Drug therapy for bipolar disorder may lead to kidney disease
Lithium-based drugs used to treat bipolar disorder may be nephrotoxic, a recently published study by University of New Mexico Health Sciences Center researchers shows.
“There are still major inconsistencies among research findings on renal safety of [bipolar disorder] BD drugs, and the literature data is restricted to relatively few commonly used drugs/drug combinations, despite the fact that more than 50 medications are currently prescribed in the U.S. to treat mood disorders, plus an unknown number of combinations,” Anastasiya Nestsiarovicha, MD, of the department of internal medicine and the University’s Center for Global Health, and colleagues wrote. “Despite decades of scientific investigation, doubts still remain on both the existence and the magnitude of lithium-induced kidney impairment. Major concerns remain on the potential of lithium to induce acute kidney injury and end-stage renal disease (ESRD) during long-term use.”
Nestsiarovicha and colleagues analyzed data from 591,052 commercially insured adults with bipolar disorder treated with psychopharmacotherapy from 2003 to 2015 without a diagnosis of kidney disease and then followed up after psychopharmacotherapy was administered. The drug regimens for treating bipolar disorder included lithium, mood-stabilizing anticonvulsants (MSAs), antipsychotics and antidepressants. Patients who did not receive any psychopharmacotherapy were also included in the analysis. Researchers identified 71 drugs and drug combinations prescribed to patients during the 12-year period.
Results showed new cases of kidney disease occurred in 14,713 patients (2.5%) treated with pharmacotherapy. Patients who used monoamine oxidase inhibitors (MAOIs) and a lithium-containing four-class combination had the greatest risk for kidney disease, the researchers wrote.
One-third of the patients who did have kidney disease after taking drugs to treat their bipolar disorder had what the researchers called “high severity” kidney disease. These patients had kidney disease that was “life-threatening and debilitating [with] potential and probable irreversibility.” That included those with ESRD, crescentic/rapidly progressive glomerulonephritis, acute or “unspecified” kidney failure, chronic kidney disease of stage 4 or stage 5 or “unspecified,” kidney sclerosis, kidney cortical/medullary necrosis, and terminal atrophy of kidney. Patients who were on dialysis or had a kidney transplant were also included in this list as indicators of ESRD.
Those categorized as having “moderate” severity kidney disease included all other not-excluded kidney conditions, including acute and chronic glomerulonephritis, having stage 2 and stage 3 CKD, nephritic and nephrotic syndromes (but not with crescentic glomerulonephritis), tubulointerstitial nephritis, drug/metal-induced and toxic nephropathy.
“The findings support literature concerns about lithium nephrotoxicity and highlight the potential risks of MAOIs, MSAs, antipsychotics and psychotropic polypharmacy,” the authors wrote. – by Mark E. Neumann
Disclosures: Funding for this study was provided by a Patient-Centered Outcomes Research Institute award (CER-1507-3160) and was part of a research project, “Longitudinal comparative effectiveness of bipolar disorder therapies” (ClinicalTrials.gov identifier: NCT02893371). Please see the study for all other authors’ relevant financial disclosures.