Should psychiatrists use atypical antipsychotics to treat nonpsychotic anxiety?

There is neurobiologically based, theoretical support for the use of antipsychotic medications in the treatment of anxiety, and two first-generation neuroleptics are approved by the United States Food and Drug Administration for the treatment of nonpsychotic anxiety. However, neuroleptics are associated with a large side effect burden, which has limited their utility in the treatment of nonpsychotic disorders. Because of their somewhat improved safety profile, atypical antipsychotics are increasingly used for the treatment of nonpsychotic anxiety. The published literature describing the efficacy of atypical antipsychotics in randomized, controlled trials involving patients with anxiety disorders is briefly reviewed, and the safety of atypical antipsychotics in nonpsychotic disorders is discussed. There is moderately strong controlled evidence supporting the use of some atypical antipsychotics, either as adjunctive treatment or monotherapy, in the treatment of nonpsychotic anxiety; however, the side effect burden of some atypical antipsychotics probably outweighs their benefits for most patients with anxiety disorders. The evidence to date does not warrant the use of atypical antipsychotics as first-line monotherapy or as first- or second-line adjunctive therapy in the treatment of anxiety disorders. Rigorous, independently funded, long-term studies are needed to support the off-label use of atypical antipsychotics in the treatment of anxiety disorders. Nevertheless, some patients with highly refractory anxiety disorders may benefit from the judicious and carefully monitored use of adjunctive atypical antipsychotics. A careful risk-benefit assessment must be undertaken by the physician, on a case-by-case basis, with appropriate informed consent.