Efficacy of new-generation antidepressants assessed with the Montgomery-Asberg Depression Rating Scale, the gold standard clinician rating scale: A meta-analysis of randomised placebo-controlled trials

Abstract

BackgroundIt has been claimed that efficacy estimates based on the Hamilton Depression Rating-Scale (HDRS) underestimate antidepressants true treatment effects due to the instrument's poor psychometric properties. The aim of this study is to compare efficacy estimates based on the HDRS with the gold standard procedure, the Montgomery-Asberg Depression Rating-Scale (MADRS). Methods and findingsWe conducted a meta-analysis based on the comprehensive dataset of acute antidepressant trials provided by Cipriani et al. We included all placebo-controlled trials that reported continuous outcomes based on either the HDRS 17-item version or the MADRS. We computed standardised mean difference effect size estimates and raw score drug-placebo differences to evaluate thresholds for clinician-rated minimal improvements (clinical significance). We selected 109 trials (n = 32,399) that assessed the HDRS-17 and 28 trials (n = 11,705) that assessed the MADRS. The summary estimate (effect size) for the HDRS-17 was 0.27 (0.23 to 0.30) compared to 0.30 (0.22 to 0.38) for the MADRS. The effect size difference between HDRS-17 and MADRS was thus only 0.03 and not statistically significant according to both subgroup analysis (p = 0.47) and meta-regression (p = 0.44). Drugplacebo raw score difference was 2.07 (1.76 to 2.37) points on the HDRS-17 (threshold for minimal improvement: 7 points according to clinician-rating and 4 points according to PLOS ONE | https://doi.org/10.1371/journal.pone.0229381 February 26, 2020 1 / 11 OPEN ACCESS Citation: Hengartner MP, Jakobsen JC, Sørensen A, Plöderl M (2020) Efficacy of new-generation antidepressants assessed with the Montgomery-Asberg Depression Rating Scale, the gold standard clinician rating scale: A meta-analysis of randomised placebo-controlled trials. PLoS ONE 15(2): e0229381. https://doi.org/10.patient-rating) and 2.99 (2.24 to 3.74) points on the MADRS (threshold for minimal improvement: 8 points according to clinician-rating and 5 points according to patient-rating). ConclusionsOverall there was no meaningful difference between the HDRS-17 and the MADRS. These findings suggest that previous meta-analyses that were mostly based on the HDRS did not underestimate the drugs' true treatment effect as assessed with MADRS, the preferred outcome rating scale. Moreover, the drug-placebo differences in raw scores suggest that treatment effects are indeed marginally small and with questionable importance for the average patient.Efficacy of antidepressants based on the Montgomery-Asberg Depression Rating Scale PLOS ONE | https://doi.

Comparative efficacy of placebos in short-term antidepressant trials for major depression: a secondary meta-analysis of placebo-controlled trials

“…In accordance with previous re-analyses of the Cipriani dataset, all placebos were less effective than antidepressants (95% credible intervals [CrIs] excluding zero) [1,3,4], in line with the main results reported by Cipriani and colleagues [2].…”

“…The controversy about the clinical benefits of newgeneration antidepressants for the acute treatment of depression is ongoing and unresolved [1][2][3][4]. One major issue with antidepressant trials is that they exclusively rely on subjective outcomes, that is, clinician-ratings of depression symptoms.…”

Twelve-Month Follow-Up to a Fully Automated Internet-Based Cognitive Behavior Therapy Intervention for Rural Adults With Depression Symptoms: Single-Arm Longitudinal Study

“…Lorenzo-Luaces and colleagues’ [ 34 ] meta-analysis concluded comparable effectiveness of self-guided iCBT with that of antidepressants and in-person psychotherapy. In our trial, Thrive’s 8-week RCT between group (intervention vs control) effect size of 0.63 compared well with “mostly 8-week clinical trials of antidepressants for adults with unipolar major depression” between group (antidepressant vs placebo) effect sizes of 0.27 (Hamilton Depression Rating Scale) and 0.30 (Montgomery-Asberg Depression Rating Scale) in 109 antidepressant medication RCTs [ 35 ]. For longer-term outcomes, 12-month relapse rates from remission for Thrive at 8 weeks and STAR*D Phase I citalopram at 12 weeks [ 36 ] are 14.2% versus 33.5%, respectively.…”

Beneficial and harmful effects of antidepressants versus placebo, ‘active placebo’, or no intervention for adults with major depressive disorder: a protocol for a systematic review of published and unpublished data with meta-analyses and trial sequential analyses

“…It has been repeatedly shown that antidepressants seem to reduce depressive symptoms with a statistically significant effect, but the effect sizes are small or minimal and without importance to patients [10,29,30]. A recent review of both within patient and between patient anchor-based approaches suggested that the minimal clinically important difference on the Hamilton Depression Rating Scale 17 (HDRS-17) is likely to be in the range from 3 to 5 points [31].…”