Introduction: Generalized anxiety disorder (GAD) is a prevalent and very disabling
anxiety disorder. First-line medications are antidepressants such as selective serotonin reuptake
inhibitors (SSRIs) and selective serotonin and noradrenalin reuptake inhibitors (SNRIs). However,
a substantial number of patients do not reach remission while on antidepressants and they
may develop troublesome side effects, which highlights the necessity of new therapeutic options for
Methods: The purpose of this review is to discuss all non-antidepressant treatments studied in GAD.
We searched MedLine for English articles published between 1980 and 2012, containing the following keywords:
“generalized (or generalised) anxiety disorder” OR “anxiety disorder”, AND “drug therapy” OR “herbal medicine”. 76
articles were finally selected.
Results: Pregabalin is the anticonvulsant with the most robust level of evidence in GAD. It rapidly reduces anxiety, has a
safe side effect profile and presents a low potential for abuse. Among antipsychotics, quetiapine is the one of choice in
GAD, with similar efficacy to SSRIs in low dosages, yet with lower overall tolerability. Benzodiazepines, buspirone and
hydroxyzine are Food and Drugs administration (FDA) approved for GAD and have relatively good evidence of efficacy.
Other drugs (betablockers, zolpidem, riluzole, etc.) and natural remedies (e.g. Piper methysticum) could be potential
treatment options, yet additional research is warranted.
Conclusion: Pregabalin and quetiapine are the two most promising non-antidepressant treatments for GAD.