Information from some 6 to 8 months’ maintenance therapy trials have found continued efficacy over time,14-17 but since GAD is often a long-term and unremitting disorder,18 it needs to be stated that pharmacotherapy, whether with BZs or other drugs, may need to continue for many

years in a significant, number of patients. Results generally show that approximately 70% of patients will respond to adequate BZ treatment (up to 40 mg/day of diazepam or equivalent for at least 3-4 weeks), but less than two thirds will achieve remission of symptoms. In long-term use, tolerance to side effects does occur, but tolerance to the anxiolytic effect of the BZs does not appear.19 Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical With regard to dependence

and withdrawal, compounds with a slower onset, of action, for example, oxazepam, have little reinforcing potential, while those with a long half -life, for example, diazepam and chlordiazepoxide, have a lower propensity to produce withdrawal symptoms, even if stopped abruptly. Inhibitors,research,lifescience,medical Anyway, discontinuation of acute treatment should be slow because of the potential for rebound anxiety and/or clinical relapse, and an adequate pretreatment assessment should be an important step to evaluate whether a subject would be suitable for BZ therapy, including previous history of withdrawal, liability of abuse, or likelihood of poor compliance. For this reason, and because of the high prevalence of comorbid depression, attention has focused also on different medications and antidepressants as potential treatment for GAD (Table Inhibitors,research,lifescience,medical II). Table II. Generalized anxiety disorder (GAD): therapeutic

strategies. BZ, benzodiazepine; SSRI, selective serotonin reuptake inhibitor; TCA, tricylic anti-depressant. Azapirones Ilic first pharmacological treatment for GAD beyond BZs was the azapirone buspirone, a partial 5-hydroxytryptamine (serotonin, 5-HT)-lA (5-HT1A) agonist, which decreases the function of postsynaptic 5-HT2 receptors. It has been demonstrated Inhibitors,research,lifescience,medical to show efficacy in GAD10,20-22 and has been associated with maintenance of efficacy over a I-BET-762 nmr period of several months.15,16 Buspirone is given in two or three divided doses up to 60 mg/day, and its effect is usually not apparent until 2 to 3 weeks into treatment, in contrast to the almost immediate effects aminophylline of BZs. It is not sedating like the BZs; it is not associated with psychomotor impairment, tolerance, dependence, or withdrawal; and it docs not interact with alcohol. The drug works well when there are conspicuous symptoms of worry, apprehensive tension, and irritability,10 and where depressive symptoms are intermixed with anxiety,23 while it is less effective than BZs on somatic and autonomically driven symptoms.