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Placebo Phase (placebo + phase)
Selected AbstractsBright light therapy for seasonal affective disorder in Israel (latitude 32.6°N): a single case placebo-controlled studyACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2006L. Moscovici Introduction:, We describe a patient diagnosed as having seasonal affective disorder (SAD, winter depression), an unlikely condition in Israel (latitude 32.6°N), a country with relatively minor daylight photoperiodic changes between seasons. Method:, Case report. Results:, A 46-year-old woman with a clinical picture of depression (Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria for ,major depression with seasonal pattern') reacted positively to 3 weeks of daily bright light therapy of 10 000 lux/wide spectrum. She was asked to wear dark sunglasses during placebo sessions to accommodate an A-B-C single-case-design. The intervention resulted in an improvement of 74,80% in the Hamilton anxiety and depression scales (clinician-rated) and the Beck depression inventory, similar to results obtained in high latitude regions. The depression and anxiety levels returned close to baseline levels following 1 week of the placebo intervention. Conclusion:, Seasonal affective disorder is apparently not limited to certain latitudes. The effect of light therapy was short-lived after discontinuation of the treatment, with rapid relapse occurring in the placebo phase. [source] Treatment of Vasodepressor Carotid Sinus Syndrome with Midodrine: A Randomized, Controlled Pilot StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2005Allan Moore MRCPI Objectives: To evaluate the efficacy of treatment of the vasodepressor form of carotid sinus hypersensitivity (carotid sinus syndrome (CSS)) with midodrine. Design: A prospective, double-blind, randomized, controlled trial of crossover design. Setting: A dedicated outpatient facility with access to tilt-table, digital arterial photoplethysmography, and 24-hour ambulatory blood pressure (BP) monitoring equipment. Participants: Ten older adults (4 male, 6 female, mean age 75, range 66,86 years) with a history of unexplained syncope who displayed an asymptomatic decrease in systolic BP (SBP) of more than 50 mmHg or a symptomatic decrease of more than 30 mmHg within 30 seconds of carotid sinus massage (CSM). Measurements: Symptom reproduction and BP and heart rate changes were evaluated after CSM in supine and semierect positions on the right and then left sides. These measurements were performed on the final day of placebo and active-treatment phases. Ambulatory 24-hour BP monitoring took place on the penultimate and final days of each treatment phase. Results: Eight patients were symptomatic after their initial CSM. The mean±standard deviation SBP decrease after initial CSM was 54±22 mmHg. Initial mean 24-hour ambulatory BP was 127/70±7/5 mmHg. Eight patients reported symptoms after CSM at the end of the placebo phase. The mean SBP decrease at the end of the placebo phase was 49±12 mmHg. The mean 24-hour ambulatory BP was 127/69±9/7 mmHg. One patient reported symptoms after CSM at the end of the active-treatment phase. The mean SBP decrease at the end of the active-treatment phase was 36±9 mmHg. The mean 24-hour ambulatory BP at the end of the treatment phase was 133/75±7/6 mmHg. The differences in symptom reporting and mean SBP decrease after CSM were both significant (P<.01 and P=.03, respectively). Conclusion: The results of this pilot study suggest that treatment of vasodepressor CSS with midodrine significantly reduced the rate of symptom reporting and attenuated SBP decreases after CSM but increased mean 24-hour ambulatory BP. [source] Investigation of the antihypertensive effect of oral crude stevioside in patients with mild essential hypertensionPHYTOTHERAPY RESEARCH, Issue 9 2006Letícia A. F. Ferri Abstract The antihypertensive effect of crude stevioside obtained from the leaves of Stevia rebaudiana (Bertoni) Bertoni (Compositae) on previously untreated mild hypertensive patients was examined. Patients with essential hypertension were submitted to a placebo phase for 4 weeks. The volunteers selected in this phase were randomly assigned to receive either capsules containing placebo during 24 weeks or crude stevioside 3.75 mg/kg/day (7 weeks), 7.5 mg/kg/day (11 weeks) and 15.0 mg/kg/day (6 weeks). All capsules were prescribed twice a daily (b.i.d.), i.e. before lunch and before dinner. After the placebo phase and after each dose of crude stevioside, body mass index, electrocardiogram and laboratory tests were performed. During the investigation blood pressure (BP) was measured biweekly and the remaining data were collected at the end of each stevioside dose step. All adverse events were prospectively recorded but no major adverse clinical effects were observed during the trial. Systolic and diastolic BP decreased (p < 0.05) during the treatment with crude stevioside, but a similar effect was observed in the placebo group. Therefore, crude stevioside up to 15.0 mg/kg/day did not show an antihypertensive effect. Moreover, the results suggest that oral crude stevioside is safe and supports the well-established tolerability during long term use as a sweetener in Brazil. Copyright © 2006 John Wiley & Sons, Ltd. [source] Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 aloneBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2010Juha Grönlund WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Oxycodone is an opioid analgesic that is metabolized mainly in the liver by cytochrome P450 (CYP) 2D6 and 3A4 enzymes. , So far, the effects of CYP2D6 or CYP3A4 inhibitors on the pharmacokinetics of oxycodone in humans have not been systematically studied. WHAT THIS STUDY ADDS , Drug interactions arising from CYP2D6 inhibition most likely have minor clinical importance for oral oxycodone. , When both of CYP2D6 and CYP3A4 pathways are inhibited, the exposure to oral oxycodone is increased substantially. AIM The aim of this study was to find out whether the inhibition of cytochrome P450 2D6 (CYP2D6) with paroxetine or concomitant inhibition of CYP2D6 and CYP3A4 with paroxetine and itraconazole, altered the pharmacokinetics and pharmacological response of orally administered oxycodone. METHODS A randomized placebo-controlled cross-over study design with three phases was used. Eleven healthy subjects ingested 10 mg of oral immediate release oxycodone on the fourth day of pre-treatment with either placebo, paroxetine (20 mg once daily) or paroxetine (20 mg once daily) and itraconazole (200 mg once daily) for 5 days. The plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 h, and pharmacological (analgesic and behavioural) effects were evaluated. RESULTS Paroxetine alone reduced the area under concentration,time curve (AUC(0,0,48 h)) of the CYP2D6 dependent metabolite oxymorphone by 44% (P < 0.05), but had no significant effects on the plasma concentrations of oxycodone or its pharmacological effects when compared with the placebo phase. When both oxidative pathways of the metabolism of oxycodone were inhibited with paroxetine and itraconazole, the mean AUC(0,,) of oxycodone increased by 2.9-fold (P < 0.001), and its Cmax by 1.8-fold (P < 0.001). Visual analogue scores for subjective drug effects, drowsiness and deterioration of performance were slightly increased (P < 0.05) after paroxetine + itraconazole pre-treatment when compared with placebo. CONCLUSIONS Drug interactions arising from CYP2D6 inhibition most likely have minor clinical importance for oral oxycodone if the function of the CYP3A4 pathway is normal. When both CYP2D6 and CYP3A4 pathways are inhibited, the exposure to oral oxycodone is increased substantially. [source] Effect of multiple doses of montelukast on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in humansBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2007Kyoung-Ah Kim Aims To investigate the effect of multiple dosing with montelukast, a selective leukotriene-receptor antagonist, on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in humans. Methods A two-period, randomized crossover study was conducted in 10 healthy subjects. After administration of oral doses of placebo or 10 mg montelukast daily for 6 days, 4 mg rosiglitazone was administered and plasma samples were obtained for 24 h and analyzed for rosiglitazone and N-desmethylrosiglitazone using high-performance liquid chromatography with fluorescence detection. Results During the montelukast phase, the total area under the time-concentration curve (AUC) and peak plasma concentration of rosiglitazone were 102% (90% CI 98, 107%) and 98% (90% CI 92, 103%) of the corresponding values during the placebo phase, respectively. Multiple dosing with montelukast did not affect the oral clearance of rosiglitazone significantly (90% CI 94, 105%; P = 0.50). The AUC ratio and plasma concentration ratios of N-desmethylrosiglitazone : rosiglitazone were not changed by multiple dosing with montelukast (90% CI 90, 103%; P = 0.14). Conclusions Multiple doses of montelukast do not inhibit CYP2C8-mediated rosiglitazone metabolism in vivo despite in vitro findings indicating that montelukast is a selective CYP2C8 inhibitor. [source] Effect of an oral contraceptive preparation containing ethinylestradiol and gestodene on CYP3A4 activity as measured by midazolam 1,-hydroxylationBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2000Sanna Palovaara Aims,To characterize the effect of an oral contraceptive (OC) containing ethinylestradiol and gestodene on the activity of CYP3A4 in vivo as measured by the 1,-hydroxylation of midazolam. Methods,In this randomised, double-blind, cross-over trial nine healthy female subjects received either a combined OC (30 µg ethinylestradiol and 75 µg gestodene) or placebo once daily for 10 days. On day 10, a single 7.5 mg dose of midazolam was given orally. Plasma concentrations of midazolam and 1,-hydroxymidazolam were determined up to 24 h and the effects of midazolam were measured with three psychomotor tests up to 8 h. Results,The combined OC increased the mean AUC of midazolam by 21% (95% CI 2% to 40%; P = 0.03) and decreased that of 1,-hydroxymidazolam by 25% (95% CI 10% to 41%; P = 0.01), compared with placebo. The metabolic ratio (AUC of 1,-hydroxymidazolam/AUC of midazolam) was 36% smaller (95% CI 19% to 53%; P = 0.01) in the OC phase than in the placebo phase. There were no significant differences in the Cmax, tmax, t˝ or effects of midazolam between the phases. Conclusions,A combined OC preparation caused a modest reduction in the activity of CYP3A4, as measured by the 1,-hydroxylation of midazolam, and slightly increased the AUC of oral midazolam. This study suggests that, at the doses used, ethinylestradiol and gestodene have a relatively small effect on CYP3A4 activity in vivo. [source] | ||||||||||