Research has shown that depression increases the likelihood that otherwise healthy people will develop ischemic heart disease (IHD) and worsens the prognosis of patients who already have IHD. Moreover, concerns about safety (e.g., cardiac side effects, drug-drug interactions) have caused physicians to be hesitant about using antidepressant agents in patients with IHD. This article is based on a recent roundtable of experts who met to discuss risk, diagnosis, and treatment options for depression in patients with IHD. This article reviews clinical and epidemiological studies that have described a link between depression and the subsequent development of IHD and have examined the role of depression as a predictor of cardiac events in patients with existing IHD. The article addresses the issue of whether depression can be safely and efficaciously treated both in patients with stable IHD and in those with acute coronary syndromes. The authors discuss safety issues related to the potential for interactions between antidepressants and cardiovascular medications, the use of nonpharmacologic treatment options such as psychosocial interventions, and the effect of antidepressant therapy on quality of life in patients with IHD. The article concludes with practical clinical guidance concerning the management of depression in patients who have recently experienced myocardial infarction.
The authors review the mechanisms and establish the risk of torsade de pointes and sudden death with antipsychotic drugs.They present a review of original concepts, the distinction between familial and drug-induced cases of torsade de pointes, and the recognition of the role of noncardiac drugs in torsade de pointes and sudden death. They review the evidence linking QTc interval prolongation, potassium channels, and torsade de pointes from both the long QT syndrome and drugs. They examine the risk for torsade de pointes from antipsychotic drugs and estimate the frequency of sudden death on the basis of epidemiological data in normal and schizophrenic populations.All drugs that cause torsade de pointes prolong the QTc interval and bind to the potassium rectifier channel, but the relationships are not precise. Prediction of torsade de pointes and sudden death can be improved by examining dose dependency, the percent of QTc intervals higher than 500 msec, and the risk of drug-drug interactions. Although sudden unexpected death occurs almost twice as often in populations treated with antipsychotics as in normal populations, there are still only 10-15 such events in 10,000 person-years of observation.Although pimozide, sertindole, droperidol, and haloperidol have been documented to cause torsade de pointes and sudden death, the most marked risk is with thioridazine. There is no association with olanzapine, quetiapine, or risperidone. Ziprasidone does prolong the QT interval, but there is no evidence to suggest that this leads to torsade de pointes or sudden death. Only widespread use will prove if ziprasidone is entirely safe. To date, all antipsychotic drugs have the potential for serious adverse events. Balancing these risks with the positive effects of treatment poses a challenge for psychiatry.
In post-myocardial infarction (MI) patients, the restoration of anterograde flow in the infarct-related artery (IRA) significantly improves survival. Limitation of infarct size and increased electrical stability of the myocardium are likely operating mechanisms for this beneficial effect. We tested the hypothesis that patency of the IRA may enhance vagal reflexes, a factor known to affect electrical stability of the infarcted myocardium.Analysis of angiographic data was performed in 359 of 1284 post-MI patients enrolled in a multicenter prospective study within 8 weeks after the index MI. All the patients underwent baroreflex sensitivity (BRS) assessment by the phenylephrine method. The BRS of the entire population averaged 8.2+/-5.5 ms/mm Hg and was significantly related to age but not to ejection fraction (EF). One-, two-, and three-vessel disease was present in 138, 96, and 99 patients, respectively, while no coronary stenosis was observed in 26. IRA patency was documented in 234 patients (65%), while in the remaining 125 (35%), the artery remained occluded. Patients with occluded IRAs had more extensive coronary disease (2 to 3 vessels, 71% versus 46%, P<.01) and more depressed left ventricular (LV) function (LVEF, 48+/-13% versus 53+/-12%, P<.001). Patency of the IRA was associated with higher BRS values (BRS, 8.9+/-5.8 versus 7.1+/-4.7 ms/mm Hg, P<.005) and with a lower incidence (9% versus 18% P<.02) of markedly depressed BRS (<3 ms/mm Hg), a condition suggested by preliminary studies to be associated with an increased risk of post-MI mortality. The association between IRA patency and BRS was more evident in anterior than in inferior MI. Multivariate regression analysis showed that age of the patient and patency of the IRA were the major independent determinants of BRS, while LVEF was weakly related to BRS and only when analyzed as a categorized variable.The presence of an open IRA is associated with higher baroreflex sensitivity, and this effect is largely independent of limitation of infarct size by IRA patency. These data offer new insights into the mechanisms by which coronary artery patency may affect cardiac electrical stability and survival.
Abstract Central to the psychophysiologic reactivity hypothesis of the etiology of coronary artery disease is the assumption that reactivity is an individual characteristic that is stable over time. Although heart rate (HR) and blood pressure reactivity appear to meet this criterion, temporal stability of cardiac autonomic control as measured by analysis of heart period variability (HPV) has not been assessed. In this study, we tested the stability of HPV, measured in both the time and frequency domain, during a quiet, resting baseline and in response to 5‐min mental arithmetic and reaction time tasks, in 20 normal subjects measured in three testing sessions during a 9‐month period. Stability, assessed by the intraclass correlation coefficient (ICC), was excellent for resting baseline measures of HR and HPV, with ICCs of 0.68–0.86. However, HR and HPV reactivity to either arithmetic or reaction time tasks generally was less stable, with ICCs of 0.17–0.73, in contrast to results of previous studies demonstrating long‐term Stability of HR responses to psychological challenge. Stability of aggregated reactivity scores was only slightly improved. Whether for individual tasks or aggregated measures, reactivity of total and low‐frequency measures of HPV was moderately stable but stability of high‐frequency HPV reactivity was poor.
