Drug Development for Anxiety Disorders: New Roles for Atypical Antipsychotics

Anxiety disorders are prevalent and frequently comorbid with depression. Rates of response and remission for anxiety disorders are low despite marked improvements in treatment in the past several decades. Antidepressants and anxiolytics remain the most frequently prescribed agents for anxiety disorders, but the numbers of prescriptions for novel forms of therapy, such as anticonvulsants and atypical antipsychotics are increasing. For the atypical antipsychotics, agonist activity at the 5-HT1A receptor has been hypothesized to translate into anxiolytic effects. A small, but growing, literature suggests that atypical antipsychotics are useful as augmentation therapy for treatment of refractory anxiety disorders. The next generation antipsychotic, aripiprazole, has a unique mechanism of action (ie, combined D2 and 5-HT1A partial agonist and 5-HT2A antagonist) and improves depressive and depressive/anxiety symptoms in patients with schizophrenia. Further studies examining the effect of aripiprazole and other atypical antipsychotic drugs on depressive and anxiety symptoms in patients with refractory anxiety disorders are warranted.