The attempt to develop an efficacious antianxiety agent with no abuse potential resulted in the development of azaperone class of compounds. Currently, Buspirone is the only member of this drug group on the U.S. market. These agents interact with the serotonin system by way of a partial agonist effect at 5-HT_1A receptors. In addition, Buspirone has affinity for dopamine-2 receptors and reduces firing rates in hippocampal-A10 neurons.

Long-term treatment downregulates ßadrenergic-1 adrenoceptors, similar to the effects of antidepressant compounds. Tolerance does not occur to the therapeutic effects.

In general, Buspirone is less sedating than benzodiazepines and does not alter psychomotor functioning. In addition, azaperones are not cross tolerant with the benzodiazepines or other CNS depressants, do not interact with alcohol, and do not have abuse potential. Buspirone is not a controlled substance. Unlike the benzodiazepines, Buspirone does not have anticonvulsant or muscle relaxant properties. Side effects include dizziness, headaches, nausea, nervousness, and paresthesias. Few data are available concerning the use of Buspirone during pregnancy or lactation, and, therefore, use in these situations cannot be recommended.

One potential deficiency in the use of Buspirone for the treatment of anxiety is a 2- to 3-week lag until its therapeutic effects are apparent. Usual doses of Buspirone range between 30 to 60 mg/day, although doses up to 90 mg/day have been used. At doses less than 30 mg/day, Buspirone is no more effective than placebo. Some authors have expressed the opinion that long-term therapy patients discontinue Buspirone treatment more often than they do benzodiazepine therapy; whether this relates to decreased efficacy is uncertain.

Uhde and Tancer reviewed 14 studies of Buspirone in patients with GAD. The studies used DSM-III criteria for diagnosis, which did not include the 6-month duration of symptom requirement of DSM-III-R and DSM-IV. Of the 14 studies, 10 were placebo-controlled and 13 compared Buspirone with a benzodiazepine. One-half of the placebo trials showed Buspirone equivalent to placebo in terms of efficacy. In the nonplacebo comparison studies, Buspirone was comparable with the benzodiazepine. Since the more recent diagnostic criteria are even more rigid than those used in this study, the authors question the efficacy of Buspirone in treating GAD.