This randomised, double-blind, placebo-controlled study compared the efficacy of venlafaxine XR (75 or 150 mg/d) with diazepam (15 mg/d) over an 8-week treatment period in 540 non-depressed outpatients with generalised anxiety disorder (GAD). At week 8, significant improvements from baseline were observed in the venlafaxine XR, diazepam and placebo groups. Although these improvements were higher in the first two groups than in the placebo group for each of the primary efficacy variables (Hamilton Rating Scale for Anxiety (HAM-A) total, HAM-A psychic anxiety factor, Hospital Anxiety and Depression Scale (HAD) anxiety sub-scale and Clinical Global Impression (CGI) improvement), there were no statistically significant differences between groups. These non-positive results were thought to be due to the very high placebo response observed in some centres. To understand the variability of the study, a secondary preplanned analysis was performed. This involved sub-dividing the study centres according to their ability to detect a two-point mean difference between diazepam and placebo at week 8 on the HAM-A total score. Centres able to show such a difference were termed verum-sensitive. Improvements from baseline to week 8 in venlafaxine XR-treated patients from verum-sensitive centres were significantly greater than in placebo on each of the primary efficacy measures (P ≤ 0.05). This suggests that those centres able to detect an anxiolytic effect of diazepam were also able to detect an anxiolytic effect of venlafaxine XR. Significant differences in baseline demographics, rates of adverse event reporting and rates of patient discontinuations were noted between patients enrolled at verum-sensitive and verum-insensitive sites. These results reflect the importance of study centre selection in accurately determining efficacy in placebo-controlled trials.

The use of benzodiazepines seems to be associated with a deficit in the levels of arousal and attention during vigil. A number of studies have found residual effects a few hours after the intake of these drugs. This paper assesses the effects of a single dose of 10 mg diazepam on self-informed arousal (as evaluated with the Stanford Sleepiness Scale) and sustained attention (as evaluated with the Toulouse Piéron test) the morning after oral intake (11 hours later). Potential differences in the residual effects of benzodiazepines on men and women were also examined. A sample of 42 healthy young university students (21 female, 21 male) was exposed to three counterbalanced experimental conditions (control, placebo, diazepam). Diazepam only caused a reduction in arousal in women, and this deficit was similar to that caused by the intake of a placebo.

Cognitive impairment in long-term high-dose diazepam abusers (dose > 30 mg diazepam/day; duration of abuse > 12 months) was examined by administering four memory-related tests and comparing the outcomes with those of matched controls. Deficits were found in spatial and visual learning, spatial and visual short-term memory (STM) as well as for spatial and visual long-term memory (LTM). As for verbal aspects of memory, solely the acquisition of novel verbal material (verbal learning) was impaired, Furthermore, deficits in a concentration task were observed. In chronic abuse the established memory deficits are similar to cognitive impairment after single doses. Relaxing or anxiety-reducing effects of diazepam were no longer present. The results of this experimental study demonstrate the risks of diazepam use beyond therapeutic range.

Objective: To examine the effects of oral diazepam on blood pressure and anxiety in patients with acute epistaxis.

Study design and setting: A prospective comparative study in an otorhinolaryngology tertiary referral centre.

Participants: Patients with acute epistaxis requiring hospital admission.

Intervention: Oral diazepam.

Main outcome measures: Anxiety and blood pressure levels.

Results: 32 patients received diazepam and 45 did not (control). On average, patients were hypertensive on admission (mean [standard deviation (SD)] systolic blood pressure diazepam group=157 mmHg [26], control=152 mmHg [23]; diastolic blood pressure diazepam group=87 mmHg [16], control=87 mmHg [18]). Both groups showed significant blood pressure reduction on discharge (p<0.0001) but the difference in mean blood pressure reduction between the two groups was insignificant (systolic blood pressure p=0.16, 95% confidence interval [CI]=–5 to +19 mmHg; diastolic blood pressure p=0.43, 95% CI=–8 to +10 mmHg). Anxiety was significantly lower on discharge (p<0.0001) but the difference in mean fall in anxiety scores between the two groups was insignificant (p=0.08, 95% CI=0 to +2). There was no significant correlation between total diazepam and changes in blood pressure (systolic blood pressure p=0.32; diastolic blood pressure p=0.65) or anxiety (p=0.73), nor between blood pressure and anxiety on admission (systolic blood pressure p=0.45; diastolic blood pressure p=0.72).

Conclusions: Elevated blood pressure and anxiety in acute epistaxis patients reduced on epistaxis resolution irrespective of oral diazepam use. The elevated blood pressure does not appear to be directly related to anxiety.

We investigated whether evoked potentials to omitted stimuli could be measured in rats. Such an animal model would provide a measure of aspects of information processing concerned with expectancy and time estimation. In a first experiment, omission evoked potentials (OEPs) were elicited in rats by omitting stimuli (10%) from a train of tone pips with a fixed ISI (3 s). A control session consisted of omitting stimuli (10%) from a train of tone pips with a variable ISI (2.5–3.5 s). In a second experiment, OEPs were measured in rats that received 4 mg·kg−1 diazepam or vehicle sc. In the first experiment, half of the animals showed OEPs that consisted of a late-latency positive wave, the other rats showed a slow negative drift. No OEPs were found in the control session. Rats showing OEPs consisting of a positive wave in Experiment 1 were passed to Experiment 2. In the vehicle condition of the second experiment, all rats showed OEPs. In the diazepam condition no OEPs were found. We found that OEPs can be measured in rats. In addition, OEPs are disrupted by diazepam. We propose that OEPs provide an elegant tool to elicit selectively endogenous EP components.

A 6-months pregnant woman suffering from severe tetanus was successfully treated with intrathecal baclofen. She delivered a premature but healthy neo-nate, and was safely discharged home 40 days after the onset of symptoms of tetanus. Specific aspects of intrathecal baclofen therapy in the pregnant woman are discussed.

The efficacy of anaesthetic premedication has been assessed using sedative scores or a visual analogue scale. However, in both it may be difficult to exclude evaluators’ subjectivity or a placebo effect. Plasma concentration of catecholamines may also be useful for the assessment of patient anxiety. Recently bispectral electro-encephalographic analysis has been developed, and the bispectral index monitor has been reported to give measurements which correlate well with the depth of sedation. In the present study, we have examined the relation between bispectral index values and plasma catecholamine concentrations after oral diazepam premedication. Twenty-eight patients scheduled for elective surgery were randomly assigned to one of two groups: diazepam premedication group (group D(+), n=14) and no premedication group (group D(−), n=14). The patients were premedicated orally with diazepam 10 mg and roxatidine 75 mg in group D(+), and with roxatidine 75 mg only in group D(−) 90 min before arrival in the operating theatre. After patients arrived in the operating theatre, the bispectral index monitor was applied. Venous blood samples(6 mL) were collected in the case of patients in group D(+) for the measurement of plasma catecholamines levels using high-performance liquid chromatography. The bispectral index level (mean±SD) in group D(+): 93.5±773.5 was significantly lower than that in group D(−): 96.1±1.8(P<0.05). There was a significant correlation between bispectral index and plasma norepinephrine levels (r=0.567, P<0.05). The present study suggests that the bispectral index monitor may detect the effect of oral diazepam premedication.

We have investigated the effects of midazolam and diazepam on intracellular calcium (Ca2+) handling in foetal mouse ventricular myocytes using the Ca2+-sensitive fluorescent indicator, indo-1. We also investigated separately whether flumazenil or the L-type Ca2+channel agonist, Bay K8644, antagonized these myocardial depressive effects. Midazolam and diazepam decreased the Ca2+transient and beating rate in a concentration-dependent manner, and these decreases were prevented by Bay K8644. Flumazenil did not antagonize the myocardial depressive effects. In myocytes whose sarcoplasmic reticulum was inhibited by ryanodine, midazolam and diazepam had the same potent cardiodepressive effects. Midazolam and diazepam are direct cardiac depressants, which decrease the Ca2+transient and beating rate, and the L-type Ca2+channel is important in the negative inotropism and chronotropism caused by these drugs.

Irrigation of the bladder after transurethral resection of the prostate is often distressing because of pain arising from detrusor muscle spasm. The effect of post-operative oral diazepam was compared with sacral epidural (caudal) block at the time of surgery, both treatments together and a control group, assessed by three-point rank scoring. Either treatment significantly reduced the incidence of pain reported by patients, P < 0.001. No patient experienced pain after both treatments.