Treating Generalized Anxiety Disorder With Second Generation Antipsychotics

Abstract

Most individuals with generalized anxiety disorder (GAD) fail to achieve remission despite standard treatments. As a result, we examined the efficacy and tolerability of second-generation antipsychotics (SGAs) as (a) augmentation or (b) monotherapy for GAD. We searched MEDLINE, EMBASE, PsycINFO, the Cochrane Library, controlled trials databases, and the abstracts of scientific meetings for all trials of GAD treatment with SGAs in adults. Randomized, double-blind, parallel-group trials examining SGA augmentation and monotherapy were meta-analyzed. Five augmentation studies containing 912 adults with refractory GAD indicated that SGA augmentation was not more likely to produce clinical response or remission than placebo and was associated with an increased risk of all-cause discontinuation (relative risk [RR] = 1.43; 95% confidence interval [CI], 1.04-1.96). There was no difference in the Hamilton Anxiety Rating Scale on change from baseline or weight gain between groups. Four SGA monotherapy studies containing 1383 patients with GAD indicated that treatment with 150 mg of quetiapine was more likely to lead to a clinical response (RR = 1.31; 95% CI, 1.20-1.44), remission (RR = 1.44; 95% CI, 1.23-1.68), and a greater decrease in the Hamilton Anxiety Rating Scale score (-3.66; 95% CI, -5.13 to -2.19) than placebo. However, an increased risk of all-cause discontinuation (RR = 1.30; 95% CI, 1.09-1.54) and weight gain (2.2 lb; 95% CI, 1.16-3.24) was observed. Existing data suggest that SGAs are not superior to placebo as augmentation for refractory GAD. Quetiapine monotherapy is more efficacious than placebo for uncomplicated GAD, but issues with adverse effects and tolerability may limit its use.

Anxiety disorders in older people

“…The role of atypical antipsychotics is less clear; recent systematic reviews of trials involving adults of all ages find some benefit associated with quetiapine in GAD. 127,128 In older patients, however, adverse events associated with use of atypical antipsychotics included increased risk of death, stroke, extrapyramidal symptoms and urinary tract infections.…”

Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders

“…Atypical antipsychotics : Atypical antipsychotics are associated to varying degrees with weight gain, diabetes, and other metabolic side effects, including alterations in glucose and lipid levels [109-116]. Metabolic disturbances generally appear to be higher with olanzapine, intermediate with risperidone and quetiapine, and lower with aripiprazole, asenapine, lurasidone, and ziprasidone [109-114].…”

“…Two meta-analyses [115,116] concluded that quetiapine was significantly superior to placebo and equivalent to antidepressants [115] for the treatment of GAD. However, quetiapine was associated with more weight gain and sedation, and higher dropout rates due to adverse events compared with placebo or antidepressants [115,116]. Due to tolerability and long-term safety concerns with atypical antipsychotics, this treatment is recommended as a second-line option for patients who cannot be provided antidepressants or benzodiazepines.…”

“…Third-line adjunctive therapies: A meta-analysis of five RCTs of adjunctive atypical antipsychotics found no significant improvement in response rates but higher discontinuation rates versus placebo in patients with refractory GAD [116]. …”

Managing the Classification of Psychiatric Diagnoses

“…Our current DSM diagnostic system has greatly complicated diagnosis through an inordinately large number of classes and subclasses of psychiatric diagnoses, with uneven applications at the third and fourth levels. Our system has complicated diagnosis to the point that many generalists have largely abandoned it in their outpatient treatment decisions (Lalonde and VanLieshout, 2011;Mojtabai and Olfson, 2011). Diagnoses without demonstrable clinical utility run the risk of diminishing the DSM to a labeling function at best or a defunct document at worst (Link et al, 1989).…”