Opipramol for the Treatment of Generalized Anxiety Disorder: A Placebo-Controlled Trial Including an Alprazolam-Treated Group

Abstract

Opipramol, a drug widely prescribed in Germany, is a tricyclic compound with no reuptake-inhibiting properties. However, it has pronounced D2-, 5-HT2-, and H1-blocking potential and high affinity to sigma receptors (sigma-1 and sigma-2). In early controlled trials, anxiolytic effects were revealed. However, those studies were performed before the concept of generalized anxiety disorder (GAD) was established. Because of the interesting receptor-binding profile and promising results of the early clinical trials, the authors performed a state-of-the-art placebo-controlled trial using alprazolam as an active control. Three hundred seven outpatients with GAD were included. After a 7-day single-blind placebo washout, patients were randomly assigned to receive either opipramol (final dose, 200 mg/day), alprazolam (2 mg/day), or placebo and were treated for 28 days. The efficacy of both active compounds was higher than the effects with placebo treatment. There were statistically significant differences (p < 0.05, according to the analysis of covariance) in the main outcome criterion (baseline-adjusted final means of an intent-to-treat analysis of the total scores on the Hamilton Rating Scale for Anxiety) and in secondary efficacy parameters, with global improvement of 47% for placebo and significantly more for opipramol (63%) and alprazolam (64%). Regarding safety and tolerability, no substantial differences in the number of adverse events observed between treatment groups were obvious. Sedation seemed more pronounced with alprazolam treatment than with opipramol or placebo. In this trial, it was demonstrated for the first time that opipramol, a strong but nonselective sigma site ligand, possesses anxiolytic efficacy superior to placebo in the treatment of GAD.

Efficacy and Tolerability of Benzodiazepines versus Antidepressants in Anxiety Disorders: A Systematic Review and Meta-Analysis

“…A total of 3 reports directly compared BDZ and TCA in patients suffering from GAD [22,23,24] (online suppl. table 1); 2 studies compared alprazolam to imipramine and opipramol, respectively [22,24] and 1 compared diazepam, imipramine and trazodone [23] (online suppl.…”

“…table 1); 2 studies compared alprazolam to imipramine and opipramol, respectively [22,24] and 1 compared diazepam, imipramine and trazodone [23] (online suppl. table 1).…”

“…When only patients with low levels of concomitant depression were considered, treatments produced a comparable effect [23]. Similarly, Möller et al [24] found no significant differences between BDZ and AD in patients with GAD.…”

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision

“…Á Alprazolam showed positive results in placeboand comparator-controlled studies (Elie and Lamontagne 1984;Enkelmann 1991;HoehnSaric et al 1988;Lydiard et al 1997;Mö ller et al 2001)(A). Á Diazepam was effective in studies containing a placebo condition (Ansseau et al 1991;Boyer and Feighner, 1993;Fontaine et al 1983;Rickels et al 1993Rickels et al , 1997Rickels et al , 2000a as well as studies using a comparator with established efficacy ( Pregabalin.…”

“…Other Medications Á Opipramol, a drug which is similar to tricyclic antidepressants with respect to chemical structure, showed efficacy in a placebo-and comparator-controlled study (Mö ller et al 2001). However, this drug is not available in many countries (B).…”