Alprazolam and suicidal ideation: a meta-analysis of controlled trials in the treatment of depression.

A meta-analysis of well-controlled studies of alprazolam in depression was performed to assess the possible association of alprazolam and suicidal ideation. Pooled data from 3,217 patients (alprazolam, placebo, and various active-comparative agents) who were enrolled in 22 placebo- and/or active drug-controlled depression studies were retrospectively analyzed to evaluate the emergence, worsening, and improvement of suicidal ideation during treatment with alprazolam, placebo, or other active drugs. Item 3 of the Hamilton Rating Scale for Depression was used to evaluate these events. Neither the risk of emergence nor the risk of worsening of suicidal ideation was significantly different for alprazolam than for placebo; however, alprazolam was significantly superior to placebo in producing improvement of suicidal ideation. There was no significant difference between alprazolam and the active-comparator group in the risk of emergence of suicidal ideation. The risk of worsening of suicidal ideation was significantly less for the active-comparator group (the majority of patients in this group received amitriptyline or imipramine) than for alprazolam, and improvement of suicidal ideation occurred significantly more frequently in that group than in the alprazolam group. Use of alprazolam in depressed patients is not associated with any particular increased risk of suicidality.