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 ≤ 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.
Key Words
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Article Info
Publication History
Published online: September 03, 2005
Accepted:
July 1,
2005
Received in revised form:
June 13,
2005
Received:
November 17,
2004
Identification
Copyright
© 2005 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
