Discontinuation of benzodiazepines in patients with anxiety disorders: a focus on alprazolam and alprazolam extended release

Compared with benzodiazepines that have long half-lives, those with short half-lives have been associated with a higher risk of discontinuation difficulties. The nature of the anxiety disorder for which treatment is prescribed might also have a bearing on successful medication discontinuation. In a blinded trial, the ability to discontinue treatment with the immediate-release formulation of alprazolam (alprazolam compressed tablet [CT]) was examined in 35 patients with generalized anxiety disorder (GAD) and 36 patients with panic disorder. The patients were randomized to receive adjunctive treatment with carbamazepine or placebo during discontinuation of alprazolam CT. In the placebo group, the dropout rate was significantly higher among 18 patients with panic disorder than among 17 patients with GAD. In individuals with panic disorder, the dropout rate was significantly lower among 18 patients treated with carbamazepine than in 18 patients treated with placebo. Data from 52 patients evaluated 12 to 18 months after completion of the study showed that 25% were asymptomatic and not taking any medications, 50% were taking alprazolam, and 25% were taking other medications (mostly benzodiazepines). In a double-blind trial of 215 patients with panic disorder, the mean number of weekly panic attacks after drug discontinuation was comparable among patients who had received an extended-release formulation of alprazolam (alprazolam XR) or placebo and was nonsignificantly higher among those who had received alprazolam CT. In a double-blind trial of 112 patients with GAD, physicians assessed withdrawal difficulties during discontinuation of alprazolam XR or bromazepam. Withdrawal difficulties were rated as absent in 60% of the alprazolam XR group versus 46% of the bromazepam group; mild in 20% versus 33%, respectively; moderate in 16% versus 21%, respectively; and severe in 4% versus none, respectively. Alprazolam XR provides therapeutic efficacy comparable to that of alprazolam CT, but may offer advantages during drug tapering and withdrawal.