EPP202
Efficacy and Safety of Triple Monoamine Reuptake Inhibitors for Major Depressive Disorder: Meta-analysis of Randomised Controlled Trials
Z. Kahveci 1,*, D. Karaçam 1
1Psychiaty, Istanbul University-Cerrahpşa, Istanbul, Türkiye
Introduction: Major depressive disorder (MDD) is a leading cause of disability, and current antidepressants show limited efficacy and tolerability. Triple reuptake inhibitors (TRIs; serotonin–norepinephrine–dopamine) may improve outcomes, particularly anhedonia. Several TRIs (toludesvenlafaxine, amitifadine, liafensine, GSK372475) have been tested in randomized controlled trials (RCTs), but results remain uncertain.
Objectives: To evaluate the efficacy and safety of TRIs versus placebo in adults with MDD.
Methods: Systematic searches of PubMed, Embase, and CENTRAL were conducted (Figure 1). Eligible studies were RCTs ≥6 weeks in adults with MDD, comparing TRIs to placebo/antidepressants, reporting depressive symptom scales or response/remission. Data extraction and risk-of-bias assessment were performed independently.
Results: Five RCTs met criteria. Continuous outcomes (Hedges g) showed substantial heterogeneity (Figure 3). Neutral-effect agents (amitifadine, GSK372475) pooled to SMD −0.08 [−0.37, 0.22], while toludesvenlafaxine showed large effects (Mi 2022 SMD −1.03 [−1.46, −0.60]; Mi 2023 SMD −1.90 [−2.11, −1.69]); subgroup difference significant. Tolerability was generally favorable for toludesvenlafaxine; GSK372475 showed limited efficacy and more adverse events.
Binary outcome (response; RR>1 favors TRI): pooled RR = 1.36 [0.86–2.16] (Figure 2), with high heterogeneity (I²=84.5%). Benefit was driven by toludesvenlafaxine, while other TRIs showed neutral or imprecise effects.
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Conclusions: Preliminary evidence suggests toludesvenlafaxine provides robust antidepressant efficacy with good tolerability, whereas amitifadine and GSK372475 show minimal benefit. Heterogeneity is molecule-driven. The meta-analysis is ongoing, and final pooled estimates will be presented at EPA 2026.
Disclosure of Interest: None Declared