Comparison of 71 bipolar disorder pharmacotherapies for kidney disorder risk: The potential hazards of polypharmacy

Background: : This study compared the largest set of bipolar disorder pharmacotherapies to date (71 drugs and drug combinations) for risk of kidney disorders (KDs). Methods: : This retrospective observational study used the IBM MarketScan (R) database to analyze data on 591,052 adults with bipolar disorder without prior nephropathy, for onset of KDs (of moderate or high severity) following psychopharmacotherapy (lithium, mood stabilizing anticonvulsants [MSAs], antipsychotics, antidepressants), or No drug. Cox regression models included fixed pre-treatment covariates and time-varying drug exposure covariates to estimate the hazard ratio (HR) of each treatment versus No drug. Results: : Newly observed KD occurred in 14,713 patients. No regimen had significantly lower risk of KDs than No drug. The HR estimates ranged 0.86-2.66 for all KDs and 0.87-5.30 for severe KDs. As additional drugs were combined to compare more complex polypharmacies, higher HRs were consistently observed. Most regimens containing lithium, MSAs, or antipsychotics had a higher risk than No drug (p < 0.05). The risk for all and severe KDs was highest respectively on monoamine oxidase inhibitors (MAOIs) (HR = 2.66, p = 5.73 x 10(-5)), and a lithium-containing four-class combination (HR = 5.30, p = 2.46 x 10(-9)). The HR for lithium monotherapy was 1.82 (p = 4.73 x 10(-17)) for severe KDs. Limitations: : The limitations inherent for an observational study were non-randomized assignment of patients to treatment groups, non-standardization of diagnostic decisions, and non-uniform quality of data collection. No correction was made for medication dosage. Conclusions: : The findings support literature concerns about lithium nephrotoxicity and highlight the potential risks of MAOIs, MSAs, antipsychotics and psychotropic polypharmacy.