Opipramol was developed in the 1960s as an antidepressant and has chemical similarities with tricyclic antidepressants. Pharmacodynamic properties with absent reuptake inhibition of serotonin and noradrenaline and agonism at sigma receptors distinguish opipramol from tricyclics. Furthermore, antidepressive effects are smaller than the anxiolytic ones. The mechanism of action of opipramol is currently not sufficiently understood. Agonistic effects at sigma receptors have been linked with therapeutic effects. Excessive hepatic metabolism (primarily via CYP2D6) should be considered, particularly in patients with impaired hepatic function and polypharmacy. The available clinical data suggest good tolerability and safety within the approved dose range. Mild disturbances of vigilance and anticholinergic adverse events are the predominant side effects. In Germany, opipramol is approved for the treatment of somatoform disorders and generalized anxiety disorder, and there is sufficient evidence for the efficacy of opipramol in these disorders. The agent is still prescribed very often in Germany, yet plays a minor role in the clinical as well as scientific setting. In view of the limited availability of (pharmacologic) treatment options for generalized anxiety disorder and particularly somatoform disorders, opipramol should be considered in the treatment of these entities.
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