BACKGROUND: There has been little systematic study of "next-step" interventions for patients with generalized anxiety disorder (GAD) who remain symptomatic despite initial pharmacotherapy. We present one of the first randomized controlled trials for refractory GAD, comprising double blind augmentation with olanzapine or placebo for patients remaining symptomatic on fluoxetine. METHODS:Patients remaining symptomatic after 6 weeks offluoxetine (20 mg/day) were randomized to 6 weeks of olanzapine (mean dose 8.7 +/- 7.1 mg/day) or placebo augmentation. RESULTS:Twenty-four of 46 fluoxetine-treated patients were randomized. Olanzapine resulted in a greater proportion of treatment responders based on a Clinical Global Impression-Severity Scale (CGI-S) end point score of 1 or 2 (Fisher's exact test [FET] p < .05) or a 50% reduction in Hamilton Anxiety Scale (HAMA-A) score (FET p < .05). There were no other statistically significant differences for olanzapine compared with placebo augmentation in outcome measures, though rates of remission (HAM-A <or= 7) on olanzapine were higher at the level of a trend (FET, p = .1). Average weight gain for completers was greater with olanzapine than placebo augmentation (11.0 +/- 5.1 vs. -0.7 +/- 2.4 pounds: t = 6.32, p < .001). CONCLUSIONS: Olanzapine may have a salutary effect on anxiety for some GAD patients remaining symptomatic despite initial serotonin selective reuptake inhibitor (SSRI) therapy, but the emergence of significant weight gain represents an important clinical consideration.
RCT Entities:
BACKGROUND: There has been little systematic study of "next-step" interventions for patients with generalized anxiety disorder (GAD) who remain symptomatic despite initial pharmacotherapy. We present one of the first randomized controlled trials for refractory GAD, comprising double blind augmentation with olanzapine or placebo for patients remaining symptomatic on fluoxetine. METHODS:Patients remaining symptomatic after 6 weeks of fluoxetine (20 mg/day) were randomized to 6 weeks of olanzapine (mean dose 8.7 +/- 7.1 mg/day) or placebo augmentation. RESULTS: Twenty-four of 46 fluoxetine-treated patients were randomized. Olanzapine resulted in a greater proportion of treatment responders based on a Clinical Global Impression-Severity Scale (CGI-S) end point score of 1 or 2 (Fisher's exact test [FET] p < .05) or a 50% reduction in Hamilton Anxiety Scale (HAMA-A) score (FET p < .05). There were no other statistically significant differences for olanzapine compared with placebo augmentation in outcome measures, though rates of remission (HAM-A <or= 7) on olanzapine were higher at the level of a trend (FET, p = .1). Average weight gain for completers was greater with olanzapine than placebo augmentation (11.0 +/- 5.1 vs. -0.7 +/- 2.4 pounds: t = 6.32, p < .001). CONCLUSIONS:Olanzapine may have a salutary effect on anxiety for some GAD patients remaining symptomatic despite initial serotonin selective reuptake inhibitor (SSRI) therapy, but the emergence of significant weight gain represents an important clinical consideration.
Authors: Martin A Katzman; Pierre Bleau; Pierre Blier; Pratap Chokka; Kevin Kjernisted; Michael Van Ameringen; Martin M Antony; Stéphane Bouchard; Alain Brunet; Martine Flament; Sophie Grigoriadis; Sandra Mendlowitz; Kieron O'Connor; Kiran Rabheru; Peggy M A Richter; Melisa Robichaud; John R Walker Journal: BMC Psychiatry Date: 2014-07-02 Impact factor: 3.630
Authors: Peter Roy-Byrne; Jason P Veitengruber; Alexander Bystritsky; Mark J Edlund; Greer Sullivan; Michelle G Craske; Stacy Shaw Welch; Raphael Rose; Murray B Stein Journal: J Am Board Fam Med Date: 2009 Mar-Apr Impact factor: 2.657