%0 Journal Article %A M., Dold %A L., Bartova %A R., Rupprecht %A S., Kasper %D 2017 %T Supplementary Material for: Dose Escalation of Antidepressants in Unipolar Depression: A Meta-Analysis of Double-Blind, Randomized Controlled Trials %U https://karger.figshare.com/articles/journal_contribution/Supplementary_Material_for_Dose_Escalation_of_Antidepressants_in_Unipolar_Depression_A_Meta-Analysis_of_Double-Blind_Randomized_Controlled_Trials/5401738 %R 10.6084/m9.figshare.5401738.v1 %2 https://ndownloader.figshare.com/files/9304201 %K Depression %K Antidepressants %K Treatment resistance %K Non-response %K High-dose treatment %X

Background: As many patients with unipolar depression do not respond sufficiently to initial antidepressant monotherapy, a dose increase of the current administered antidepressant (dose escalation, high-dose treatment) is frequently carried out as next treatment measure. Methods: We conducted a meta-analysis which included all double-blind randomized controlled trials (RCTs) comparing a dose increase of antidepressants directly to continuation of standard-dose treatment in unipolar depressive patients who were non- responders to standard-dose pharmacotherapy. A mean change in the Hamilton Rating Scale for Depression (HAM-D) total score was the primary outcome. Secondary outcomes were response rates and discontinuation rates due to any reason, inefficacy, and adverse effects. Hedges g and risk ratios were calculated as effect sizes. Results: Seven double-blind RCTs (8 study arms) representing 1,208 participants were included. Fluoxetine (N [number of studies] = 2, n [number of patients] = 448), sertraline (N = 2, n = 272), paroxetine (N = 2, n = 146), duloxetine (N = 1, n = 255), and maprotiline (N = 1, n = 87) were investigated. Dose escalation was not more efficacious in HAM-D total score reduction than maintaining standard-dose treatment, neither for the pooled antidepressant group (N = 7, n = 999; Hedges g = -0.04, 95% CI: -0.20 to 0.12; p = 0.63) nor the individual antidepressants. No differences could be determined for response rates, all-cause discontinuation, and drop-outs due to inefficacy. Significantly more patients in the dose escalation group dropped out due to adverse effects than in the standard-dose continuation group. The metaregressions indicate no influence of baseline symptom severity or amounts of dose increments on effect sizes. Conclusions: According to our meta-analytic findings, dose escalation after initial non-response to standard-dose pharmacotherapy cannot be regarded as general evidence-based treatment option in unipolar depression.

%I Karger Publishers