Double-blind, placebo-controlled trial of two doses of abecarnil for geriatric anxiety

We studied the tolerability and efficacy of abecarnil, a new partial benzodiazepine agonist, for short-term relief of anxiety in geriatric patients. After a 1-week placebo lead-in, 182 outpatients (mean +/- SD age = 68.3 +/- 5.8; range, 59-85 years) were randomly assigned in a double-blind, parallel-group design to high-dosage abecarnil (7.5-17.5 mg daily), low-dosage abecarnil (3.0-7.0 mg daily), or placebo for 6 weeks of acute treatment followed by abrupt discontinuation and a 2-week follow-up. During the acute treatment period, the discontinuation rate from adverse events was greater for the group treated with high-dosage abecarnil (44%) than for the groups treated with low-dosage abecarnil (14%) or placebo (12%). The most frequently reported side effects associated with abecarnil were drowsiness and insomnia. For the acute treatment period, low-dosage abecarnil was superior to placebo in reducing anxiety at Weeks 2-4 and 6, and was statistically significantly superior to high-dosage abecarnil at Weeks 4-6. More than half of the placebo group showed at least moderate global improvement at Weeks 3 and 6. One week after abrupt discontinuation of abecarnil, the placebo-treated group had less anxiety than did both groups treated with high-dosage and low-dosage abecarnil. The most commonly reported symptoms of withdrawal were headache and insomnia. These data indicate that abecarnil, at dosages ranging from 3.0 to 7.0 mg daily, is better tolerated and more efficacious for the short-term treatment of anxiety in geriatric patients than are higher dosages of 7.5 to 17.5 mg daily. Abrupt discontinuation of abecarnil at either dosage range causes definite rebound symptoms within the first week after withdrawal. These data also suggest that treatment with placebo offers at least moderate relief of anxiety in many elderly patients.