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.

[Preliminary results of a double-blind study between rolipram and desipramine in hospitalized patients with major depressive symptoms]. / Résultats préliminaires d'une étude en double aveugle entre le rolipram et la désipramine chez des déprimés majeurs hospitalisés.

Rolipram facilitates the postsynaptic neurotransmission of NA through a completely new mechanism of action, namely, an inhibition of the inactivation of the second messenger (the cyclic AMP) by phosphodiesterase. In the present study, Rolipram is compared to a classical tricyclic antidepressant which facilitates the NA transmission through an inhibition of its presynaptic reuptake: Desipramine. Preliminary results on 12 Rolipram patients vs. 9 Desipramine patients indicate that Rolipram has an antidepressant potency comparable to Desipramine with less anticholinergic and hypotensive side effects. This study also illustrates that a 14-factor AMDP profile gives much more information than a single total score such as the Hamilton score.

[Open study of clotiazepam (Clozan) in ambulatory anxious patients centered on a multifactorial evaluation using the AMDP and on a study of the rebound effect]. / Etude ouverte du clotiazépam (Clozan) chez des patients anxieux ambulatoires centrée sur une évaluation multifactorielle par l'AMDP et sur l'étude de l'effet rebond.

The efficacy and tolerance of the first thienodiazepine, clotiazepam, is well established but its clinical spectrum and the possibility of a rebound effect upon its cessation needed further research. Moreover, the validity of the AMDP Anxiety scale had been tested but not yet its sensitivity to change. Clotiazepam was given in an "open" design to 42 anxious outpatients at the dosage of 3 X 5 to 3 X 10 mg daily during 1 month, followed by a 1-week "single blind" placebo period. No other psychotropic drug was needed in 74% of the cases. A battery of observer rating scales (CGI, VAS, HAMA, BPRS, AMDP-4 and -5, AMDP-AT) confirmed the anxiolytic and tensiolytic efficacy of clotiazepam as well as its excellent tolerance. The 13-factor AMDP profile proved superior to short scales in the sample description and in the illustration of the clinical spectrum of the drug. Both the HAMA and the AMDP-AT were sensitive to change but the HAMA more significantly than the AMDP-AT.