Selective serotonin reuptake inhibitors (SSRIs) and serotonine reuptake Inhibitors (SNRIs) together with pregabalin are actually considered by international guidelines as the first-line choice for generalized anxiety disorder (GAD) treatment. However, 50% of GAD patients have poor response to first-line treatments and different molecules, such as atypical antipsychotics and mood stabilizers, have been used for treating this condition. Purpose of the present article is to provide an overview of the most recent pharmacological approaches for the treatment of GAD and the rationale for their use.

A research in the main database sources has been conducted to obtain an overview of the new pharmacological approaches in GAD (anticonvulsants, atypical antipsychotics, agomelatine, memantine, ondansetron and riluzole).

Among unlabelled molecules, quetiapine seems to have the most robust evidence of efficacy in GAD. Valproic acid and agomelatine appear to be effective in GAD patients, but the data are preliminary and need to be confirmed by future studies. Quetiapine is a promising molecule for GAD treatment but its use would be complicated by long-term metabolic side effects. Future research will have the objective to find more targeted molecules for the treatment of this disorder in light of its specific etiology.