[Pharmacological treatment of generalized anxiety disorders: rationale and limitations]

The rational use of pharmacological treatment in generalized anxiety disorders is still a matter of debate due to the uncertainties concerning the nature, diagnostic criteria and target-symptoms of this frequent and potentially invalidating disorder. If benzodiazepines may still be prescribed for a limited amount of time (i.e. 6 to 12 weeks) due to the fluctuating nature of generalized anxiety, the chronic evolution of this disorder in most patients often justifies the long-term prescription of serotoninergic (5-HT) or dual-action (5HT-NA) antidepressants and sometimes of 5HT-la partial agonists like buspirone. Imipramine, a tricyclic antidepressant was the first to demonstrate its efficacy in carefully selected patients; however, due to the side-effects of this molecule recent guidelines based on controlled clinical trials, suggest to use either serotonergic antidepressants (SSRIs) or venlafaxine as a first-line treatment of generalized anxiety disorders. Because of its pharmacological profile buspirone remains however a useful option in patients with cognitive or addictive problems, especially alcoholics. If most SSRIs have demonstrated efficacy over placebo, head to head comparisons remain limited except for escitalopram which appear better tolerated than paroxétine in this indication. More recently, an anticonvulsant, pregabaline also demonstrated its efficacy in several clinical trials but the symptomatic profile of generalized anxiety patients likely to respond to this GABA analog compared to other psychotropic treatments remain to be established. The traditional use of other psychotropic agents such as hydroxyzine, an H1 histaminergic receptor antagonist, is only supported by limited scientific data; this is also the case of sedative typical antipsychotics which benefit/risk ratio should be carefully evaluated before being prescribed to generalized anxiety patients resistant to other psychotropic agents. However, the possible use of atypical antipsychotics with a better tolerance profile than the typical ones in this indication is presently under investigation in several countries. At last it is important to realize that most clinical trials in this field only include patients with non-comorbid generalized anxiety and that their conclusion may not always be generalizable to most psychiatric patients who are usually characterized by a high rate of comorbidity. In this population the indication of specific pharmacological treatments should rely on a careful evaluation of the patients drug treatment history, of the duration, evolution and functional consequences of their symptoms and of the nature of their possible comorbidity. The treatment of resistant generalized anxiety disorders remains a question for future research but the use of imipramine or sedative antipsychotics could be an option when other treatments have failed to induce any improvement.