Dothiepin, a thio analogue of amitriptyline, has been used extensively in Europe during the past 15 years. It is a safe and effective agent for the treatment of major depressive disorder. Although the onset of action is comparable to that of other tricyclic antidepressants, dothiepin may cause fewer intolerable side effects and have less cardiotoxicity than these other compounds. In addition, dothiepin reduces the anxiety associated with some major depressive episodes. These features suggest that dothiepin may be particularly helpful for treating anxious depressed patients and patients who have underlying cardiac disease or who are elderly.