CARDIOVASCULAR EFFECTS OF TCAS IN CHILDREN AND ADULTS

Despite the recent introduction of new antidepressant agents, pharmacologic treatment of both child and adult psychiatric disorders continues to rely on the use of the tricyclic antidepressants (TCA's). The most serious side effects of TCA's are those affecting the cardiovascular system. Current understanding of these cardiovascular effects is derived largely from studies of middle-aged and older adults with depression. However, studies of other populations suggest that ae has a pronounced influence on the cardiovascular effects of TCA's and that, in younger individuals, TCA's are much more likely to produce significant increases in lying blood pressure and marked increases in heart rate. In the last several years, five cases of sudden death, presumably secondary to cardiac arrhythmias, have been reported in children and adolescents being treated with TCAs. Much of the speculation about the possible role of TCA's in precipitating arrhythmias in these cases has implicitly assumed that the salient effects of TCA's in children are the same as those associated with the development of adverse cardiac events in older adults; for example, one area of concern has been the TCA-induced prolongation of intracardiac conduction and the development of heart block. However, it is possible that effects of TCAs which are responsible for increases in heart rate and blood pressure in young people play a role in altering the vulnerability to serious arrhythmias. The proposed studies will obtain critical information on the effect of age on the cardiovascular effects of TCA's. Specifically, over three years, the cardiovascular effects of a widely-used TCA, desipramine (DMI), will be examined in 80 children and adolescents with Attention- Deficit/Hyperactivity Disorder and in 40 young and older adults with major depression. At baseline and after three weeks on DMI, lying and standing pulse and blood pressure, measures of sympathetic and parasympathetic activity, and 24-hour ambulatory monitoring of cardiac rhythm will be obtained. It is hypothesized that, in children and adolescents, the use of DMI will be associated with a substantial increase in the ration of sympathetic to parasympathetic input to the heart, a change which is associated with increased vulnerability to ventricular arrhythmias in other populations.