Quetiapine augmentation of paroxetine CR for the treatment of refractory generalized anxiety disorder: preliminary findings.
ABSTRACT 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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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.The International Journal of Neuropsychopharmacology 08/2009; 13(3):305-20. DOI:10.1017/S1461145709990423 · 5.26 Impact Factor
- TENCON '91.1991 IEEE Region 10 International Conference on EC3-Energy, Computer, Communication and Control Systems; 09/1991
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ABSTRACT: Although obsessive-compulsive disorders have been subject to intense multimodal research, their pathogeneses are yet to be fully understood. However, increasing evidence from both preclinical and clinical studies support a role for dopamine in OCD. The studies in this thesis provide circumstantial evidence for the involvement of dopamine in OCD. On the one hand, first exacerbation of OCD symptoms by blocking the dopamine transporter (DAT) with bupropion in OCD patients, and second augmentation of the efficacy of citalopram by blocking the D2 receptor with quetiapine, both confirm dopamine abnormalities in OCD. On the other hand, (1) the absence of abnormal striatal D2 receptor binding at baseline in a [11C]raclopride PET study, (2) no differences in change in BP of [11C]raclopride in the striatum after amphetamine in a [11C]raclopride PET study, together with (3) similar distributions of genotypes or allele frequencies of the COMT or DRD2 receptor between responders and nonresponders to citalopram with quetiapine, challenges the evidence for dopamine alterations in OCD. However, conclusions from our PET and pharmacogenetic study are limited by small sample size. Therefore, enlargement of the sample in future studies is warranted. Heterogeneity of OCD symptoms of participants in our PET study could also be a potential confounder, since various neuroimaging studies suggest that different symptoms may be mediated by distinct neural systems. Taken together, results from this thesis show that patients with OCD who have never been treated before, preferentially benefit from a combination of a SSRI and quetiapine, compared to monotherapy with SSRIs. Immediate augmentation increases the number of responders, though psychiatrists need to consider the increased number of dropouts due to side effects with add-on therapy. Genetic research can provide additional information which patients will respond to a combination of SSRIs and quetiapine.