinai Hospital treated with lithium therapy (i.e. taking lithium before admission, or initiated on lithium therapy during hospitalization)

Exclusion criteria

• any patients who are currently pregnant
• patients taking lithium three times daily
• patients taking lithium with a specific dosing frequency for a documented clinical reason.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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15 participants in 2 patient groups

Once Daily Dosing

Active Comparator group

Description:

In this arm of the study, participants receive the prescribed dose of lithium once daily at bedtime. After 4-6 days, a steady state lithium serum level and serum creatinine are taken, and they crossover to the other arm (twice daily dosing, if they have not already done so). Frequency of selected medication use is noted.

Treatment:

Diagnostic Test: Serum Creatinine

Diagnostic Test: Lithium level

Twice Daily Dosing

Active Comparator group

Description:

In this arm of the study, participants receive the prescribed dose of lithium divided into two daily doses. After 4-6 days a steady state lithium serum level and serum creatinine are taken, and they crossover to the other arm (once daily dosing, if they have not already done so).Frequency of selected medication use is noted.

Treatment:

Diagnostic Test: Serum Creatinine

Diagnostic Test: Lithium level