Journal Article Annotations
2023, 1st Quarter

Pyschonephrology

Annotations by Sahil Munjal, MD
April, 2023

Real-World Clinical Practice Among Patients With Bipolar Disorder and Chronic Kidney Disease on Long-term Lithium Therapy.

PUBLICATION #1 — Pyschonephrology

Real-World Clinical Practice Among Patients With Bipolar Disorder and Chronic Kidney Disease on Long-term Lithium Therapy

Rakesh Kumar, Boney Joseph, Vanessa M Pazdernik, Jennifer Geske, Nicolas A Nuñez, Mehak Pahwa, Kianoush B Kashani, Marin Veldic, Hannah K Betcher, Katherine M Moore, Paul E Croarkin, Aysegul Ozerdem, Alfredo B Cuellar-Barboza, Susan L McElroy, Joanna M Biernacka, Mark A Frye, Balwinder Singh.

Abstract: J Clin Psychopharmacol. 2023 Jan-Feb;43(1):6-11. doi: 10.1097/JCP.0000000000001632.

Purpose:
Long-term lithium therapy (LTLT) has been associated with chronic kidney disease (CKD). We investigated changes in clinical characteristics, pharmacotherapeutic treatments for medical/psychiatric disorders, and outcomes among patients with bipolar disorder (BD) and CKD on LTLT in a 2-year mirror-image study design.

Methods:
Adult BD patients on LTLT for ≥1 year who enrolled in the Mayo Clinic Bipolar Disorder Biobank and developed CKD (stage 3) were included, and our study was approved by the Mayo Clinic Institutional Review Board. The primary outcome was the time to the first mood episode after CKD diagnosis among the lithium (Li) continuers and discontinuers. Cox proportional hazards models were used to estimate the time to the first mood episode. We tested for differences in other medication changes between the Li continuers and discontinuers group using Mantel-Haenszel χ2 tests (linear associations).

Results:
Of 38 BD patients who developed CKD, 18 (47%) discontinued Li, and the remainder continued (n = 20). The median age of the cohort was 56 years (interquartile range [IQR], 48-67 years), 63.2% were female, and 97.4% were White. As compared with continuers, discontinuers had more psychotropic medication trials (6 [IQR, 4-6] vs 3 [IQR, 2-5], P = 0.02), a higher rate of 1 or more mood episodes (61% vs 10%, P = 0.002), and a higher risk of a mood episode after CKD diagnoses (Hazard Ratio, 8.38; 95% confidence interval, 1.85-38.0 [log-rank P = 0.001]].

Conclusions:
Bipolar disorder patients on LTLT who discontinued Li had a higher risk for relapse and a shorter time to the first mood episode, suggesting a need for more thorough discussion before Li discontinuation after the CKD diagnosis.

Annotation

The finding:
This study examined adult bipolar patients on long term lithium therapy (>1yr) who developed chronic kidney disease (CKD) stage 3. Patients who discontinued lithium were compared to those who continued lithium two years post-CKD diagnosis. For discontinuers, time to the first mood episode was significantly shorter and the likelihood of a mood episode was significantly increased (61% vs 10%).

Strength and weaknesses:
A study strength was that it was a mirror-image study design in which patients served as their own controls, comparing previous and subsequent treatment periods, which minimized multiple confounding variables. Weaknesses included the observational study design with a small sample size (n=38) and a short duration follow up of two years.

Relevance:
It is well known that lithium remains the gold standard when it comes to treatment of bipolar disorder. However, it remains underutilized, in part of its well-established association with worsening kidney function. For patients on long term lithium that have already developed CKD, controversy remains as to the next steps. This study adds to a growing list of evidence pointing towards worsening mental health outcomes in lithium discontinuers. The authors do highlight strategies to minimize lithium’s adverse kidney effects by avoiding nephrotoxins, maintaining low serum levels, once a day dosing of lithium and regular monitoring of kidney function. CL psychiatrists should discuss the increased risk of mood destabilization in patients considering lithium discontinuation.

Type of study (EBM guide):
Cohort study