Treatment of generalized anxiety disorder: a comprehensive review of the literature for psychopharmacologic alternatives to newer antidepressants and benzodiazepines.

Objective: Generalized anxiety disorder (GAD) is common, chronic, and debilitating. Treatment with benzodiazepines and newer antidepressants is often inadequate. This article reviews the effectiveness of alternative and augmenting medications, such as older antidepressants, antipsychotics, anticonvulsants, and β-blockers.

Data Sources: A search using MEDLINE (1980 to week 4 of May 2010) with the key words generalized anxiety disorder or GAD and therapeutics or treatment was conducted. Articles included adult patients with a GAD diagnosis that established chronicity of illness. These included a small number of studies that used DSM-III criteria but added a chronicity of symptoms and included all studies that used DSM-III-R and DSM-IV criteria. Articles that did not include medications or that exclusively focused on newer antidepressants (selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, bupropion, and mirtazapine), buspirone, benzodiazepines, or herbal or investigational medications were excluded. Review articles and non-English-language articles were also excluded.

Results: Thirty-six studies were reviewed. All of the references were then analyzed, and key portions were extracted. Many studies were open trials. Double-blind, placebo-controlled studies with imipramine, risperidone, olanzapine, hydroxyzine, ondansetron, tiagabine, valproate, and pregabalin had been conducted. Imipramine, hydroxyzine, valproate, and pregabalin were the most effective, although risperidone, olanzapine, ziprasidone, and aripiprazole may also reduce symptoms.

Conclusions: Several medication strategies can be considered as promising alternatives or augmenting to antidepressant or benzodiazepine therapy in GAD.