Treating Generalized Anxiety Disorder
Generalized anxiety disorder (GAD) is a prevalent illness often associated with considerable discomfort and dysfunction. It often co-occurs with bipolar disorder. Traditional treatments of the primary syndrome (occurring in the absence of bipolar disorder) involve serotonin-selective antidepressants and serotonin-noradrenergic reuptake inhibitors such as venlafaxine (Effexor) or duloxitine (Cymbalta). While these are often useful and lead to considerable improvement, they often do not lead to full remission of somatic or accompanying symptoms of insomnia.
Alternative treatment possibilities include the anticonvulsant pregabalin (Lyrica), which has been found effective in four placebo-controlled studies in GAD. A poster presentation by Joshi et al. at the American Psychiatric Association meeting in San Francisco in May 2009 also reported that pregabalin was more effective in reducing sleep disturbance than venlafaxine. Pregabaline is FDA-approved for seizures and fibromyalgia, but not for GAD or pain syndromes. Another treatment possibility is quetiapine (Seroquel), where not only have there been positive efficacy in placebo-controlled studies of patients with GAD, but the patients also experienced improvement in sleep.
Each of the different types of treatments of GAD have had small effect sizes when studied, which suggests that several drugs may need to be used in combination in order to target the various components of generalized anxiety disorder, including persistent and excessive worry, a variety of somatic symptoms, and insomnia.
In the study of Joshi et al., pregabalin was used in the range of 300mg to 600mg/day compared with venlafaxine XR (75mg to 225mg/day) and compared with placebo. Both pregabalin and venlafaxine XR were significantly more effective than placebo for the treatment of GAD. The disturbances that improved on pregabalin included poor sleep adequacy, shortness of breath, and daytime sleepiness.
Micelli also reported on the addition of adjunctive pregabalin after partial response to other treatments for GAD. In this study, patients who were inadequately responsive to a course of an SSRI/SNRI or benzodiazepine after eight weeks were randomized to either pregabalin (150-600 mg/day) or placebo, in addition to continuation of the existing SSRI/SNRI. The change in the Hamilton Anxiety Scale scores (showing a 50% reduction in anxiety) were significantly greater on pregabalin compared with placebo, along with a significantly earlier time to sustained response compared with placebo as well. Common side effects included dizziness, headache, and somnolence, but discontinuations due to side effects were low (4.4%) on pregabalin and non-significantly different from placebo (3.4%).
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