People with generalised anxiety disorder (GAD) often fail to achieve remission (recovering fully from their disease) despite standard treatments.

This systematic review examines the efficacy and tolerability of second-generation antipsychotics (SGAs) for generalised anxiety disorder as either:

• augmentation therapy, i.e. using it alongside other treatments
• monotherapy, i.e. using it as a stand-alone treatment

The reviewers searched a range of sources for randomised controlled trials (RCT) and found 17 eligible studies in 2,459 individuals, of which 10 were double-blind RCTs and 7 were open label studies without comparators.

Here’s what they found:

• Five augmentation studies containing 912 adults with refractory generalised anxiety disorder indicated that:
• second-generation antipsychotics 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 second-generation antipsychotic monotherapy studies containing 1383 patients with generalised anxiety disorder 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.

The reviewers concluded:

Existing data suggest that second-generation antipsychotics are not superior to placebo as augmentation for refractory generalised anxiety disorder.

Quetiapine monotherapy is more efficacious than placebo for uncomplicated generalised anxiety disorder, but issues with adverse effects and tolerability may limit its use.

LaLonde CD, Van Lieshout RJ. Treating generalized anxiety disorder with second generation antipsychotics: a systematic review and meta-analysis. J Clin Psychopharmacol. 2011 Jun;31(3):326-33. [PubMed abstract]