Opipramol for the treatment of generalized anxiety disorder: A placebo-controlled trial including an alprazolam-treated group

Opipramol, a drug widely prescribed in Germany, is a tricyclic compound wit h no reuptake-inhibiting properties. However, it has pronounced D-2-, 5-HT2 -, and H-1-blocking potential and high affinity to sigma receptors (sigma-1 and sigma-2). In early controlled trials, anxiolytic effects mere revealed . However, those studies were performed before the concept of generalized a nxiety disorder (GAD) was established. Because of the interesting receptor- binding profile and promising results of the early clinical trials, the aut hors performed a state-of-the-art placebo-controlled trial using alprazolam its an active control. Three hundred seven outpatients with GAD were inclu ded. After a 7-day single-blind placebo washout, patients were randomly ass igned to receive either opipramol (final dose, 200 mg/day), alprazolam (2 m g/day), or placebo and were treated for 28 days. The efficacy of both activ e compounds was higher than the effects with placebo treatment. There mere 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 improv ement of 47% for placebo and significantly more for opipramol (63%) and alp razolam (64%). Regarding safety and tolerability, no substantial difference s in the number of adverse events observed between treatment groups mere ob vious. 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 anx iolytic efficacy superior to placebo in the treatment of GAD.