Antidepressant-anxiolytic interactions: involvement of the benzodiazepine-GABA and serotonin systems

1. Recent studies have demonstrated that antidepressant drugs are actually more effective than BZ's in the treatment of anxiety states. The role of two major neurochemical substrates that may be implicated in the anxiolytic activity of antidepressants, the benzodiazepine (BZ)-GABA receptor chloride ionophore complex and central serotonergic pathways, are focused on in this review. 2. A wide range of antidepressants elicit a reduction in BZ receptors and display anxiolytic effects within a conflict paradigm. 3. The anxiolytic activity of antidepressants, however, does not appear to be mediated via the BZ receptor, but possibly via another component of the complex such as the chloride channel-associated with the GABAA receptor. 4. Additionally, as possible candidates for the mechanism of anxiolytic activity of these compounds, results of pharmacological, behavioral and clinical studies point to the importance of serotonin (5-HT)1A receptors and 5-HT transporter sites as targets for the action of antidepressants, triazolobenzodiazepines and anxioselective piperazine derivatives.