Diazepam placebo-controlled studies

Fontaine R, Annable L, Chouinard G, et al. Bromazepam and diazepam in generalized anxiety a placebo-controlled study with measurement of drug plasma concentrations. J Clin Psychopharmacology 1983 3 80-87. 

Another placebo-controlled study tested the effectiveness of ginger in preventing postoperative nausea and vomiting (Arfeen et al., 1995). This randomized, double-blind study included 108 subjects slated for elective gynecologic laparoscopy. The number of subjects provided 80% power to detect a reduction in the incidence of nausea from 30% to 20%. All patients received 10 mg of diazepam orally and were randomized to receive two 500 mg ginger capsules, one 500 mg ginger capsule and one placebo capsule, or two placebo capsules 1 h prior to surgery. Nausea, when present, was rated on a scale of 1 to 3 (mild,... 

In a placebo-controlled study in 12 healthy subjects, intravenous pantoprazole 240 mg for 7 days did not change the half-life, clearance and AUC of a 100-microgram/kg intravenous bolus dose of diazepam."... 

No important changes in the pharmacokinetics of paroxetine were seen when 12 healthy subjects given paroxetine 30 mg daily were also given diazepam 5 mg three times a day. Adverse events were not inereased by the combination. In another study it was foimd that paroxetine did not increase the impairment of a number of psychomotor tests eaused by oxazepam.In vitro studies using human liver mierosomal enzymes have shown that paroxetine is a relatively weak inhibitor of alprazolam metabolism mediated by the cytochrome P450 subfamily CYP3A. Furthermore, a randomised, placebo-controlled study in 22 healthy subjeets reported no evidence for a pharmacokinetic or pharmacological interaction between paroxetine and alprazolam. ... 

In a multicenter, double-blind, placebo-controlled study of the effects of intravenous flumazenil 0.7 mg in reversing the effects of midazolam, 82% of 131 flumazenil-treated patients had complete reversal of sedation, compared with 15% of 65 placebo-treated patients. However, flumazenil reversed midazolam-induced amnesia in only 60% of patients. Dizziness (10%) and nausea (9%) were the most common adverse effects [96 ]. Similar results were obtained in a double-blind, placebo-controlled study in patients who had been given midazolam plus an opioid (fentanyl, pethidine, or morphine) [97 ], intravenous diazepam [98 "], or diazepam plus an opioid [99 ]. 

In a placebo-controlled study in 34 chronic users of diazepam 5—20 mg/day for 5-28 years, a single-dose of flumazenil caused anxiety reactions in nine of 15 subjects with a history of panic attacks, panic attacks were precipitated [126 ]. 

Lodder J, van Raak L, Hilton A, Hardy E, Kessels A. Diazepam to improve acute stroke outcome results of the early gaba-ergic activation study in stroke trial. A randomized double-blind placebo-controlled trial. Cerebrovasc Dis 2006 21 120-127. 

Richelson E, Nelson A Antagonism by neuroleptics of neurotransmitter receptors of normal brain in vitro. Eur J Pharmacol 103 197-204, 1984 Rickels K, Schweizer E The treatment of generalized anxiety disorder in patients with depressive symptomatology. J Clin Psychiatry 54 [suppl) 20-23, 1993 Rickels K, Weisman K, Norstad N, et al Buspirone and diazepam in anxiety a controlled study. J Chn Psychiatry 43(12 pt 2) 81-86, 1982 Rickels K, Feighner JP, Smith WT Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. Arch Gen Psychiatry 42 134-141, 1985 Rickels K, Schweizer E, Weiss S, et al Maintenance drug treatment for panic disorder, 11 short- and long-term outcome after drug taper. Arch Gen Psychiatry 50 61-68, 1993... 

In a randomized, double-blind, placebo-controlled, crossover study in 15 men (mean age 22 years), diazepam 10 mg and clonazepam 1 mg infused over 30 minutes both reduced insulin sensitivity and increased plasma glucose, but the effect of clonazepam was significantly greater (53). 

In a multicenter, double-blind study, 310 patients with generalized anxiety disorder were treated for 6 weeks with abecarnil (mean daily dose 12 mg), diazepam (mean daily dose 22 mg), or placebo in divided doses for 6 weeks (11). Those who had improved at 6 weeks could volunteer to continue double-blind treatment for a total of 24 weeks. Slightly more patients who took diazepam (77%) and placebo (75%) completed the 6-week study than those who took abecarnil (66%). The major adverse events during abecarnil therapy were similar to those of diazepam, namely drowsiness, dizziness, fatigue, and difficulty in coordination. Abecarnil and diazepam both produced statistically significantly more symptom relief than placebo at 1 week, but at 6 weeks only diazepam was superior to placebo. In contrast to diazepam, abecarnil did not cause withdrawal symptoms. The absence of a placebo control makes it difficult to interpret the results of another study of the use of abecarnil and diazepam in alcohol withdrawal, which appeared to show comparable efficacy and adverse effects of the two drugs (12). 

In a double blind, placebo-controlled, crossover study in eight white and seven Chinese men who were extensive metabolizers of debrisoquine and mephenytoin, omeprazole 40 mg/day reduced the oral clearance of diazepam by 38% and increased desmethyldiazepam AUC by 42%. In contrast, in the Chinese men the oral clearance of diazepam fell by only 21% and desmethyldiazepam AUC by 25%. The authors concluded that the extent of the inhibitory effect of omeprazole on diazepam metabolism depends on ethnicity (51). Differences between Caucasians and Asians may account for such effects. 

In a placebo-controlled, randomized, double-blind, three-fold crossover clinical study, 12 healthy volunteers were evaluated for the effects of a single dose of kava extract equivalent to 120 mg kavalactones and 10 mg diazepam. Measurements were taken directly before, and two and six hours post ingestion. The washout period before crossover was seven days. After kava administration, a non-significant increase compared to placebo was noted in the quantitative EEG in the delta/theta intensity in the occipital and frontal areas, as well as a reduction of the alpha-wave relative intensity (P < 0.05). An increase in beta activity typically found with benzodiazepines was not observed with kava. The placebo group witnessed a decline in the relative intensity of the slow delta- and theta-waves and an increase in the alpha-waves (P < 0.001). Maximal effects of diazepam were usually observed two hours after application, as opposed to the kava extract where the effects had not decreased even after six hours. The critical flicker frequency in the psychophysiological tests was found to be lower under the influence of kava extract and diazepam compared to placebo (P < 0.05). In contrast, significant increases in performance in the Pauli Test after the administration of kava extract were noted which were not present with the placebo or diazepam (P < 0.05) (Gessner and Cnota, 1994). 

---