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Lithium, anticonvulsants may increase rate of chronic kidney disease

Maintenance treatment with lithium or anticonvulsants was associated with an increased rate of chronic kidney disease, however, lithium was not associated with an increased rate of end-stage chronic kidney disease, according to recent findings.

“Lithium has for more than 60 years been the main mood stabilizing treatment for bipolar disorder, and the evidence for a prophylactic effect of lithium is strong and still increasing. Unfortunately, the potential adverse effects of lithium have always been an issue; among these, the possible effect of long-term lithium treatment on renal function has given rise to considerable concern,” Lars Vedel Kessing, MD, DMSc, of the University of Copenhagen, Rigshospitalet, Copenhagen, and colleagues wrote. “With results from the 3 most recent and largest controlled studies, it is still controversial whether the protracted use of lithium can cause progressive deterioration in renal function, culminating in renal failure.

To assess rates of chronic kidney disease — particularly end-stage disease — among individuals exposed to lithium, anticonvulsants and other medications used for bipolar disorder, researchers analyzed a Danish nationwide population-based sample of more than 1.5 million individuals across two cohorts. The first cohort included 1.5 million individuals registered in Denmark, 10,591 individuals diagnosed with a single manic episode or bipolar disorder, 26,731 individuals exposed to lithium and 420,959 exposed to anticonvulsants. The second cohort included a subgroup of 10,591 individuals diagnosed with bipolar disorder.

Overall, possible chronic kidney disease was diagnosed in 0.8% of the first cohort and 2.6% of the second cohort.

Definite chronic kidney disease was diagnosed in 1% of the first cohort and 3% of the second cohort.

End-stage chronic kidney disease was diagnosed in 0.2% of the first cohort and 0.6% of the second cohort.

Based on total sample and not considering diagnoses, lithium use was associated with an increased rate of definite chronic kidney disease (0 prescription HR = 1.09; 95% CI, 0.81-1.45; ≥60 prescriptions HR = 3.65; 95% CI, 2.64-5.05; P < .001). Further, lithium use was associated with an increased rate of possible chronic kidney disease (0 prescription HR = 1.01; 95% CI, 0.79-1.3; ≥60 prescriptions HR = 2.88; 95% CI, 2.17-3.81; P < .001).

Use of anticonvulsants, antipsychotics and antidepressants were not associated with an increased rate for definite or possible chronic kidney disease.

Increased rates of end-stage chronic kidney disease were not associated with use of lithium or any other drug class.

Among individuals with bipolar disorder, lithium use was associated with an increased rate of definite chronic kidney disease (P < .001) or possible chronic kidney disease (P < .001), as were anticonvulsants (P < .001).

Researchers did not find this association for antipsychotics or antidepressants.

Anticonvulsants were associated with an increased rate of end-stage chronic kidney disease among individuals with bipolar disorder (P = .002), whereas lithium was not.

“Monitoring of both lithium levels and renal function continues to be essential, especially in elderly individuals, although the optimal frequency is not established. The other psychotropic drugs used in the long term are probably safe alternatives to lithium, but clarification in the bipolar population would be welcome. Good practice will aim for doses of lithium giving levels at the lower end of the 0.6- to 0.8-mEq/L range, and not higher, especially in women,” Guy M. Goodwin, FMedSci, of the University of Oxford, England, wrote in an accompanying editorial. “So, should we continue to use lithium? Given its effectiveness in reducing relapse and suicide, certainly we should.” – by Amanda Oldt

Disclosure: Kessing reports consultant roles for Lundbeck and AstraZeneca in the past three years. Goodwin reports holding shares in P1vital and consultant, advisory, or continuing medical education speaker roles during the last 2 years for AstraZeneca, Abbvie, Cephalon/Teva, Convergence, Eli Lilly and Co, GlaxoSmithKline, Lundbeck, Medscape, Merck, Otsuka, P1vital, Servier, Sunovion, and Takeda. Please see the full study for a list of all authors’ relevant financial disclosures.