Tricyclic antidepressants

Abstract

In the middle 1950s, when imipramine, the first tricyclic antidepressant (TCA), became available, investigators did not consider that this compound might be useful in the treatment of anxiety disorders. Meprobamate and the first benzodiazepines were effective in alleviating anxiety, while imipramine given in a single dose often accentuated tension and agitation. During the later part of that decade Klein and Fink [1] observed that inpatients with “episodic anxiety,” characterized by “the sudden onset of inexplicable panic attacks, accompanied by rapid breathing, palpitations, weakness, and a feeling of impending death” improved on imipramine while other sedatives and phenothiazines were ineffective. This observations led to controlled studies and to the separation of anxiety neurosis into panic disorder and generalized anxiety disorder. Imipramine was found effective in the prevention of panic attacks but not of anticipatory anxiety [2]. Subsequently, several TCAs were developed of which amitriptyline and doxepine had sedative effects. Sedative TCAs became useful in the treatment of anxious and agitated patients with depression, however, the long-term reduction of anxiety was attributed to improvement of depression, rather than to specific anxiolytic effects of TCAs. The effectiveness of imipramine and other TCAs in treatment of panic disorder led to studies of other conditions that have episodic attacks of anxiety, such as simple phobias, social phobia, post-traumatic stress disorder, and obsessive compulsive disorder.