RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF THE EFFICACY AND TOLERABILITY OF A NEW ISOINDOLINE DERIVATIVE (DN-2327) IN GENERALIZED ANXIETY

Generalized anxiety disorders are frequent, chronic, and disabling illnesses for which so far ideal drug treatment is not available. A new promising anxiolytic drug is DN-2327, a non-benzodiazepine isoindoline derivative, which has shown in animals to have anxiolytic, taming, antiaggressive, and anticonvulsive effects without relevant sedative properties, or signs of dependence. DN-2327 showed a higher affinity for the BZ1-GABA receptor in comparison to diazepam or flunitrazepam. DN-2327 is rapidly absorbed with a tmax of 2·4 h, both after single and multiple dosing. A steady state is reached after 2–3 days of treatment. The elimination half-life is about 8 h. A first 4-week double-blind comparative study between DN-2327 and placebo was conducted in 126 patients suffering from generalized anxiety disorders, and treated as outpatients by general practitioners. The score of the Hamilton Anxiety Scale dropped significantly from baseline to week 1 with further improvement until the final visit after 4 weeks. Between-group comparisons are significant from week 1 onward. Similar results were found with the self-rating KUSTA scale. Patients treated with DN-2327 reported more unwanted events, mostly dizziness and tiredness, than patients under placebo. © 1997 John Wiley & Sons, Ltd.