Quetiapine augmentation of paroxetine CR for the treatment of refractory generalized anxiety disorder: preliminary findings.
BACKGROUND
More data are needed to guide "next step" strategies for patients with generalized anxiety disorder (GAD) remaining symptomatic despite initial pharmacotherapy.


OBJECTIVE
This study prospectively examined the relative efficacy of quetiapine versus placebo augmentation for individuals with GAD remaining symptomatic with initial paroxetine CR pharmacotherapy.


METHODS
Adult outpatients with GAD were recruited from 2004 to 2007 at two academic centers. Phase 1 consisted of 10 weeks of open-label paroxetine CR flexibly dosed to a maximum of 62.5 mg/day. Those remaining symptomatic (Hamilton Anxiety Scale [HAM-A] >or= 7) at week 10 were randomized to quetiapine or placebo augmentation flexibly dosed from 25 to 400 mg/day.


RESULTS
For participants receiving paroxetine CR (n = 50), there was a significant reduction in HAM-A scores (baseline mean +/- SD = 22.4 +/- 4.2 to endpoint mean +/- SD = 11.2 +/- 6.9; paired t = 12.1, df = 49, t < 0.0001) with 40% (n = 20) achieving remission. Counter to our hypothesis, we did not find significant benefit for quetiapine augmentation of continued paroxetine CR (HAM-A reduction mean +/- SD = 2.6 +/- 5.8 points quetiapine, 0.3 +/- 5.5 points placebo; t = 0.98, df = 20, p = n.s.) in the randomized sample (n = 22) with relatively minimal additional improvement overall in phase 2.


CONCLUSIONS
Although conclusions are considered preliminary based on the relatively small sample size, our data do not support the addition of quetiapine to continued paroxetine CR for individuals with GAD who remain symptomatic after 10 weeks of prospective antidepressant pharmacotherapy and suggest that further research examining strategies for GAD refractory to antidepressants is needed.
Simon
Naomi M
NM
Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. nsimon@partners.org
Connor
Kathryn M
KM
LeBeau
Richard T
RT
Hoge
Elizabeth A
EA
Worthington
John J
JJ
Zhang
Wei
W
Davidson
Jonathan R T
JR
Pollack
Mark H
MH
D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage* / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001008:Anxiety Disorders / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D003987:Dibenzothiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000008:administration & dosage* / Q000009:adverse effects; D010555:Personality Inventory; D011446:Prospective Studies; D000069348:Quetiapine Fumarate
D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D017374:Paroxetine