Drug treatment of panic disorder: the comparative efficacy of imipramine, alprazolam, and trazodone.

Data from 74 patients with panic disorder were evaluated to determine the comparative efficacy of imipramine, alprazolam, and trazodone. All patients were treated with placebo for 3 weeks and were then blindly switched to active treatment for 8 weeks. Both imipramine and alprazolam were highly effective in reducing the symptoms of generalized anxiety, the frequency of panic attacks, and phobic avoidance. However, the time course of these effects differed; alprazolam demonstrated therapeutic properties during the first week, whereas the therapeutic efficacy of imipramine was not clearly apparent until the fourth week of treatment. Relative to imipramine and alprazolam, trazodone was not an effective treatment for panic disorder and was poorly tolerated; only 17 trazodone-treated patients completed at least 4 weeks of treatment, and only 2 patients were considered good or complete responders. These findings support the hypotheses that drugs that are efficacious in the treatment of panic disorders act by altering noradrenergic function and that drugs with primary actions on serotonin function are likely to be less effective treatments. The different time courses of therapeutic action of imipramine and alprazolam indicate that these drugs ameliorate panic anxiety via different mechanisms. The possible therapeutic applications of this observation are discussed.