WCA Recommendations for the Long-Term Treatment of Generalized Anxiety Disorder

Abstract

What are the current recommendations for the long-term treatment of generalized anxiety disorder (GAD)? GAD is a common disorder with a lifetime prevalence of 4% to 7% in the general population. GAD is characterized by excessive, uncontrollable worry or anxiety about a number of events or activities that the individual experiences on more days than not over a 6-month period. Onset of GAD symptoms usually occurs during an individual's early twenties; however, high rates of GAD have also been seen in children and adolescents. The clinical course of GAD is often chronic, with 40% of patients reporting illness lasting >5 years. GAD is associated with pronounced functional impairment, resulting in decreased vocational function and reduced quality of life. Patients with GAD tend to be high users of outpatient medical care, which contributes significantly to healtcare costs. Currently, benzodiazepines and buspirone are prescribed frequently to treat GAD. Although both show efficacy in acute treatment trials, few long-term studies have been perform Benzodiazepines are not recommended for long-term treatment of GAD, due to associated development of tolerance, psychomotor impairment, cognitive and memory changes, physical dependence, and a withdrawal reaction on discontinuation. The antidepressant venlafaxine extended-release (XR) has received approval for the treatment of GAD in the United States and many other countries. Venlafaxine XR has demonstrated efficacy over placebo in two randomized treatment trials of 6 months' duration as well as in other acute trials. Paroxetine is the first of the selective serotonin reuptake inhibitors (SSRIs) to receive US approval for the treatment of GAD. Paroxetine demonstrated superiority to placebo in short-term trials, and investigations into the use of other SSRIs are ongoing. This suggests that other SSRIs, and serotonin and noradrenaline reuptake inhibitors, are likely to be effective in the treatment of GAD. Of the psychological therapies, cognitive-behavioral therapy (CBT) shows the greatest benefit in treating GAD patients. Treatment gains after a 12-week course of CBT may be maintained for up to 1 year. Currently, no guidelines exist for the long-term treatment of GAD.

The role of the dynorphin/κ opioid receptor system in anxiety

“…The most widely used therapeutic agents for the treatment of anxiety disorders include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, benzodiazepine anxiolytic and NMDA receptor modulators [5] . However, currently available anxiety disorder modulators are inadequate for patients because of the existence of "nonresponders" or unwanted side effects, such as ataxia, drowsiness, and impairment of cognition [6][7][8] . Increasing evidence indicates that the dynorphin/κ opioid receptor system plays an important role in the regulation of anxiety disorders.…”

O que nossos pacientes querem e necessitam saber sobre transtorno de ansiedade generalizada?

“…26 Furthermore, there is no data that indicate an accumulation of adverse events; e.g. getting Alzheimer or cancer.…”

Targeting the Modulation of Neural Circuitry for the Treatment of Anxiety Disorders

“…Although not as widely prescribed as in the past, these compounds nevertheless remain an effective alternative to SSRIs. That said, the nonselective BZDs are not devoid of side effects, which can include drowsiness, ataxia, impairment of cognition, as well as the risk of dependence and withdrawal symptoms, including increased anxiety, tremors, and seizures (Noyes et al, 1988;Bennett et al, 1998;Yamawaki, 1999;Allgulander et al, 2003). The identification of subtype-selective GABA receptor-positive allosteric modulators, such as zolpidem, which have proven to be effective in the treatment of patients with insomnia while producing fewer untoward side effects than nonselective BZDs, suggested that similar drugs could be developed for anxiety disorders.…”