An indirect comparison of the efficacy and safety of desvenlafaxine and venlafaxine using placebo as the common comparator.

BACKGROUND: This meta-analysis compared the efficacy and safety of desvenlafaxine and venlafaxine at the Australian approved doses. METHODS: A systematic literature search was conducted to identify all placebo-controlled studies of desvenlafaxine and venlafaxine in the treatment of major depression. The pivotal outcome measure used to assess comparative efficacy was the mean change in Hamilton Rating Scale for Depression-17 score from baseline. Tolerability and safety were compared by an evaluation of reported adverse events. Standard and Bayesian methods were used to conduct the indirect comparisons. Findings Using a mixed model repeated measures analysis, the pooled weighted mean difference for the mean change in Hamilton Rating Scale for Depression-17 score from baseline was -2.81 (-3.72, -1.91; p < 0.001) for desvenlafaxine and -2.61 (-3.17, -2.05; p < 0.001) for venlafaxine. An indirect Bayesian analysis adjusted for baseline Hamilton Rating Scale for Depression-17 score showed no significant difference between the two treatments (weighted mean difference -0.27; -1.17, 0.65). A standard indirect comparison of any adverse events showed no significant difference between desvenlafaxine and venlafaxine (relative risk 1.01; 0.96, 1.06; p = 0.70 and risk difference -0.01; -0.05, 0.03; p = 0.59). Standard indirect comparisons of both nausea and drop-outs identified potential differences between treatments, with the risk difference analyses suggesting a trend in favor of desvenlafaxine (nausea: relative risk 0.97; 0.77, 1.22; p = 0.80/RD -0.07; -0.12, -0.01; p = 0.02; and drop-outs due to adverse events: RR 0.86; 0.58, 1.29; p = 0.48/RD -0.04; -0.08, 0.00; p = 0.06). CONCLUSIONS: Based on the results of this meta-analysis, desvenlafaxine was shown to be non-inferior to venlafaxine in terms of efficacy, and has an advantage in terms of less nausea.

Treatment-completion rates with olanzapine long-acting injection versus risperidone long-acting injection in a 12-month, open-label treatment of schizophrenia: indirect, exploratory comparisons.

BACKGROUND: Little is known about the comparative effectiveness of atypical antipsychotics in long-acting injection formulation. Due to the absence of head-to-head studies comparing olanzapine long-acting injection and risperidone long-acting injection, this study was intended to make exploratory, indirect, cross-study comparisons between the long-acting formulations of these two atypical antipsychotics in their effectiveness in treating patients with schizophrenia. METHODS: Indirect, cross-study comparisons between olanzapine long-acting injection and risperidone long-acting injection used 12-month treatment-completion rates, because discontinuation of an antipsychotic for any cause is a recognized proxy measure of the medication's effectiveness in treating schizophrenia. Following a systematic review of the literature, two indirect comparisons were conducted using open-label, single-cohort studies in which subjects were stabilized on an antipsychotic medication before depot initiation. The first analysis compared olanzapine long-acting injection (one study) with pooled data from nine identified risperidone long-acting injection studies. The second analysis was a "sensitivity analysis," using only the most similar studies, one for olanzapine long-acting injection and one for risperidone long-acting injection, which shared near-identical study designs and involved study cohorts with near-identical patient characteristics. Pearson Chi-square tests assessed group differences on treatment-completion rates. RESULTS: Comparison of olanzapine long-acting injection data (931 patients) with the pooled data from the nine risperidone long-acting injection studies (3950 patients) provided almost identical 12-month treatment-completion rates (72.7% versus 72.4%; P = 0.87). When the two most similar studies were compared, the 12-month completion rate for olanzapine long-acting injection was significantly higher than for risperidone long-acting injection (81.3% versus 47.0%; P < 0.001). However, any conclusions drawn from this comparison may be limited by differences in the studies' geographic catchment areas. CONCLUSION: Using treatment-completion rates as a proxy measure of medication effectiveness, olanzapine long-acting injection did not differ significantly from risperidone long-acting injection when including all eligible studies. However, the findings of this exploratory analysis should be interpreted with caution, considering the methodological limitations of these indirect, cross-study comparisons.