Alprazolam vs placebo and/or tricyclic antidepressants in depression (10 double blind controlled RCTs, 2154 patients).
Alprazolam vs tricyclic antidepressants in depression (20 double blind controlled RCTs, 2930 patients).
Azapirones in major depressive disorder (3 double blind, placebo controlled RCTs studied buspirone; one studied isapirone (34 patients); one studied gepirone (130 patients); and 4 studies examined the use of drugs for primary anxiety or GAD (613 patients).
Flaws in the primary studies include heterogeneity of study sample, exclusion of patients with significant psychomotor retardation or endogenous depression, short duration of medication, high drop-out rates and absence of intention to treat analysis. No studies addressed the long term efficacy of alprazolam.
Alprazolam vs placebo in depression (10 RCTs with mean alprazolam dose from 2.4 to 3.9 mg /day, range 1.0 to 8.5 mg / day): alprazolam was superior to placebo in eight RCTs, and of equal efficacy in two RCTs.
Alprazolam vs tricyclic antidepressants in depression (20 RCTs): only one RCT demonstrated alprazolam to be significantly superior to TCA and in this study the TCA group had a significantly greater number of previous depressive episodes. Eleven of the sixteen RCTs showing alprazolam to be of equal efficacy to TCA had serious methodological flaws. Five methodologically sound studies showed alprazolam to be of equal efficacy to TCA. Three RCTs showed amytriptylline to be significantly more effective than alprazolam but flaws included exclusion of patients who had previously failed to respond to TCA and differences in prognostic indicators between treatment arms at baseline.
Azapirones in depression (2 RCTs plus 1 review that included these two studies and one other trial compared buspirone and placebo): Results from one RCT were reported to be difficult to interpret due to extremely high drop-out rates (70%). The review was not assessed for quality and showed buspirone to be significantly more effective than placebo. The authors consider that it is unclear whether the antidepressant properties of azapirone are clinically significant.
Antidepressants in generalised anxiety disorder (GAD): results were reported from one review based on 18 trials (described as usually not placebo controlled, variable with respect to sample composition, medication dosage, trial duration, and statistical rigour) and four other RCTs. The validity of the review was not assessed. One RCT (242 patients studied for 8 weeks) compared imipramine, chlordiazepoxide and placebo and found imipramine to be significantly more effective than the other therapies. One RCT (60 patients studied for 6 weeks) compared alprazolam and imipramine and found them to be of equal efficacy. One RCT (230 patients studied for 8 weeks) compared imipramine, trazodone and diazepam and found only imipramine to be significantly more effective than placebo. One RCT (81 patients studies for 8 weeks) compared paroxetine, imipramine and 2- chlordesmethyldiazepam and found there to be no statistically significant difference between treatments.