Placebos dosage studies

Gastpar M et al Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression A double-blind, randomized, multicenter, placebo-controlled study. 

In a double-blind, placebo-controlled study, the Bosentan Randomized trial of Endothelin Antagonist Therapy for Pulmonary Arterial I lypertension (BREATHE-2), 33 patients took epoprostenol (2 ng/kg/ min initially, increasing to a mean dosage of 14 ng/kg/min at week 16) and were then randomized for 16 weeks in a 2 1 ratio to bosentan (62.5 mg bd for 4 weeks then 125 mg bd) or placebo (11). There was a non-significant trend towards hemodynamic and clinical improvement with to the combination. There were several early and late major complications (four withdrawals with bosentan + epoprostenol two deaths due to cardiopulmonary failure, one clinical worsening, and one increase in hepatic transaminases and one withdrawal due to increased hepatic transaminases with placebo + epoprostenol. Power was the major limitation of this study, in which only 33 patients were enrolled, and the results should be interpreted with caution. Additional information is needed to evaluate the benefit to harm balance of combined bosentan + epoprostenol therapy in pulmonary arterial hypertension. 

In a double-blind, placebo-controlled study in 74 patients for 2 years, acarbose 100 mg tds, after a stepwise increase in dosage over 5 weeks, improved HbAic (-1.71%) more than placebo (24). Two patients taking acarbose withdrew with drug-related adverse effects. 

Another meta-analysis has been conducted on 19 clinical trials with vitamin E supplementation and follow-up of a duration of more than one year. Nine trials were using vitamin E only without any other supplement and six of them were double-blind/placebo-controlled studies (28), The outcome of the analysis was that high dosages (>400 ILJ/d) may increase all-cause mortality and, therefore, should be avoided. Since in many studies other supplements were used concomitantly to vitamin E the authors concluded, the use of any high-dose supplement should be discouraged until evidence of efficacy is documented from appropriately designed clinical trials. ... 

Lacking the placebo control, the statistician is dependent on outside sources of information to assess the significance of the findings. When validation or qualification of findings is required, previous studies with similar patient populations, drug dosages, study design, and implementation are commonly used to check and interpret the results of studies that do not use a placebo. 

In a double-blind, placebo-controlled study of the addition of low-dose risperidone (mean dosage 2.2 mg/day) to a 5-HT re-uptake inhibitor in refractory obsessive-compulsive disorder in 70 adults, 18 of 20 risperidone-treated patients had at least one adverse effect (37). The adverse effects in both groups included sedation (n = 17 for risperidone, n = 8 for placebo), increased appetite (6 and 3), restlessness (6 and 6), and dry mouth (5 and 5). 

Hurrtirrgtorr Study Group (2003) Dosage effects of riluzole in Huntirrgtorr s disease A multicerrter placebo controlled study. Neurology 61(11) 1551-1556. 

For critical studies, bioequivalency testing should be considered in all cases. All techniques typically require the development of a matching placebo dosage form. Overencapsulation of a bead-filled capsule may necessitate a bead-filled placebo to match the rattling sound of the active product. 

Three double-blind, crossover, randomized, placebo-controUed studies of the role of dextromethorphan in neurological pain conditions in 40 adults with diabetic neuropathy, postherpetic neuralgia, and non-specific neuropathic pain sjmdromes have been reviewed (5). Dextromethorphan dosages varied from 13.5 mg tds on alternate days to 120 mg qds. High-dose dextromethorphan significantly reduced pain in diabetic neuropathy with no effect in postherpetic neuralgia. Sedation (58%) and dizziness (25%) were the most commonly reported adverse effects. 

In a placebo-controUed study in 123 patients with colorectal polyps and normal hearing at frequencies of 250-2000 Hz, efiornithine 0.075-0.4 g/m /day for 12 months had no effect on auditory pure-tone thresholds or distortion product otoacoustic emission (14). There was no hearing loss, in contrast to studies with higher dosages. 

In a double-blind, placebo-controlled study in 28 healthy subjects who were stabilised on warfarin, repaglinide did not alter the anticoagulant effects of warfarin or the steady-state warfarin pharmacokinetics. Therefore, no warfarin dosage adjustment would be anticipated on concurrent use. 

In a placebo-controlled study in 12 healthy subjects, the dosage of heparin given over 4 days did not need modification when clopidogrel 75 mg daily was also given, and the inhibitory effects of clopidogrel on platelet aggregation were unchanged on eoncurrent use. ... 

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