A double-blind, placebo-controlled trial of abecarnil and diazepam in the treatment of patients with generalized anxiety disorder

In a multicenter, double-blind trial, 310 patients who had received a diagn osis of generalized anxiety disorder were treated for 6 weeks with either a becarnil, diazepam, or placebo at mean daily doses of 12 mg of abecarnil or 22 mg of diazepam administered three times daily. Patients who were improv ed at 6 weeks could volunteer to continue double-blind treatment for a tota l of 24 weeks. The maintenance treatment phase allowed the comparison of ta per results for the three treatments at several study periods (0-6 weeks, 7 -12 weeks, and more than 12 weeks). Slightly more diazepam (77%) and placeb o (75%) patients completed the 6-week study than abecarnil patients (66%). At intake and baseline, after a 1-week placebo washout, the patient was req uired to have a Hamilton Rating Scale for Anxiety score of greater than or equal to 20. Major adverse events for both abecarnil and diazepam were drow siness, dizziness, fatigue, and coordination difficulties. Clinical improve ment data showed that both abecarnil and diazepam produced statistically si gnificantly more symptom relief than did placebo after 1 week of treatment. At 6 weeks treatment (using last observation carried forward analysis), ho wever, only diazepam still differed significantly (p < 0.01) from placebo. High placebo response (56% moderate to marked global improvement) at 6 week s, as well as a slightly lower nonsignificant improvement rate observed wit h abecarnil, a partial gamma-aminobutyric acid (GABA) agonist, when compare d with diazepam, a full GABA agonist, most likely contributed to our findin gs. Finally, taper results showed that only diazepam and not abecarnil caus ed the presence of temporary discontinuation symptoms, but only in patients who had been treated for at least 12 weeks.