Is doxepin a safer tricyclic for the heart?

BACKGROUND Many clinicians believe that doxepin is the safest tricyclic with respect to cardiovascular effects. This belief has persisted for two decades despite the absence of rigorous prospective evaluation. METHOD To address this issue, the authors studied the cardiovascular effects of doxepin in 32 depressed patients with preexisting left ventricular impairment, ventricular arrhythmias, and/or conduction disease. RESULTS Doxepin (1) did not have a robust effect on heart rate, (2) did not adversely affect left ventricular function, (3) did have a significant antiarrhythmic effect, (4) slowed cardiac conduction, and (5) caused a significant increase in orthostatic hypotension. Five (16%) of the 32 patients dropped out due to cardiovascular side effects. The overall dropout rate was 41%. CONCLUSIONS The cardiovascular effects of doxepin in depressed patients with heart disease are comparable to those documented for imipramine and nortriptyline. Doxepin afforded no greater margin of cardiovascular safety; in fact, the drug was poorly tolerated by this patient population.