Quetiapine augmentation of paroxetine CR for the treatment of refractory generalized anxiety disorder: Preliminary findings

Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Psychopharmacology (Impact Factor: 3.88). 05/2008; 197(4):675-81. DOI: 10.1007/s00213-008-1087-x
Source: PubMed


More data are needed to guide "next step" strategies for patients with generalized anxiety disorder (GAD) remaining symptomatic despite initial pharmacotherapy.
This study prospectively examined the relative efficacy of quetiapine versus placebo augmentation for individuals with GAD remaining symptomatic with initial paroxetine CR pharmacotherapy.
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.
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.
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.

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    • "There have been few studies of the further management of patients with GAD who had not responded to first-line interventions. The findings of small randomized placebo-controlled augmentation studies suggest that augmentation of antidepressants with antipsychotic drugs (olanzapine, quetiapine, and risperidone) may be beneficial,74–76 though the evidence for quetiapine augmentation is inconsistent77 and uncertain for ziprasidone augmentation.78 However, the findings of a recent large randomized placebo-controlled augmentation study demonstrate that the addition of pregabalin to SSRI or SNRI antidepressant drugs is superior to continued treatment with antidepressants alone.71 "
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    ABSTRACT: A PREVIOUS REVIEW SUMMARIZED WHAT WAS THEN KNOWN ABOUT THE POTENTIAL ROLE OF PREGABALIN IN THE TREATMENT OF PATIENTS WITH GENERALIZED ANXIETY DISORDER (GAD): this review provides an update on its pharmacological properties and presumed mechanism of action, the liability for abuse, and efficacy and tolerability in patients with GAD. Pregabalin has a similar molecular structure to the inhibitory neurotransmitter gamma amino butyric acid (GABA) but its mechanism of action does not appear to be mediated through effects on GABA. Instead, its anxiolytic effects may arise through high-affinity binding to the alpha-2-delta sub-unit of the P/Q type voltage-gated calcium channel in "over-excited" presynaptic neurons, thereby reducing the release of excitatory neurotransmitters such as glutamate. The findings of randomized controlled trials and meta-analyses together indicate that pregabalin is efficacious in both acute treatment and relapse prevention in GAD, with some evidence of an early onset of effect, and broad efficacy in reducing the severity of psychological and physical symptoms of anxiety. It also has efficacy as an augmenting agent after non-response to antidepressant treatment in GAD. Continuing vigilance is needed in assessing its potential abuse liability but the tolerability profile of pregabalin may confer some advantages over other pharmacological treatments in the short term for treatment in patients with GAD.
    Full-text · Article · Jun 2013 · Neuropsychiatric Disease and Treatment
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    • "Extended-release quetiapine fumarate (quetiapine XR) offers a potential treatment option for GAD. While an augmentation study with a small sample size (6/11 patients completed) reported no additional benefit when quetiapine was added to paroxetine controlled release (Simon et al. 2008), other studies have reported positive efficacy results for quetiapine as either monotherapy or adjunct therapy in patients with GAD (Adson et al. 2004 ; Galynker et al. 2005 ; Katzman et al. 2008b). This study evaluated the efficacy and tolerability of quetiapine XR as once-daily monotherapy for GAD. "
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    ABSTRACT: The efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR) once-daily monotherapy in generalized anxiety disorder (GAD) was assessed. This multicentre, double-blind, randomized, placebo- and active-controlled, phase III trial consisted of a 1- to 4-wk enrolment/wash-out period and a 10-wk (8-wk active treatment, 2-wk post-treatment drug-discontinuation) study period; 873 patients were randomized to 50 mg or 150 mg quetiapine XR, 20 mg paroxetine, or placebo. Primary endpoint was change from randomization at week 8 in Hamilton Rating Scale for Anxiety (HAMA) total score. At week 8, all active agents produced significant improvements in HAMA total and psychic subscale scores vs. placebo; HAMA somatic subscale scores were significantly reduced only by 150 mg quetiapine XR. Significant separation from placebo (-2.90) in HAMA total score was observed at day 4 for 50 mg quetiapine XR (-4.43, p<0.001) and 150 mg quetiapine XR (-3.86, p<0.05), but not for paroxetine (-2.69). Remission (HAMA total score 7) rates at week 8 were significantly higher for 150 mg quetiapine XR (42.6%, p<0.01) and paroxetine (38.8%, p<0.05) vs. placebo (27.2%). The most common adverse events (AEs) were dry mouth, somnolence, fatigue, dizziness, and headache, for quetiapine XR, and nausea, headache, dizziness for paroxetine. A lower proportion of patients reported sexual dysfunction with quetiapine XR [0.9% (50 mg), 1.8% (150 mg)] than with placebo (2.3%) or paroxetine (7.4%). The incidence of AEs potentially related to extrapyramidal symptoms was: quetiapine XR: 50 mg, 6.8%, 150 mg, 5.0%; placebo, 1.8%; and paroxetine, 8.4%. Once-daily quetiapine XR is an effective and generally well-tolerated treatment for patients with GAD, with symptom improvement seen as early as day 4.
    Full-text · Article · Aug 2009 · The International Journal of Neuropsychopharmacology
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    ABSTRACT: Not Available
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