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Pharmacotherapy of Generalized Anxiety Disorder

Karl Rickels, MD, and Moira Rynn, MD

Published: December 31, 2002

Article Abstract

Less than one third of people afflicted with generalized anxiety disorder (GAD) experience spontaneousremission, and the symptoms of GAD wax and wane throughout a person’s life. The burden ofGAD may be reduced with psychopharmacologic therapy. The medications with the most evidence ofefficacy in GAD are the benzodiazepines, including a new long-acting formulation of alprazolam.These drugs have a low incidence of side effects but may cause physical dependence, withdrawal, andsedation. Antidepressants are also efficacious in GAD but act less quickly than benzodiazepines. Tricyclicantidepressants such as imipramine may substantially reduce symptoms of anxiety but are notconsidered a first-line therapy because of their side effects spectrum. The extended-release formulationof venlafaxine and selective serotonin reuptake inhibitors such as paroxetine and sertraline arealso efficacious in GAD. While their association with sexual dysfunction may be intolerable for someadults, these drugs may be more appropriate than the benzodiazepines because their chronic use doesnot lead to dependence. Buspirone also significantly reduces symptoms of GAD and is associatedwith less sexual dysfunction than SSRIs and less sedation than benzodiazepines. Combining antidepressantand benzodiazepine therapy or medication treatment and psychotherapy may lead to an increasein improvement in patients not responding to 1 treatment approach alone. The most effectivetreatment for managing the recurrent symptoms of this chronic disorder will remain unknown untilmore long-term studies using both drug and nondrug therapies are conducted. Remission rates are stillonly about 40%, signifying the need for improved treatment interventions.

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