Serum Lithium Fluctuations Reduced with Sodium Chloride in Bipolar Disorder

Jun 14, 2023

Fluctuations in serum lithium during maintenance of lithium therapy in type 1 bipolar disorder may be reduced with add-on sodium chloride, according to study findings published in Bipolar Disorders.

Researchers aimed to assess the effect of add-on sodium chloride on serum lithium levels in bipolar disorder. The primary endpoint was the percentage of patients showing fluctuations in serum lithium levels (serum lithium <0.6 mEq/L or >0.8 mEq/L).

They conducted a randomized controlled trial (ClinicalTrials.gov Identifier: NCT04222816) which included 121 patients from the outpatient psychiatry department of the All India Institute of Medical Sciences, Bhubaneswar, India. Among these patients with bipolar disorder recruited from January 2020 until December 2021, 51 were excluded and 10 declined to participate. The remaining participants (18 to 60 years of age; 62% under 31 years of age; 38% women) were randomly assigned into a control group (lithium carbonate; n=30) and a test group (add-on sodium chloride [1 gm/day] with lithium carbonate; n=30).

Exclusion criteria covered a broad range of psychiatric disorders, neurotic disorders, renal, cardiovascular, neurological, endocrinal, and hepatic dysfunction, taking NSAIDs, ACE inhibitors, neuromuscular blocking agents, and depressant drugs, and a history of neurosurgical or neuropsychiatric procedures, drug or alcohol abuse, pregnant or nursing.

Control group participants received lithium carbonate with advice not to add salt at the table. Test group participants received lithium carbonate with sachets of sodium chloride (1g/day) add-on, and were advised to limit additional salt at the table to 1g/day.

Assessments were made at baseline (all patients were on maintenance lithium therapy for ≥1 month and ≤6 months) then at follow-up at weeks 4, 8, and 12 for serum lithium, sodium, potassium, serum creatinine, and aldosterone. At baseline, all patients had normal/optimum therapeutic range levels (serum sodium, 135-145 mEq/L; serum potassium, 3.5-5.0 mEq/L; serum lithium, 0.6-0.8 mEq/L). Baseline demographic and clinical characteristics showed no significant differences between groups.

A significant number of patients missed follow-up visits in the control group (3 patients at week 4, 5 at week 8, 9 at week 12), and in the test group (3 patients at week 4, 8 at week 8, 7 at week 12).

Researchers found the fluctuation rate in serum lithium in the test group (26.7%) was significantly lower (P =.01) than in the control group (63.3%). Significant variation across time was noted in the control group for serum lithium values and not in the test group. Serum lithium showed a significant difference between groups at follow-up at week 8 and week 12. All patients with fluctuating levels had a lithium level greater than 0.80 mEq/L.

Researchers noted a significant positive correlation between serum lithium and aldosterone at baseline. They found no significant differences in the change in blood pressure, creatinine clearance, aldosterone, creatinine, potassium, or serum sodium within or between groups.

Adverse events (mild) included nausea (control, 3; test, 4), thirst (control, 14; test, 12), and fine tremors (control, 18; test, 11).

Study limitations include open-label design, single-center design, and no monitoring of sinus rhythms, prolongation of intraventricular conduction, or interference with repolarization.

"Intake of add-on sodium chloride (1 g/day) may reduce the fluctuations and stabilize the serum lithium level during the maintenance phase of lithium therapy in type 1 bipolar disorder without significant alteration of sodium, potassium, aldosterone, creatinine level, and creatinine clearance," researchers concluded. They added "Psychiatrists may advise patients to take an additional 1 g of salt (at the table) per day during lithium therapy."

George S, Maiti R, Mishra BR, Jena M, Mohapatra D. Effect of regulated add-on sodium chloride intake on stabilization of serum lithium concentration in bipolar disorder: a randomized controlled trial. Bipolar Disord. Published online November 21, 2022. doi:10.1111/bdi.13276