Rolipram in major depressive disorder: results of a double-blind comparative study with imipramine.

Rolipram improves signal transmission in central noradrenergic neurones at a pre- and postsynaptic level, and is thus a novel approach in antidepressant therapy. In order to prove efficacy, tolerance, and safety, several controlled studies are underway. Results of a randomized double-blind comparative trial versus imipramine involving 64 in-patients with Major Depressive Disorder (DSM III) in six independent centers will be presented and discussed. The chosen biometric model provided evidence that towards the end of the study imipramine was superior to Rolipram. The particular clinical relevance of this difference is discussed. As regards tolerance, nausea emerged as the typical side-effect of Rolipram, whereas imipramine precipitated mainly anticholinergic side-effects.

Rolipram versus imipramine in inpatients with major, "minor" or atypical depressive disorder: a double-blind double-dummy study aimed at testing a novel therapeutic approach.

Unlike conventional antidepressants, rolipram stimulates both the presynaptic as well as the postsynaptic component of monoaminergic transmission. Several double-blind comparative trials are on the way to assess the clinical efficacy and safety of this novel compound. The present study was a randomized double-blind double-dummy comparison with imipramine in inpatients with major, "minor" and atypical depressions (DSM III). Results show no relevant differences between rolipram and imipramine regarding efficacy and safety.

Is phosphodiesterase inhibition a new mechanism of antidepressant action? A double blind double-dummy study between rolipram and desipramine in hospitalized major and/or endogenous depressives.

Unlike conventional antidepressants, rolipram (a new approach in the treatment of depression) stimulates both the presynaptic and the postsynaptic component of monoaminergic transmission. Several double blind trials are under way to assess the clinical efficacy and safety of this compound. The present study was a randomized, 4-week interindividual double blind double-dummy comparison with desipramine in inpatients with major (DSM-III) and/or endogenous (ICD-9) depressions. After a minimum washout period of three days the patients received either 0.50 mg rolipram or 25 mg desipramine orally t.i.d. for the first three days, then 0.75 mg rolipram or 50 mg desipramine t.i.d. until day 28. Rating tests were based principally on the AMDP-system and the HAMD scale. The study showed no differences between the two drugs as regards the efficacy, but a definite trend in favour of rolipram as regards the side effects and, in particular, anticholinergic effects.

Alcohol interaction of lormetazepam, mepindolol sulphate and diazepam measured by performance on the driving simulator.

Sixteen healthy volunteers of a mean age of means = 26.4 years took part in a driving simulator test in an eightfold crossover study under double-blind conditions. The additional influence of alcohol was tested acutely after a single administration of 2 mg lormetazepam, a new, highly effective derivative from the benzodiazepine class, 10 mg mepindolol sulphate, a new betablocker without sedating properties, and 10 mg diazepam. All drugs were compared with placebo and the test was performed 1, 2 and 3 hours after oral intake. The aim was to investigate particularly the risks relevant in road traffic caused by simultaneous intake of these substances with alcohol. For this purpose, besides the driving simulator, an accurate reaction test ( WDG ) and self-rating scales were used, the latter in order to assess subjective stress and anxiety levels. Lormetazepam, due to its strong sedating property, showed a reduction in driving performance and an increase in reaction time and pulse rate as compared with placebo, and these effects were highly potentiated by alcohol. Mepindolol sulphate expectedly reduced pulse rate when compared with placebo, otherwise there were no significant differences. Diazepam, when compared with placebo, like lormetazepam caused a reduction in driving performance and reaction capacity and an increase in pulse rate, but intensity and duration of this effect were less than with lormetazepam and did not reach statistical significance. No significant potentiating effects were observed after the additional application of alcohol.

Age-specific doses of lormetazepam as a night sedative in cases of chronic sleep disturbance.

Lormetazepam, a new benzodiazepine derivative, was tested under double blind conditions in order to find the optimal dosage for different age groups of out-patients. 120 patients suffering from chronic sleep disturbance were included in the study: a younger group (age 20 to 55) and an older group (age 56 to 85 years). Four different doses were given to each age group: 0.5, 1.0, 2.0, and 3.0 mg to the younger group and 0.5, 1.0, 1.5, and 2.0 mg to the older group. A pre-placebo week (i.e. when all patients received placebo) in which baseline data were recorded preceded the two verum weeks, and these were followed by a post-placebo or withdrawal week (again all patients receiving placebo). The level of significance accepted for statistical decisions was alpha = 0.05. No differences in effects between the different doses were observed with regard to sleep pattern variables (sleep latency, sleep duration, frequency of awakenings, sleep quality, occurrence of 'bad' dreams) with the exception of sleep quality which was better in the older group than in the younger group after 0.5 mg in week 2. Considerable differences with regard to hangover feelings the next morning and during the next day (morning feelings, tranquility, alertness, and concentration), comparison of the effects of discontinuing therapy upon the above-mentioned sleep pattern variables and small differences in side effects--which were few--led to the following conclusion: --0.5 mg stood out as the best dose for the older group. --None of the dosages given to the younger group emerged clearly as superior. However, it would seem that the 1 mg dose should be the dose recommended, since fewer unfavourable scores and side effects appeared after this dose.