Drug Treatment of Anxiety: A Controlled Study of Opipramol and Chlordiazepoxide

Abstract

Following the introduction of imipramine hydrochloride as the first specific thymoleptic drug, further compounds related to the iminodibenzyl family were developed. One of these was an iminostilbene derivative with a piperazine sidechain: opipramol (Insidon, Geigy), which has the formula 4-[3-(5H-dibenzo[b,f] azepine-5-yl)-propyl]-1-(2-hydroxyethyl)-piperazine-dihydrochloride (Schindler and Blattner, 1961). The nucleus is almost identical to that of imipramine and the sidechain is identical to that of perphenazine. This compound has since been used by a number of Continental and American investigators. They have claimed thymoleptic, neuroleptic and tranquillizing properties for the drug. Some authors found an antidepressive effect inferior to that of imipramine (Schneider and Villa, 1961; Racamier, 1962); others considered it superior to imipramine in that it causes fewer side-effects and helps patients unresponsive to imipramine (Schmitt et al., 1962). Most workers mention a mild sedative effect. Donzallaz (1961) achieved most favourable results treating “psycho-autonomic disturbances”, and Hoff (1962) reported good effects on neurasthenic patients with depressive traits. All these studies were uncontrolled and, on the whole, rather impressionistic. The only blind trial known to us was done by S. R. Splitter (1963), who gave opipramol and placebo on a double-blind basis to 100 medical out-patients suffering from various disorders, with or without psychosomatic symptoms, and also exhibiting some degree of anxiety and depression. Using concomitant drug therapy as required in about half his cases, he observed excellent or good responses of target symptoms including depression, anxiety and psychosomatic complaints, as well as amelioration of any physiologic disorder in 94 per cent. of the opipramol group as against 4 per cent. in the placebo group. However Splitter's material covered a large number of divergent conditions such as adolescent behaviour problems, diabetes and cancer; they were insufficiently matched for diagnosis and apparently not at all for age.