Transdermal scopolamine, oral meclizine, and placebo in motion sickness.

The efficacy of transdermal scopolamine, oral meclizine, and placebo in protection against motion sickness was compared in a double-blind crossover study. Thirty-six healthy subjects were exposed to motion three times for 90 min in a ship-motion simulator. Transdermal applications were made and tablets were taken at least 12 and 2 hr before exposure to motion. Transdermal scopolamine provided better protection than placebo or meclizine. Dryness of mouth was the only side effect reported more frequently for one regimen, transdermal scopolamine.

Withdrawal reactions to diazepam in combined imipramine/diazepam treatment of primary nonagitated depressed outpatients.

Twenty-seven outpatients who had primary nonagitated depression that had been treated for 3.5 months with imipramine were included in the study. Of these, 14 patients were given additional diazepam treatment (10 mg/day) and 13 patients got placebo. The additional medication was stopped, and withdrawal reactions were observed after two weeks. The depression scores (both global evaluation and CPRS) increased significantly in the diazepam group, without any changes in the placebo group. Eleven patients in the diazepam group and four in the placebo group reported their condition as impaired after discontinuing their additional medication. Four patients in the placebo group and none in the diazepam group reported improvement. The level of working activity decreased significantly in the diazepam group and increased in the placebo group. The serum level of imipramine decreased in the placebo group (P = 0.07), but not in the diazepam group. Serum levels of desipramine decreased significantly in both groups (P less than 0.05). Our study indicates that the discontinuation of diazepam, even when given in moderate dosage over a relatively short period of time, may cause withdrawal reactions in combined antidepressant/diazepam treatment. This may be caused by a possible tendency for the depression to become chronic. Such chronicity may be the reason for secondary dependency to diazepam.

Treatment of the restless legs syndrome with carbamazepine: a double blind study.

One hundred and seventy four patients suffering from the restless legs syndrome were examined in a double blind, between patient, placebo controlled study in general practice for five weeks to investigate the effects of carbamazepine and placebo on the syndrome. The syndrome was more common among middle aged women with relatively low systolic blood pressure. The median haemoglobin concentration was about average for the population, but the severity of the symptoms seemed to increase with decreasing concentrations of haemoglobin. Both placebo and carbamazepine showed a significant therapeutic effect (p less than 0.01). Carbamazepine was significantly more effective than placebo (p less than or equal to 0.03). The significant therapeutic effect of placebo in restless legs showed that only double blind controlled trials can confirm the efficacy of suggested treatments.

Transdermal scopolamine in drooling.

The effect of oral anticholinergic drugs has been limited in the treatment of drooling. Transdermal scopolamine (1.5 mg/2.5 cm2) offers advantages. One single application is considered to render a stable serum concentration for 3 days. A distinct reduction of basal salivation was demonstrated in an open trial of six healthy volunteers. Eighteen mentally retarded patients with a drooling problem were studied in a double-blind, placebo-controlled cross-over trial. The therapeutic effect of transdermal scopolamine was assessed by a visual analogue scale. Three patients dropped out due to loss of the system. In the remaining 15 patients, the active drug caused a reduction of drooling which was significant in the period from 24 to 72 h. There were few and slight objective signs of unwanted effects. Scopoderm may cause drowsiness and affect tooth health. The management of drooling should primarily be focused on the cause. Sensomotor training is often valuable in cerebral palsy. Factors such as nasal obstruction, mucosal irritation, and drug-induced parkinsonism should be given attention. Sometimes, however, a temporary symptomatic treatment is indicated, for example on special occasions or in order to cure peri-oral skin lesions. Transdermal scopolamine may offer this possibility.

Comparison of the serum levels in primary non-agitated depressed out-patients treated with imipramine in combination with placebo, diazepam or dixyrazine.

Sixty-three non-agitated depressed out-patients were selected according to the Feighner-Robins-Guze criteria for primary depressions for a double-blind, between-patient randomized study for an 8 week duration. All the patients were treated with imipramine following a fixed dose schedule for the first 2 weeks and thereafter according to clinical response (100-200 mg/day). This treatment was combined with either placebo, diazepam (10 mg/day) or dixyrazine (50 mg/day). The serum concentration of imipramine both at 2 weeks and later was significantly higher (P less than 0.05) in the group treated with dixyrazine than in the other two groups. In the group treated with diazepam, the serum levels of imipramine and desipramine were significantly lower than in the placebo group. The serum concentrations of diazepam, desmethyldiazepam and dixyrazine were almost unchanged during the study. No significant correlation was found between the dosage and the serum concentration of imipramine or desipramine. The change in mean CPRS-score correlated neither with the imipramine nor with the desipramine serum levels, it did correlate but negatively with the degree of side effects. The degree of side effects correlated positively with the serum concentration of desipramine.

Iopentol in patients with chronic renal failure: its effects on renal function and its use as glomerular filtration rate parameter.

Iopentol (mean dose 0.42 g I kg-1) was administered for abdominal aortography and pelvic angiography in 10 patients with advanced non-diabetic chronic renal failure (S-creatinine 672 +/- 259 mumol l-1, mean +/- SD). Renal glomerular function measured as creatinine clearance and plasma clearance of [99Tcm]-diethyl-enetriaminepentaacetic acid (DTPA) was unchanged by iopentol, as also was urinary excretion of the renal tubular enzymes N-acetyl-beta-glucosaminidase (NAG) and alkaline phosphatase (ALP). The elimination of iopentol from serum and urine was delayed, and detectable serum and urine concentrations were found 5 days after administration of the contrast medium. Creatine clearance was 47% higher than the corresponding renal iopentol clearance. Plasma iopentol clearance, measured as the total area under the plasma concentration curve, was 40% higher than renal iopentol clearance because of extrarenal elimination of iopentol. We conclude that abdominal aortography with iopentol can be performed without effects on renal glomerular or tubular function parameters in patients with advanced renal failure. If iopentol is used for measurement of glomerular filtration rate (GFR) in this group of patients, one should measure renal clearance, as plasma clearance overestimates GFR.

Pharmacokinetics of iopentol in patients with chronic renal failure.

Iopentol 350 mg I/ml was injected in doses of 265 to 533 mg I/kg b.w. (mean 417 mg I/kg b.w.) in 10 patients with advanced nondiabetic chronic renal failure (S-creatinine 672 +/- 259 mumol/l (mean +/- SD)). Urine (10 patients) and feces (7 patients) were collected at 24 h intervals for 5 days after the injection. The elimination of iopentol was delayed. Five days after injection a mean of 54% (range 35-79%) of the dose was recovered in urine, and 11% (0-20%) in feces. Mean elimination half-life was 28.4 h, about 14 times the half-life found in healthy volunteers. The apparent volume of distribution was 0.27 l/kg b.w., indicating distribution only to extracellular fluid. Using renal iopentol clearance as reference value, GFR was overestimated by 40 to 60% with iopentol total clearance, showing extrarenal elimination of iopentol. The difference was most pronounced in patients with low GFR. In conclusion, this study shows an extrarenal elimination of iopentol and demonstrates a substantial increase in the fecal elimination in patients with severe renal failure.