Use of Antipsychotic Medications in Non-Substance-Related Delirium—the Gap Between Research Findings and Clinical Practices

Purpose of the review Gaps exist between the research knowledge base and clinical practices pertaining to the use of antipsychotics in delirium. We reviewed 19 major randomized studies on the use of antipsychotics in non-substance-related delirium to understand factors contributing to this gap. Recent findings Based on limited literature, antipsychotics are not effective in treating delirium in patients who are mechanically ventilated intensive care unit patients and those in palliative care, but they may be effective in preventing delirium in high-risk patients after elective surgery. The literature on the use of antipsychotics for delirium in general hospital patients is less clear. Summary Delirium is a complex and heterogeneous syndrome and is influenced by several individual and clinical factors, which make researching its pharmacological treatment very difficult. Furthermore, heterogeneity of the studies is a barrier to reliable meta-analyses. Until methodologically sound literature pertinent to specific patient populations and clinical scenarios accumulates, we should use both the research literature and clinical expertise to formulate practice guidelines

Erythromycin, QTc interval prolongation, and torsade de pointes:Case reports, major risk factors and illness severity

OBJECTIVES: Erythromycin is a macrolide antibiotic that is widely used for various infections of the upper respiratory tract, skin, and soft tissue. Similar to other macrolides (clarithromycin, azithromycin), erythromycin has been linked to QTc interval prolongation and torsade de pointes (TdP) arrhythmia. We sought to identify factors that link to erythromycin-induced/associated QTc interval prolongation and TdP. METHODS AND RESULTS: In a critical evaluation of case reports, we found 29 cases: 22 women and 7 men (age range 18–95 years). With both oral and intravenous erythromycin administration, there was no significant relationship between dose and QTc interval duration in these cases. Notably, all patients had severe illness. Other risk factors included female sex, older age, presence of heart disease, concomitant administration of either other QTc prolonging drugs or agents that were substrates for or inhibitors of CYP3A4. Most patients had at least two risk factors. CONCLUSIONS: On the basis of case report evaluation, we believe that major risk factors for erythromycin-associated TdP are female sex, heart disease and old age, particularly against a background of severe illness. Coadministration of erythromycin with other drugs that inhibit or are metabolized by CYP3A4 or with QTc prolonging drugs should be avoided in this setting

Azithromycin, cardiovascular risks, QTc interval prolongation, torsade de pointes, and regulatory issues:A narrative review based on the study of case reports

Over the past year, three articles have appeared in the New England Journal of Medicine describing conflicting findings about azithromycin and cardiac safety, particular azithromycin-induced QTc interval prolongation and torsade de pointes. The FDA wants healthcare providers to consider azithromycin-induced fatal cardiac arrhythmias for patients already at risk for cardiac death and other potentially arrhythmogenic cardiovascular conditions. In a systematic review of case reports we sought to determine factors that link to azithromycin-induced/associated QTc interval prolongation and torsade de pointes. We found 12 cases: seven female and five male. Of the nine adults with reported azithromycin doses, concurrent QTc interval measurement, and without congenital long QT syndrome, we found no significant relationship between dose and QTc interval duration. Additional risk factors were female sex, older age, heart disease, QTc interval prolonging drugs and metabolic inhibitors, hypokalemia, and bradycardia. All 12 subjects had at least two additional risk factors. Elderly women with heart disease appear to be at particularly risk for drug-related QTc interval prolongation and torsade de pointes

Clarithromycin, QTc interval prolongation and torsades de pointes:the need to study case reports

BACKGROUND: The manufacturers of clarithromycin sought a drug similar in efficacy to erythromycin but with a superior side-effect profile. They generally achieved this outcome, but postmarketing findings identified a series of reports linking clarithromycin to QTc interval prolongation and torsades de pointes (TdP) ultimately leading to a Black Box Warning. We sought to clarify risk factors associated with TdP among case reports of patients receiving clarithromycin linked to QTc interval prolongation and TdP. METHODS AND RESULTS: In a detailed literature search, we found 15 women, five men, and one boy meeting our search criteria. Among the 17 adults with reported clarithromycin dose and concurrent QTc interval measurement, we found no statistically significant relationship between clarithromycin dose and QTc interval duration. This did not change for the adults who developed TdP. Among adults, major risk factors were female sex (15), old age (11) and heart disease (17). A total of eight adult subjects had all three major risk factors and 14 of the 20 adults had at least two major risk factors. All adult subjects had at least two risk factors besides clarithromycin. A total of four of the 20 adults received cisapride and three received disopyramide. Three adults were considered to suffer from some aspect of the congenital long QT syndrome. CONCLUSIONS: We believe that the risk factor description for this drug should be refined to emphasize the major risk factors of (1) female sex, (2) old age and (3) heart disease