title: Antidepressants that inhibit neuronal norepinephrine reuptake are not associated with increased spontaneous reporting of cardiomyopathy.
abstract: A recent literature review linked norepinephrinergic stimulation to alterations in cyclic adenosine monophosphate (cAMP)-mediated signaling in cardiac myocytes and suggested that this might contribute to the pathological mechanisms that lead to chamber enlargement and hypocontractility, which are seen in dilated cardiomyopathy. This accompanies a large body of literature linking cardiac sympathetic outflow activation in early heart failure with progressive myocyte deterioration. As the mode of action of a number of antidepressants involves the inhibition of neuronal norepinephrine reuptake to varying degrees, this study was conducted to assess whether such agents might be associated with disproportionate reporting of cardiomyopathy. Limited data exist specifically examining the association between the antidepressant use and the cardiomyopathy. Using a data mining algorithm (DMA), we quantitatively investigated the association between antidepressant agents that predominantly exert their effects through inhibiting neuronal norepinephrine reuptake (rather than serotonin) and cardiomyopathy. We retrospectively applied a Bayesian DMA, the Bayesian Confidence Propagation Neural Network, to the cumulative reports in the Food and Drug Administration Adverse Event Reporting System (through the fourth quarter of 2006) and World Health Organization Vigibase (through the second quarter of 2007) databases. A threshold of the posterior interval 95% lower limit > 0 was used to define a signal of disproportionate reporting with individual or groups of antidepressants and cardiomyopathy-related terms. The analysis suggested that there is no direct relationship between antidepressants with greater norepinephrine reuptake inhibitor activity (affinity for norepinephrine reuptake transporter or selectivity for norepinephrine versus serotonin) and reporting of cardiomyopathy. In contrast, an inverse correlation might exist with a higher number of cases identified with tricyclic antidepressants showing lower norepinephrine reuptake inhibition and the serotonin/norepinephrine reuptake inhibitors as well as with serotonin/ norepinephrine/slight dopamine reuptake inhibitor.
authors.affiliation: Risk Management Strategy, Pfizer Global Research and Development, Sandwich, UK.
authors.forename: S
authors.initials: S
authors.lastname: Ratcliffe
authors.forename: M
authors.initials: M
authors.lastname: Younus
authors.forename: M
authors.initials: M
authors.lastname: Hauben
authors.forename: L
authors.initials: L
authors.lastname: Reich
mesh_terms: D018663:Adrenergic Agents / Q000009:adverse effects*; D016907:Adverse Drug Reaction Reporting Systems; D000465:Algorithms; D000928:Antidepressive Agents / Q000009:adverse effects*; D001499:Bayes Theorem; D009202:Cardiomyopathies / Q000139:chemically induced*; D057225:Data Mining; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects; D019317:Evidence-Based Medicine; D006801:Humans; D016571:Neural Networks, Computer; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects
chemical_list: D018663:Adrenergic Agents; D000928:Antidepressive Agents; D018765:Dopamine Uptake Inhibitors; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors