Diabetes mellitus risk for 102 drugs and drug combinations used in patients with bipolar disorder.

OBJECTIVE: To compare the largest set of bipolar disorder pharmacotherapies to date (102 drugs and drug combinations) for risk of diabetes mellitus (DM). METHODS: The IBM MarketScan® database was used to retrospectively analyze data on 565,253 adults with bipolar disorder without prior glucose metabolism-related diagnoses. The pharmacotherapies compared were lithium, mood-stabilizing anticonvulsants, antipsychotics, and antidepressants (monotherapy and multi-class polypharmacy). Cox regression modeling included fixed pre-treatment covariates and time-varying drug exposure covariates to estimate the hazard ratio (HR) of each treatment versus "No drug". RESULTS: The annual incidence of new-onset diabetes during the exposure period was 3.09 % (22,951 patients). The HR of drug-dependent DM ranged from 0.79 to 2.37. One-third of the studied pharmacotherapies, including most of the antipsychotic-containing regimens, had a significantly higher risk of DM compared to "No drug". A significantly lower DM risk was associated with lithium, lamotrigine, oxcarbazepine and bupropion monotherapies, selective serotonin reuptake inhibitors (SSRI) mono-class therapy and several drug combinations containing bupropion and an SSRI. As additional drugs were combined in more complex polypharmacy, higher HRs were consistently observed. CONCLUSIONS: There is an increased risk of diabetes mellitus associated with antipsychotic and psychotropic polypharmacy use in bipolar disorder. The evidence of a lower-than-baseline risk of DM with lamotrigine, oxcarbazepine, lithium, and bupropion monotherapy should be further investigated.

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.

Preschool Assessment of Preterm Infants Treated With Darbepoetin and Erythropoietin.

BACKGROUND: We previously reported improved neurodevelopmental outcomes at 2 years among infants treated with the erythropoiesis-stimulating agents (ESAs) darbepoetin alfa (darbepoetin) or erythropoietin. Here we characterize 4-year outcomes. METHODS: Former preterm infants randomly assigned to receive darbepoetin (10 µg/kg, once per week), erythropoietin (400 U/kg, 3 times/week), or placebo through 35 weeks' postconceptual age were evaluated at 3.5 to 4 years of age. For comparison, healthy children formerly delivered full term (term controls [TCs]) were also recruited. All participants were assessed by using measures of full-scale IQ (FSIQ) and general language from the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, and an overall measure of executive function, on the basis of tests evaluating inhibitory control and spatial working memory. Rates of neurodevelopmental impairment were compared across groups. RESULTS: Multivariate analysis of variance compared children randomly assigned to ESAs (n = 39), placebo (n =14), and TCs (n = 24). FSIQ and performance IQ were significantly higher in the ESA group than in the placebo group (FSIQ: 91.1 ± 17.5 vs 79.2 ± 18.5, P = .036; performance IQ: 93.0 ± 17.0 vs 79.5 ± 19.5, P = .018). Follow-up analyses revealed that the children receiving ESAs performed better than those who received placebo on executive function tasks. The ESA group's performance was below that of TCs, but the results did not reach significance on executive function. The incidence of neurodevelopmental impairment was greater in the placebo group than in the ESA group. CONCLUSIONS: ESA-treated infants had better cognitive outcomes and less developmental impairment at 3.5 to 4 years of age compared with placebo-treated infants. ESAs show promise in improving long-term cognitive outcomes of infants born prematurely.