Pharmacologic treatments effective in both generalized anxiety disorder and major depressive disorder: clinical and theoretical implications

Objective: To review the efficacy of anxiolytics (alprazolam and azapirones) in major depressive disorder (MDD) and that of antidepressants in generalized anxiety disorder (GAD), thereby exploring the possible theoretical and clinical implications of this efficacy. Method: A Medline literature search was performed for the period January 1980 to September 1997 of randomized, double-blind comparison studies between anxiolytics and antidepressants in the acute treatment of adult patients with either MDD or GAD. Results: Alprazolam, at doses double those generally recommended for anxiety disorders, appears to be as effective as tricyclic antidepressants (TCAs) in the acute treatment of mild to moderate MDD. Alprazolam was also found to have a more rapid onset of action than do TCAs, particularly for the improvement of anxiety, somatization, and insomnia. Two azapirones (buspirone andgepirone) also have demonstrated a modest acute antidepressant effect in preliminary studies, albeit only in a depressed outpatient sample with considerable anxiety at baseline. Finally, various antidepressant drugs (imipramine, trazodone, paroxetine) were shown to have, at the least, comparable efficacy to benzodiazepines (BZDs) in the acute treatment of GAD. Conclusions: The nonspecificity of treatment response suggests that GAD and MDD are 1) different expressions of a similar disorder with a common neurobiological substrate, 2) discrete diagnostic entities that respond to independent pharmacological effects of the same drugs, or 3) a combination of the two (heterogeneity hypothesis). The most relevant clinical finding is the efficacy of antidepressants in the acute treatment of GAD.