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Generalized anxiety disorder is characterized by excessive chronic anxiety in association with many somatic symptoms. The disorder has pervasive effects on quality of life, including work, social and educational aspects and requires long-term therapy. Available studies in patients are the Diagnostic and Statistical Manual of Mental Disorders, third edition-revised and fourth edition, which have defined generalized anxiety disorder and demonstrate the efficacy of benzodiazepines, azapirones, some antidepressants and psychotherapy. Benzodiazepines are effective anxiolytics for short-term use but are accompanied by many adverse events. The antidepressants, paroxetine and venlafaxine (Efexor), have demonstrated efficacy in patients with generalized anxiety disorder with mild side-effect profiles. They have the additional benefit of efficacy in depression, which frequently occurs comorbidly in these patients. Long-term efficacy has been shown with venlafaxine in the treatment of this chronic condition, confirming that as in depression, the goal must not just be remission beyond simple symptom resolution but also on to improved functioning and quality of life. Psychotherapy with applied relaxation, cognitive therapy and cognitive behavioral therapy show the most promise in resolving and maintaining treatment gains in the long-term. These approaches may be useful alone or in combination with adjunctive pharmacotherapy to achieve remission. Based on current evidence, the recommended approach to achieving long-term benefits for patients with generalized anxiety disorder is antidepressant therapy with paroxetine or venlafaxine in combination with cognitive behavioral therapy.