Clonazepam in the treatment of panic disorder with or without agoraphobia: a dose-response study of efficacy, safety, and discontinuance. Clonazepam Panic Disorder Dose-Response Study Group

Abstract

In this multicenter, parallel-group, placebo-controlled, fixed-dose study, the efficacy, safety, dosing characteristics, and discontinuation of clonazepam were analyzed in patients with panic disorder. Four hundred thirteen patients were randomly assigned to receive placebo or one of five fixed daily doses of clonazepam (0.5 mg, 1.0 mg, 2.0 mg, 3.0 mg, and 4.0 mg). After 3 weeks of dose escalation, the fixed dose was given for 6 weeks (the dose-maintenance phase) and then was tapered during a 7-week discontinuance phase. The completion rates for the dose-maintenance phase ranged from 59 to 85% for the clonazepam groups (74% for the placebo group). Efficacy measurements at the end of the dose-maintenance phase indicated clinical improvement in all treatment groups but with a clear differentiation of the four higher doses of clonazepam from the 0.5-mg dose and placebo. The minimum effective dosage, as determined by the Williams' test, was 1.0 mg daily. Dose-response analysis showed that daily dosages of 1.0 mg and higher were equally efficacious in reducing the number of panic attacks. All treatments were well tolerated. Somnolence and ataxia were reported more often by patients in the 3.0- and 4.0-mg groups; depression, dizziness, fatigue, and irritability, although not showing dose-relatedness, were reported by more patients taking clonazepam than placebo. During the discontinuance phase, most patients worsened from their condition at the end of the dose-maintenance phase but did not revert to that at baseline. In addition, with the tapering schedule chosen for this study, patients in all treatment groups tolerated the discontinuance of clonazepam. Daily doses of 1.0 to 2.0 mg of clonazepam offered the best balance of therapeutic benefit and tolerability.