Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: Evaluate the efficacy and tolerability of quetiapine (QTP) combined with lithium (Li) or divalproex (DVP) in the treatment of acute mania. METHODS: Patients were randomized to 21 days of double-blind treatment with QTP plus Li/DVP, or placebo (PBO) plus Li/DVP. QTP was rapidly dosed up to a maximum of 800 mg/day; Li was dosed to 0.7-1.0 mEq/L; or DVP to 50-100 microg/mL. RESULTS: Fifty-six of 91 (61.5%) individuals in the QTP + Li/DVP group compared with 49 of 100 (49%) taking PBO + Li/DVP completed the study. A significantly greater mean reduction in total Young Mania Rating Scale (YMRS) score was observed at end-point in patients receiving QTP + Li/DVP compared with those in the PBO + Li/DVP group (-13.76 versus -9.93; p = 0.021). The response rate (> or =50% YMRS improvement) was significantly higher in the QTP + Li/DVP group than in PBO + Li/DVP-treated patients (54.3% versus 32.6%; p = 0.005), as was the proportion of patients achieving clinical remission (YMRS < 12) (45.7% versus 25.8%; p = 0.007). Patients receiving QTP + Li/DVP also had a significantly greater improvement in Clinical Global Impressions-Bipolar (CGI-BP) Severity of Illness scores (-1.38 versus -0.78; p = 0.001). The mean last-week dose of QTP was 584 mg/day in patients meeting response criteria. Common adverse events (at least 10% and twice the rate of Li/DVP) in the QTP + Li/DVP group included somnolence, dry mouth, asthenia, and postural hypotension. CONCLUSIONS: Quetiapine combined with either Li or DVP has superior efficacy compared with Li or DVP monotherapy for treating patients with bipolar mania. Combination therapy was well-tolerated and most adverse events were mild, withdrawal because of adverse events being only 5% compared with 6% on Li or DVP monotherapy.

A comparison of the relative safety, efficacy, and tolerability of quetiapine and risperidone in outpatients with schizophrenia and other psychotic disorders: the quetiapine experience with safety and tolerability (QUEST) study.

BACKGROUND: The few published direct comparative studies of the tolerability and efficacy of atypical antipsychotic agents were performed in relatively homogeneous populations that may not be typical of patients seen in clinical practice. OBJECTIVE: The Quetiapine Experience with Safety and Tolerability (QUEST) study compared the relative safety, tolerability, and efficacy of quetiapine and risperidone in outpatients with a broad range of psychotic symptoms. METHODS: This was a multicenter, 4-month, open-label, randomized clinical trial. Patients were randomized in a 3:1 ratio to receive quetiapine or risperidone. Doses were adjusted to maximize efficacy and to minimize adverse events. Extrapyramidal symptoms (EPS) were assessed with an EPS checklist; adverse events were recorded. Efficacy was assessed using the Clinical Global Impression (CGI) scale, Positive and Negative Symptom Scale (PANSS), and Hamilton Rating Scale for Depression (HAM-D). RESULTS: A total of 728 patients were randomized, 553 to quetiapine and 175 to risperidone. Mean prescribed doses over the study period were 253.9 mg/d quetiapine and 4.4 mg/d risperidone. At the end of 4 months, EPS declined in both treatment groups, but quetiapine-treated patients were significantly less likely to require dose adjustment or concurrent anti-EPS medication (P < 0.001). The most common adverse events in the quetiapine and risperidone groups were somnolence (31.3% and 15.4%, respectively), dry mouth (14.5% and 6.9%), and dizziness (12.7% and 6.9%). Overall, tolerance to side effects with the 2 drugs, measured by dropout rates, was comparable. At each visit, a higher percentage of quetiapine-treated patients showed improvement on the CGI scale, but there were no significant between-group differences on the PANSS. At end point, quetiapine-treated patients had significantly lower HAM-D scores (P = 0.028). CONCLUSIONS: The results of this study suggest that quetiapine is as effective as risperidone for the treatment of psychotic symptoms, is more effective for depressive symptoms, may have a more favorable EPS profile, and has comparable overall tolerability.

A randomized, double-blind, placebo-controlled trial of the effect of zafirlukast on upper and lower respiratory responses to cat challenge.

BACKGROUND: Zafirlukast, a leukotriene antagonist, has been shown to have protective effects against a variety of asthma triggers. OBJECTIVE: Our purpose was to evaluate zafirlukast's effects on upper and lower airway responses to cat allergen exposure with use of a well-characterized cat exposure model. METHODS: In a double-blind, placebo-controlled, cross-over trial 18 subjects with cat-induced asthma were randomly assigned to receive 1 week each of zafirlukast or placebo followed by a 1-hour cat challenge. Upper and lower respiratory symptoms were rated and spirometry and acoustic rhinometry were performed. Challenges were stopped early if the subject was too uncomfortable or had a >50% decrease in FEV(1). RESULTS: Overall changes in FEV(1) were significantly different with zafirlukast treatment (P = .02). Significant differences in FEV(1) change were detected at 15 and 30 minutes (P = .027 and .05, respectively) but not at 45 and 60 minutes. Changes in acoustic rhinometry were also significantly different at 15 and 30 minutes (P =.05 and .0005, respectively) but not at 45 and 60 minutes. Challenge length was significantly longer with zafirlukast versus placebo after adjustment for differences in allergen exposure (P = .022). Respiratory symptom scores were significantly different (lower respiratory, P < .001; upper respiratory, P = .038) through the first 30 minutes of the challenge after adjustment for allergen exposure. CONCLUSIONS: Zafirlukast was significantly more effective than placebo in preserving pulmonary function and nasal anatomy and extending challenge length when cat-sensitive asthmatic subjects were exposed to high levels of cat allergen.

Risk factor assessment for the acquisition of fluoroquinolone-resistant isolates of Pseudomonas aeruginosa in a community-based hospital.

A case-control study was performed in a community-based nonteaching hospital to assess patient risk factors for the acquisition of fluoroquinolone-resistant isolates of Pseudomonas aeruginosa. Fifty-five patients who were hospitalized between July 1, 1993 and December 31, 1993 and who had P. aeruginosa recovered from a clinical specimen were included in the analysis. Two patient populations were designated based on the fluoroquinolone susceptibility of their P. aeruginosa isolates. Statistical evaluation using univariate analysis of demographic and clinical data from the 42 patients with quinolone-susceptible P. aeruginosa and the 13 patients with quinolone-resistant P. aeruginosa demonstrated that prior receipt of a fluoroquinolone was the only significant risk factor for the subsequent emergence of fluoroquinolone resistance among P. aeruginosa isolated from patients hospitalized in this small community-based institution (p = 0.0196). Multivariate analysis supported the finding that prior receipt of a fluoroquinolone was the major risk factor for the isolation of fluoroquinolone-resistant P. aeruginosa (p = 0.0004); isolation of this Gram-negative bacillus from sputum (p = 0.0306) and a history of recent surgery (p = 0.0058) were also significantly associated as risk factors for resistance.