Extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in patients with generalized anxiety disorder and a history of inadequate treatment response: a randomized, double-blind study

Ann Clin Psychiatry. 2013 Nov;25(4):E7-22.


Background: For many patients with generalized anxiety disorder (GAD), first-line treatment does not lead to remission. This study investigated the efficacy and tolerability of adjunctive extended-release quetiapine fumarate (quetiapine XR) in patients with GAD and an inadequate response to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

Methods: Patients were randomized to quetiapine XR or placebo adjunctive to SSRI/SNRIs in an 11-week study. The primary endpoint was change from randomization to week 8 in Hamilton Anxiety Rating Scale (HAM-A) total score. Secondary variables were HAM-A psychic/somatic clusters, response, and remission, and Clinical Global Impression–Severity of Illness (CGI-S) score.

Results: A total of 409 patients received quetiapine XR (n = 209) or placebo (n = 200). The week 8 mean change in HAM-A total score was not statistically significant for quetiapine XR (–10.74; P = .079) vs placebo (–9.61). Secondary variables were generally consistent with the primary analysis, except for a significant reduction in HAM-A total score (week 1) and significant improvements in HAM-A psychic cluster and CGI-S total scores (week 8). Adverse events included dry mouth, somnolence, sedation, headache, and dizziness.

Conclusions: In patients with GAD and an inadequate response to SSRI/ SNRIs, adjunctive quetiapine XR did not show a statistically significant effect for the primary endpoint at week 8, although some secondary endpoints were statistically significant vs placebo. Quetiapine XR was generally well tolerated.

Trial registration: ClinicalTrials.gov NCT00534599.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / pharmacology*
  • Anxiety Disorders / drug therapy*
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / adverse effects
  • Delayed-Action Preparations / pharmacology
  • Dibenzothiazepines / administration & dosage
  • Dibenzothiazepines / adverse effects
  • Dibenzothiazepines / pharmacology*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurotransmitter Uptake Inhibitors / administration & dosage
  • Neurotransmitter Uptake Inhibitors / pharmacology*
  • Norepinephrine / antagonists & inhibitors
  • Psychiatric Status Rating Scales
  • Quetiapine Fumarate
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Treatment Outcome


  • Antipsychotic Agents
  • Delayed-Action Preparations
  • Dibenzothiazepines
  • Neurotransmitter Uptake Inhibitors
  • Serotonin Uptake Inhibitors
  • Quetiapine Fumarate
  • Norepinephrine

Associated data

  • ClinicalTrials.gov/NCT00534599