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® 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 × 10-5), and a lithium-containing four-class combination (HR = 5.30, p = 2.46 × 10-9). The HR for lithium monotherapy was 1.82 (p = 4.73 × 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.