Antipsychotics, Glycemic Disorders, and Life-Threatening Diabetic Events: A Bayesian Data-Mining Analysis of the FDA Adverse Event Reporting System (1968–2004) William DuMouchel PhD
David Fram BA
Xionghu Yang MD PhD
Ramy A. Mahmoud MD
Amy L. Grogg PharmD
Luella Engelhart MS
Krishnan Ramaswamy PhD
pages: 21 - 31
- DOI: 10.1080/10401230701844612
- Version of record first published: 22Feb2008
Background. This analysis compared diabetes-related adverse events associated with use of different antipsychotic agents. A disproportionality analysis of the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) was performed.
Methods. Data from the FDA postmarketing AERS database (1968 through first quarter 2004) were evaluated. Drugs studied included aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. Fourteen Medical Dictionary for Regulatory Activities (MedDRA) Primary Terms (MPTs) were chosen to identify diabetes-related adverse events; 3 groupings into higher-level descriptive categories were also studied. Three methods of measuring drug-event associations were used: proportional reporting ratio, the empirical Bayes data-mining algorithm known as the Multi-Item Gamma Poisson Shrinker, and logistic regression (LR) analysis. Quantitative measures of association strength, with corresponding confidence intervals, between drugs and specified adverse events were computed and graphed. Some of the LR analyses were repeated separately for reports from patients under and over 45 years of age. Differences in association strength were declared statistically significant if the corresponding 90% confidence intervals did not overlap.
Results. Association with various glycemic events differed for different drugs. On average, the rankings of association strength agreed with the following ordering: low association, ziprasidone, aripiprazole, haloperidol, and risperidone; medium association, quetiapine; and strong association, clozapine and olanzapine. The median rank correlation between the above ordering and the 17 sets of LR coefficients (1 set for each glycemic event) was 93%. Many of the disproportionality measures were significantly different across drugs, and ratios of disproportionality factors of 5 or more were frequently observed.
Conclusions. There are consistent and substantial differences between atypical antipsychotic drugs in the disproportionality reporting ratios relating to glycemic effects, especially life-threatening events, in the AERS database. The relative associational rankings of drugs are similar in reports from younger and older patients. These results agree with several other reports in the literature, do not support a “class effect” hypothesis, and provide a strong rationale for further studies to clarify the issue.