Flávio Kapczinski, Juliano JSS dos Santos Souza, Angelo ABC Batista Miralha da Cunha, Ricardo RS Schmitt

Pharmacological treatments have been successfully used to treat Generalized Anxiety Disorder (GAD). Benzodiazepine and non benzodiazepine anxiolytics used to be the mainstay for the pharmacological treatment of GAD. However, data emerging over the last two decades have shown that antidepressants may be as effective as anxiolytics in this condition. The use of antidepressants may also be beneficial , because GAD often coexists with major depressive disorder (62% comorbidity) and dysthymia (37%). To assess the efficacy and acceptability of antidepressants for treating generalized anxiety disorder. Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register - CCDANCTR (up to May 2002), Anxiety Neurosis (up to May 2002) and Cochrane Controlled Trials Register (CENTRAL/CCTR) (up to May 2002), MEDLINE (1966 to May 2002), LILACS (1982 to May 2002); reference searching; personal communication; conference abstracts and book chapters on the treatment of generalized anxiety disorder. Randomized controlled trials were included. Non randomized studies and those that included patients with both GAD and another Axis I co-morbidity were excluded. The data from studies were extracted independently by two reviewers. Relative risks, weighted mean difference and number needed to treat were estimated. People who died or dropped out were regarded as having had no improvement. Antidepressants (imipramine, venlafaxine and paroxetine) were found to be superior to placebo in treating GAD. The calculated NNT for antidepressants in GAD is 5.15. Dropout rates did not differ between antidepressants. Only one study presented data on imipramine and trazodone. Imipramine was chosen as the reference drug and, therefore, data on trazodone could not be included in the meta analysis. Only one study was conducted among children and adolescents (Rynn 2000). This showed very promising results of sertraline in children and adolescents with GAD, which warrants replication in larger samples. The available evidence suggests that antidepressants are superior to placebo in treating GAD. There is evidence from one trial suggesting that paroxetine and imipramine have a similar efficacy and tolerability. There is also evidence from placebo-controlled trials suggesting that these drugs are well tolerated by GAD patients. Further trials of antidepressants for GAD will help to demonstrate which antidepressants should be used for which patients.